Compositions and methods for modulating stress and uses thereof

Abstract

Disclosed herein are compositions and methods for treating, preventing, reducing, modulating, or alleviating the detrimental effects of stress, symptoms of stress, or chronic stress by providing compositions and carriers. The method may comprise, for example, administering a compound of a therapeutically effective plant extract. The compositions and methods are capable of modulating the mGlu2 and / or mGlu3 receptors.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefits of U.S. Provisional Application No. 63 / 508827, filed June 16, 2023, and U.S. Provisional Application No. 63 / 489625, filed March 10, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to compounds and compositions for regulating stress, and methods of using them. More specifically, this disclosure relates to compositions and methods for regulating stress by administering an effective amount of the composition and carrier. Background Technology

[0004] Chronic stress can harm health. Prolonged activation of the stress response system, along with excessive exposure to cortisol and other accompanying stress hormones, disrupts almost all of the body's biological processes. This increases the risk of a wide range of physical and mental health problems, including anxiety, depression, digestive issues, headaches, muscle tension and pain, heart disease, high blood pressure, stroke, sleep problems, weight gain, cancer, and impaired memory and attention. Chronic stress can also suppress the body's immune system, making it more difficult to recover from illness. Furthermore, it is estimated that 60% to 80% of primary care physician visits are related to stress, but only 3% of patients receive stress management assistance.

[0005] There are three main approaches to treating chronic stress: psychotherapy, lifestyle changes, and therapeutic interventions. While psychotherapy and lifestyle changes can effectively reduce chronic stress and its symptoms, both require significant time and effort. Therapeutic interventions typically involve anti-anxiety and antidepressant medications, including SSRIs (selective serotonin reuptake inhibitors), CNS depressants, Buspar, and beta-blockers. Unfortunately, most treatment regimens and combinations are ineffective for many patients. Furthermore, most currently approved medications require daily administration for weeks to months to achieve maximum efficacy, placing a considerable personal, psychosocial, and occupational burden on affected individuals and the healthcare system.

[0006] Furthermore, most treatments are not suitable for routine consumption as nutritional interventions or preventative measures. Traditional herbal remedies, including dietary supplements, are marketed as adjuncts to relieve stress. Examples include kava, passionflower, valerian, chamomile, lavender, and lemon balm. These products are unregulated, and the purity of their ingredients and clinical responses may vary. There is a lack of evidence to support these herbal remedies.

[0007] Clearly, there is still a need to develop a fast-acting and safe nutritional intervention to improve stress and stress-related conditions. Summary of the Invention

[0008] Some embodiments of this disclosure relate to an oral composition for treating, reducing, modulating, or alleviating the harmful effects of stress, stress symptoms, or chronic stress. The oral composition comprises a therapeutically effective amount of a plant extract, and one or more carriers or excipients, wherein the therapeutically effective amount of the plant extract is capable of treating, reducing, modulating, or alleviating the harmful effects of stress, stress symptoms, or chronic stress. In some embodiments, the plant extracts are selected from the following: rhubarb (Rheum officinale), amla (Phyllanthus emblica), apple (Malus domestica), Tripterygium wilfordii, Aloe barbadensis, cocoa (Theobroma cacao), papaya (Chaenomeles sinesis), St. John's wort (Hypericum perforatum), Satsuma mandarin orange (Citrus unshiu), lotus (Nelumbo nucifera), Acacia luederitzii, Cassia abbreviate, Cassia fistula, Colophospermumopane, Julbernardia globiflora, Habranthus brachyandrus, and macbridei (Monactis). macbridei), Acaulis, Arnica montana, Daucus carota, Bauhinia manca, Botrytis cinerea, Brosimum acutifolium, Broussonetia kazinoki, Broussonetia papyrifera, Dalbergia latifolia, Dracaena cambodiana, Dracaenadraco, Narcissus pseudonarcissus, Phanera guianensis, Rohdea chinensis, Soymida febrifuga, Taxus chinensisbrevifolia), Tupistra chinensis, Abri herba, Abrus pulchellus subsp. Cantoniensis, Achyranthes bidentata, Aconitum seravschanicum, Aconitum tasiromontanum, Acori tataninowii rhizome, Acorus gramineus, Acorus tatarinowii, Actinidia chinensis planch, Adansonia grandidieri, Aframomum giganteum, Aizopsis selkiana, Albizia myriophylla, Alisma plantago-aquatica subsp. orientale, Aloe castellorum, Aloevera, Alpiniae officinarum rhizome, Amaranthus hypochondriacus, Ampelopsis japonica, Amphorogyne spicata, Anaphalis lacteal, Anchusa azurea, Andrographis laxiflora, Andrographis neesiana, Anemarrhena asphodeloides, Apphyllocladus denticulatus, Aralia decaisneana, Artemisia annua, Artemisia parviflora, Artemisia scoparia [syn. Artemisia capillaris v, mugwort], Aspidosperma discolor, Asteris radix et rhizoma, Astragalus membranaceus, Astragalus sinicus, Atractylis lancea, Atractylodes lancea, Atractylodes ovata, Atractylodes rhizoma, Atractylodes sinensis, Atractylodes spicata, Atractylodes spicata var. integrifolia, Atractylodes spicata var. lancea, Atractylodes spicata var. sinensis, Atractylodes spicata var. thunbergii, Atractylodes spicata var. integrifolia, Atractylodes spicata var. lancea, Atractylodes spicata var. sinensis, Atractylodes spicata var. thunbergii, Atractylodes spicata var. integrifolia, Atractylodes spicata var. lancea, Atractylodes spicata var. sinensis, Atractylodes spicata var. thunbergii, Atractylodes spicata var. integrifolia, Atractylodes spicata var. lancea, Atractylodes spicata var. sinensis, Atractylodes spicata var. thunbergii, Atractylodes spicata var. integrifolia, Atractylodes spicata var. lancea, Atractylodes spicata var. sinensis, Atractylodes spicata var. thunbergii, Atractylodes spicata var. integrifolia, Atractylodes spicata var. lancea, Atractylodes spicata var. sinensis, Atractylodes spicata var. thunbergii, Atractylodes spicata var. integrifolia, Atractylodes spicata var. lancea, Atractylodes spicata var. sinensis, Atractylodes spicata var. thunbergii,rhizome), Aster sedifolius, Aster tataricus, Atadinus libanoticus, Baccharis potosina, Balanophora laxiflora, Bassia muricata, Benincasa hispida, Beta vulgaris vulgaris, Bistorta elliptica, Bistorta officinalis, Boehmeriae rhizoma et radix, Boehmeria nivea, Boehmeria platanifolia [synonym: Boehmeria tricuspis, platanifolia], Bolbostemae paniculati bulbus, Bolbostemma paniculatum, Brassica rapa, Bridelia stipularis, Canarium bengalense, Carduus tenuiflorus, Cascarasagrada, Cassia alata L., Cassia angolensis, Cassiae semen, Cassia fastuosa, Cassia javanica, Cassia obtusifolia, Cassia occidentalis, Cassia speciosa, Cassia tora L., Cassia tora, Cassia torosa L., Catalpa longissima, Caulerpa peltata, Caulis Polygoni Multiflori, Caulis Sargentodoxae, Caulocystis cephalornithos, Cephaelisipecacuanha, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis, Cephalotaxus fortunei, Cephalotaxus oliveri, Cephalotaxus sinensis,griffithii), Chaiturus marrubiastrum, Chamaecrista mimosoides, Chamaecrista nigricans, Chamaecrista nomame, Chamaecrista pumila, Cheilanthes argentea, Chenopodium quinoa, Cichorium intybus, Cirsium oligophyllum, Clibadium sprucei, Coreopsis tinctoria, Corydalis rhizoma, Cranfillia fluviatilis, Cratoxylum formosum, Cremastra appendiculata, Cynanchum viminale, Dalbergia hupeana, Dalbergia lanceolaria subsp. paniculata, Degenia velebitica, Delphinium nuttallianum, Delphinium virgatum, Dendriopoterium menendezii, Dendrobium thyrsiflorum, Derris canarensis, Derris cuneifolia, Derris oblonga, Dianthi herba, Dianthus caryophyllus, Dictyopteris australis, Dillenia indica, Dioscoreae bulbiferae, Dipsacus azureus, Dodonaea viscosa, Dysoxylum cumingianum, Dysoxylum muelleri, Elymus repens, Enceliopsisargophylla, endophyticaspergillus, Epimedium koreanum, Epimedium herba, Eria mollis, Eriocaulon buergerianum, Eriocaulon sieboldianum, Erythrina lysistemon, Erythrophleum ivorense, Euodia bodinieri, Euodia officinalis, Euodia ruticarpa, Fagopyrum esculentum, Fagopyrum tataricum, Fallopia multiflora, Fallopia sachalinensis, Flacourtia jangomas, Frangula alnus, Frangula purshiana, Fridericia triplinervia, Garcinia polyantha, Gleichenia quadripartita, Glycyrrhiza uralensis, Gnaphalii affinis herba, Grangea maderaspatana, Hedera helix, Helichrysum chionosphaerum, Helichrysum plicatum, Heynea trijuga, Hoveniae dulcissemen, Hymenoxys lemmonii, Hypericum prolificum, Hypericum sampsonii, Isatdis radix, Isatis tinctoria, Jacquemontia paniculate, Juniperus ashei, Juniperus chinensis, Juniperus communis, Juniperus procera, Juniperus rigida, Juniperus sabiniana, Juniperus squamata, Juniperus virginiana, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalimeris indica, Kalformosana), Justicia secunda, Lactuca plumieri, Lactuca sativa, Lanaria lanata, Larix kaempferior, Lavandula vera, Leptocereus quadricostatus, Lespedeza tomentosa, Ligularia pleurocaulis, Lilii bulbus, Lilium brownii f. e. brown var. colchesteri wils, Lilium brownii var. viridulum [syn. Lilium brown, Lilium brownii var. viridulum], Lobelia berlandieri, Loranthus pentandrus, Lupinus corymbosus, Lycii cortex, Maclura tinctoria, Magnolia figo, Magnolia ovata, Mandragora autumnalis, Melicope triphylla, Mentha arvensis, Menthacanadensis, Menthae herba, Metrodorea nigra, Miliusa velutina, Mitracarpus scaber, Muehlenbeckia tamnifolia, Muntingia calabura, Myrsine africana, Nekemias grossedentata, Neobalanocarpus heimii, Nepeta granatensis, Nepeta laricifolia, Nidus indicus, Nitraria sibirica, Nymphaea tetragona, Ochna serrulata, Oenothera rosea, Olea europaea subsp. cuspidata, Olea europaea subsp. sylvestris, Ononis spinosa, Oplopanax elatus, Opuntia vulgaris, Origanum vulgare, Osmorhiza aristata, Osmoxylon lineare, Oxalis pes-caprae, Oxyceros ruber, Pachysandra terminalis, Paeonia suffruticosa, Paliurus spurius, Panicum maximum, Panicum virgatum, Papaver somniferum, Parthenocissus tricuspidata, Passiflora incarnata, Passiflora tarminiana, Patrinia scabiosaaefolia, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, Pedilanthus pavonis, PedilParnassica), Nuxia floribunda, Onobrychis arenaria, Oryctes monoceros, Osmanthus armatus, Passiflora sexflora, Persicaria decipiens, Persicaria hydropiper, Persicaria maculosa, Persicaria perfoliata, Persicaria salicifolia, Petunia integrifolia subsp. inflata, Phaseolus vulgaris, Phlogacanthus curviflorus, Photinia serratifolia, Physalis alkekengi, Picramnia antidesma, Picramnia hirsuta, Picramnia teapensis, Picramnia teapensis Tul., Picrasma quassioides, Pinalia stricta, Pisum sativum, Plantago coronopus, Plantago lanceolata, Pleione bulbocodioides, Pleione yunnanensis, Ploiarium alternifolium, Pluchea odora, Pneumatopteris pennigera, Polygoni cuspidati rhizoma et radix, Polygonum cuspidatum, Polygonum hypoleucum, Polygonum multiflorum, Polygonum perfoliatum, Polygonum tinctorium, Polypodium vulgare, Polystichum aculeatum, Polystichum braunii, Polystichum caliginum, Polystichum lonchitis, Polystichum luctuosum, Polystichum tsus-siense, Polystichum tsus-siense var. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichum tsus-siense var. tsus-siense f. tsus-siense, Polystichummultiflorum), Polygonum perfoliatum, Pseudolarix amabilis, Psorospermum glaberrimum, Psorospermum laurentii, Psorospermum tenuifolium, Psychotria stachyoides, Quercus rubra, Radix Boehmeriae, Radix et Rhizoma Rhei, Radix et Rhizoma Rhei Praeparata, Ravenia spectabilis, Reynoutria japonica, Rhamnus cathartica, Rhamnus davurica, Rhamnus erythroxyloides, Rhamnus formosana, Rhamnus frangula [Syn. Frangula alnus], Rhamnus frangula, Rhamnus hirtella, Rhamnus kurdica, Rhamnus nakaharae, Rhamnus nepalensis, Rhamnus pallasii, Rhamnus prinoides, Rhamnus procumbens, Rhamnus punctata, Rhamnus saxatilis, Rhamnus thymifolius, Rhamnus triquetra, Rhamnus wightii, Rheum acuminatum, Rheum alexandrae, Rheum altaicum, Rheum nobile, Rheum officinale, Rheum palmatum, Rheum rhubarbarium, Rheum webbianum, Rhodotypos umbellata, Rhodotypos vitifolium, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uva-crispa, Rhodotypos uRheum australe, Rheum compactum, Rheum coreanum, Rheum delavayi, Rheum emodi [synonym: Rheum australe], Rheum franzenbachii, Rheum hotaoense, Rheum inopinatum, Rheum kialense, Rheum likiangense, Rheum nanum, Rheum nobile, Rheum palmatum, Rheum pumilum, Rheum racemiferum, Rheum reticulatum, Rheum rhabarbarum, Rheum rhaponticum, Rheum currantum Rhubarb ribes), Rheum spiciforme, Rheum spp., Rheum subacaule, Rheum sublanceolatum, Rheum tanguticum, Rheum tataricum, Rheum undulatum, Rheum uninerve, Rheum wittrockii, Rheum wittrocki, Rheum yunnanense, Rhizoma fagopyri cymose, Rhodiola viridula, Rhododendron dahuricum, Rosapomifera, Rumex abyssinicus, Rumex acetosa Sorrel (Rumex acetosella), Sorrel (Rumex aegyptiacus), Sorrel (Rumex alpinus), Sorrel (Rumex bequaertii), Sorrel (Rumex chalepensis), Sorrel (Rumex scabra)Rumex crispus, Rumex cristatus, Rumex cyprius, Rumex dentatus, Rumex japonicus, Rumex lanceolatus, Rumex limoniastrum, Rumex nepalensis, Rumex patientia, Rumex pictus, Rumex pulcher, Rumex ruwenzoriensis, Rumex scutatus, Rumex simpliciflorus, Rumex spp., Rumex tuberosus, Rumex usambarensis, Rumex vesicarius, Salvia aurea, Salvia greggii, Sargentodoxa cuneata, Sargentodoxae caulis, Saururus chinensis, Schistostephium artemisiifolium, Scilla socialis, Selaginella labordei, Semen pharbitidis, Senecio behnii, Senecio bonariensis, Senecio praecox, Senecio subdentatus, Senna alata, Senna alexandrina, Senna angustisiliqua, Senna artemisioides, Senna auriculata, Senna candicans, Senna curranii, Senna didymobotrya, Senna flavens, Senna hirsuta, Senna lindheimeri, Senna macra, Senna multiglandulosa, Senna occidentalis, Senna pendulinoides, Senna surattensis, Senna tora, Senna torosa, Senna xalapensis, Senna zanzibarica, Senna zeylanica, Serjania chamaecarpa, Serjania cordifolia, Serjania domingensis, Serjania ferruginea, Serjania glomerata, Serjania guineensis, Serjania hirta, Serjania humulifolia, Serjania jamaicensis, Serjania latifolia, Serjania leucantha, Serjania ligustrina, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, Serjania lucida, SerCorymbosa), Senna didymobotrya, Sennae folium, Senna lindheimeriana, Senna macranthera, Senna obtusifolia, Senna occidentalis, Senna petersiana, Senna podocarpa, Senna septemtrionalis, Senna siamea, Senna sophera, Senna spectabilis, Senna tora, Simaba orinocensis, Smythea bombaiensis, Solanum cleistogamum, Sophorae tonkinensis radix et rhizome, Spatholobus suberectus, Sphaerella rosigena, Spinacia oleracea, Stevia berlandieri, Stevia ovata, Syzygium australe, Tagetes filifolia, Tanacetum coccineum, Taraxacum kok-saghyz, Taraxacum platycarpum subsp. hondoense, Tetradium ruticarpum, Teucrium yemense, Thymelaea hirsute, Tribuli fructus, Tribulus terrestris, Uvaria afzelii, Vatairea heteropteran, Ventilago maderaspatana, Viscum album, Viscum articulatum, Viscum minimum, Viscum ovalifolium, Viscum orientale, Viscum ovalifolium, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Viscum ovalis, Visccalyculata), Ventilago denticulata, Ventilago leiocarpa, Ventilago madraspatana, Verbascum thapsiforme, Vismia guianensis, Vismia guineensis, Vismia laurentii, Vismia orientalis, Vitis vinifera, Wilbrandia ebracteata, Xanthii fructus, Xerochrysum viscosum, Angelica archangelica, Frangula purshiana, Geranium maculatum, Rumex crispus, Senecio congestus, Senna alexandrina, Aloe africana, Aloe arborescens, Aloe castellorum, Aloe elgonica, Aloe ferox, Aloe rubroviolacea, Aloe spicata, Aloe succotrina, Asphodeline tenuior, Asphodelus aestivalis, Asphodelus albus, Asphodelus fistulosus, Asphodelus ramosus, Asphodelus tenuifolius, Berchemia floribunda, Bergenia hissarica, Bulbine annua, Bulbine asphodeloides, Callisia fragrans, Cassia aldabrensis, Cassia occidentalis, Cassia surattensis, Cassia torosa, Cassia torulosa, Cassia vohemarum, Cassia wilsoniana, Cassia xanthomyria, Cassia xanthophylla, Cassia xanthotricha, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassia xiphioides, Cassiagrandis), Cassia javanica, Chamaecrista mimosoides, Commiphora socotrana, Frangula alnus, Frangula purshiana, Kniphofia ensifolia, Kniphofia foliosa, Kniphofia insignis, Kniphofia isoetifolia, Kniphofia schimperi, Picramnia antidesma, Picramnia hirsute, Psidium guajava, Reynoutria japonica, Rhamnus alaternus, Rhamnus cathartica, Rhamnus davurica, Rheum acuminatum, Rheum alexandrae, Rheum altaicum, Rheum australe, Rheum compactum, Rheum coreanum, Rheum delavayi, Rheum franzenbachii, Rheum hotaoense, Rheum inopinatum, Rheum kialense, Rheum likiangense, Rheum nobile, Rheum palmatum, Rheum pumilum, Rheum racemiferum, Rheum reticulatum, Rheum rhabarbarum, Rheum rhaponticum, Rheum ribes, Rheum spiciforme, Rheum subacaule, Rheum webbianum, Rheum xizangense, Rheum xunhuaense, Rhus coriaria, Rhus succedaneum, Rhus triphylla, Rhus verniciflua, Rhus wallichiana, Rhus xizangensis, Rhus yunnanensis, Rhus zambal, Rhus zanthoxyloides, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, Rhus zippeliana, RRheum tanguticum, Rheum tataricum, Rheum undulatum, Rheum uninerve, Rheum wittrockii, Rheum yunnanense, Rumex cristatus, Rumex paulsenianus, Rumex scutatus, Selaginella delicatula, Senna alata, Senna alexandrina, Senna didymobotrya, Senna obtusifolia, Senna occidentalis, Senna petersiana, Senna reticulata, Senna siamea, Senna tora, Spatholobus suberectus, Stephania dinklagei, Xanthorrhoea australis, Cichorium intybus, Cassia occidentalis, Morinda royoc, Galium aparine, Bryophyllum pinnatum, Anthema tinctoria, Aegle marmelos, Cymbopogon spp, Wedelia trilobata, Angelica archangelica, Vitis tilifolia, Mirabilis jalapa, Centipeda minima, Bauhinia manca, Juniperus drupacea, Forsythia suspensa, Citrus sinensis, Hylocomium splendens, Carthamus tinctorius, Rosmarinus officinalis, Oryza sativa,sativa), red clover (Trifolium pratense cv. Redman), barley (Hordeum vulgare cv. Seco), N. x hookeriana, M. acuminata, Douglas-fir (Pseudotsuga menziesii var. menziesii), cocoa, barley (Hordeum vulgare cv. Seco), N. x hookeriana, M. acuminata, Douglas-fir (Pseudotsuga menziesii var. menziesii), S. officinalis, pea, soybean, oat, apple, gardenia, A. millenii, rice, C. arabica, Safflower, V. unguiculata, Solanum, Citrus unshiu, H. perforatum, C. longa, Nypa fruticans, S. cereale cv. Aroostook, Polygonum, Cannabis, tomato, C. clementina, Trifolium pratense cv. Redman, Uncaria tomentosa, Auricularia judaica, C. sinensis, Cycas, Momordica charantia, Erysimum cheirii, Nelumbo nucifera, Raphanus sativus var. niger, Raphanus sativus var. radicula, Zea mays, Nicotiana tabacum, Agaricus subrufescens, Linum usitatissimum, Paeonia, Capsicum annuum, Distylium myricoides, Jasminum officinale, Catharanthus roseus, Medicago sativa subsp. sativa, Solanum nigrum, C. arabica, Momordica charantia, S. grandiflorum, C. cacao, A. millenii, Gardenia, Cashew, Capsicum annuum, Paeonia, C. clementina, Hordeum vulgare, Erucastrum gallicum, Linum usitatissimum, Asclepias syriaca, Avena sativa, H. perforatum, C. longa, Zea mays, Eucalyptus bisecta, M. acuminata, Solanum, Phyllanthus emblica, Lycium barbarum, Solanum lycopersicum, Veronica, Malva sylvestris, Hymenaea courbaril, Pseudotsuga menziesii var. menziesii, Podocarpus spicatus, Tripterygium wilfordii, Spatholobus suberectus, Crinum moorei, Juniperus chinensis, Piptoporus betulinus, Gypsophila perfoliate, Clausena excavata, Gynura formosana, Trifolium pratense, Oryza sativa, Rosmarinus officinalis, Nelumbo nucifera, Safflower, Citrus unshiu, Physcomitrella, Citrus sinensis, Juniperus coniana, H. perforatum, Momordica charantia, S. grandiflorum, C. cacao, A. millenii, C. clementina, Hordeum vulgare, Erucastrumgallicum, flax, Eupatorium syriacum, Hypericum perforatum, Larrea tridentata, Eucalyptus globulus subsp. bicostata, Phyllanthus emblica, Veronica polita, Alcea rosea, Neolamarckia cadamba, Catharanthus roseus, Podocarpus spicatus, Tripterygium wilfordii, Juniperus monosperma, Pleurotus ostreatus, Gypsophila perfoliate, Clausena excavate, Gynura procumbens, Trifolium pratense cv. Redman, Rosmarinus officinalis, Nelumbo nucifera, Citrus unshiu, Dicranum scoparium, Citrus sinensis, Juniperus drupacea, Forsythia suspensa, or a combination thereof. In some embodiments, the plant extract comprises a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloe-emodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazuleno[6,5-b]furan-4-yl methyl acrylate, or a combination thereof. In some embodiments, the oral composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutraceutical, or a pharmaceutical composition. In some embodiments, the dosage form of the oral composition is configured as one of a soft gel capsule, a hard gel capsule, a liquid, a powder, and a tablet. In some embodiments, the oral composition comprises 10% to 99% w / w of the plant extract. In some embodiments, the plant extract further comprises a preservative. In some embodiments, the plant extract further comprises a sweetener. In some embodiments, the plant extract further comprises a colorant. In some embodiments, the plant extract further comprises an additive. In some embodiments, the plant extract further comprises a flavoring agent.

[0009] Some embodiments relate to a method of treating, preventing, reducing, modulating, or alleviating stress, a symptom of stress, or a deleterious effect of chronic stress in a subject in need thereof. In some embodiments, the method comprises administering a therapeutically effective amount of a composition, including an oral composition described herein. In some embodiments, the plant extract of the oral composition is capable of activating a metabotropic receptor type II. In some embodiments, the plant extract activates the mGlu2 receptor. In some embodiments, the plant extract activates the mGlu3 receptor. BRIEF DESCRIPTION OF DRAWINGS

[0010] Figure 1 Graphs depicting plant fractions with demonstrated antagonistic / inhibitory activity are shown.

[0011] Figure 2 Graphs depicting plant fractions with demonstrated agonistic / activating activity are shown.

[0012] Figure 3 Flowcharts depicting standardized bioassay protocols are shown.

[0013] Figure 4 Bar graphs showing mGluR2 antagonist / NAM assay activity are shown.

[0014] Figure 5 Bar graphs showing mGluR2 antagonist / PAM assay activity are shown. DETAILED DESCRIPTION

[0015] The present disclosure provides, among other things, compounds, compositions, including oral compositions, and methods of administering the compounds and compositions to modulate or treat stress or a symptom or condition associated with stress. In some embodiments, the oral compositions comprise a therapeutically effective amount of a compound or plant extract and one or more carriers or excipients. In some embodiments, a method of treating, preventing, reducing, modulating, or alleviating stress, a symptom of stress, or a deleterious effect of chronic stress in a subject comprises administering a composition described herein. The present disclosure also provides, among other things, oral compositions and methods of administering the compositions orally to modulate one or more metabotropic glutamate receptors type II. In some embodiments, a compound, plant extract, or composition described herein is a positive allosteric modulator (PAM) of metabotropic glutamate receptors type II. In some embodiments, a compound, plant extract, or composition described herein is an antagonist of one or more metabotropic glutamate receptors type II. In some embodiments, a compound, plant extract, or composition described herein is an agonist of one or more metabotropic glutamate receptors type II.

[0016] Compositions

[0017] In some aspects, the present disclosure provides a composition comprising a plant extract and a carrier. In some embodiments, the composition is an oral composition. As used herein, "extract" refers to a composition containing a desired compound of interest that is separated from other substances present in the natural source material from which the oral composition is obtained. The plant extract can be obtained from any plant tissue, including: whole plants; plant parts, such as shoot vegetative organs / structures (e.g., leaves, stems and tubers), roots, flowers, and floral organs / structures (e.g., bracts, sepals, petals, stamens, carpels, anthers, and ovules), seeds (including embryos, endosperms, and seed coats), and fruits (maturation ovaries); plant tissues (e.g., vascular tissues, root tissues, etc.); or cells (e.g., guard cells, egg cells, etc.), as well as progeny and cultures or cell lines thereof. In some embodiments, the extract is generally recognized as safe for human consumption. Thus, in certain embodiments, the extract is from an edible source. In this regard, the extract is an edible extract. The extract can be prepared by freezing, grinding, macerating, pulverizing, and / or fermenting the source material of interest, solvent extraction of the source material, and separating insoluble material from soluble material. In this regard, the "extract" of the present disclosure can be crude, fractionated, sub-fractionated, separated, isolated, enriched, or purified, but is not limited thereto.

[0018] In some embodiments, the plant extract can be a crude extract. As used herein, "crude" refers to a compound or molecule that has not been completely separated from the components of the original composition in which it is found. In embodiments involving fractions or sub-fractions, molecules in a crude extract can be partially separated to provide a less crude extract containing other substances. In contrast, the term "isolated" refers to a compound or molecule that is sufficiently enriched or purified relative to its naturally occurring complex cellular environment (e.g., a crude extract). When an isolated molecule is enriched or purified, the absolute level of purity is not critical, and one of skill in the art can readily determine an appropriate level of purity depending on the use of the material. In some cases, the isolated molecule constitutes a part of a composition (e.g., an extract that is more or less crude containing many other substances), which can, for example, contain other components. In other cases, the isolated molecule can be purified to be substantially homogenous, for example, as determined by spectrophotometry, NMR, or chromatography (e.g., LC-MS).

[0019] Suitable solvents for preparing the extract include, for example, n-pentane, hexane, butane, chloroform, dichloromethane, diethyl ether, acetonitrile, water, butanol, isopropanol, ethanol, methanol, glacial acetic acid, acetone, norflurane (HFA 134a), ethyl acetate, dimethyl sulfoxide, heptafluoropropane (HFA 227), and subcritical or supercritical fluids such as liquid carbon dioxide and water, or combinations thereof in any ratio. When using the above solvents, the resulting extract typically contains non-specific lipid-soluble material. This can be removed by a variety of processes, including "winterization," which involves cooling to a specific temperature, typically -20 °C, followed by filtration or centrifugation to remove waxy material, extraction with subcritical or supercritical carbon dioxide or non-polar solvents (e.g., hexane), and distillation.

[0020] In some embodiments, the plant extract may be selected from the following: rhubarb, amla, apple, tripterygium wilfordii, aloe barbadensis, cocoa, papaya, St. John's wort, Citrus unshiu, lotus, Acacia luederitzii, Cassia abbreviate, Cassia, Cassia fistula, Julbernardia globiflora, Habranthus brachyandrus, Monactis macbridei, Arnica acaulis, arnica, carrot, Bauhinia manca, Botrytis cinerea, Brosimum acutifolium, Broussonetia kazinoki, Broussonetia Papyrifera, Dalbergia latifolia, Dracaena cochinchinensis, Dracaena spp., Daffodil, Phanera guianensis, Rohdea chinensis, Soymida febrifuga, Taxus chinensis, Tupistra chinensis, Abrus precatorius, Abrus reticulata, Achyranthes bidentata, Aconitum seravschanicum, Aconitum tasiromontanum, Acorus calamus rhizome, Acorus calamus, Acorus calamus, Actinidia chinensis, Baboon fern, Aframomum giganteum, Aizopsis selkiana, Albizia julibrissin, Alisma plantago-aquatica, Aloe castellorum, Alpinia galanga, Alternanthera philoxeroides, Amphora spicata, Anaphalis spp. lacteal), ox tongue grass, Andrographis laxiflora, Andrographis neesiana, Anemarrhena, Aphyllocladus denticulatus, Aralia elataArtemisia decaisneana), Artemisia annua, Artemisia serrata, Artemisia capillaris [synonyms: Artemisia capillaris, Artemisia capillaris], Artemisia heterophylla, Asteris radix et rhizome, Astersedifolius, Aster, Atadinus libanoticus, Baccharis potosina, Balanophora laxiflora, Bassia muricata, winter melon, beet, Polygonum elliptica, Polygonum bistorta, ramie rhizome and root, ramie, ramie [synonyms: ramie, ramie], Bolbostema epaniculati bulbus, ramie, turnip, sagebrush, calendula, Carduus tenuiflorus, Cascara sagrada, Cassia alata L.), Cassia angolensis, Cassia seeds, Cassia fastuosa, Javanese sausage tree, Cassia obtuse-leaved, Sennaoccidentalis, Cassia speciosa, Cassia tora L., Cassia (Cassiatora), Cassia torosa L., Catalpa longissima, Shield-leaved fern, Polygonum multiflorum vine, Sargentodoxa cuneata, Caulocystis cephalornithos, Cephaelis ipecacuanha, Cephalotaxus fortunei, *Cyperus rotundus*, *Mimosa pudica*, *Chamaecrista nigricans ... fluviatilis), Vietnamese yellow cowwood, azalea, long-stemmed flesh coral, rosewood, lanceolate rosewood subspecies paniculata, Degenia velebitica, nuttallianum (Delphinium nuttallianum), upright larkspur (Delphinium virgatum), Dendriopoterium menendezii, globe flower dendrobium, orchid vine (Derris canarensis), false vine, orchid vine (Derris canarensis)(The remaining text appears to be a list of unrelated words and phrases, possibly from different sources. A direct translation wouldn't be meaningful.) Triplelinervia, Garcinia polyantha, Gleichenia quadripartita, Licorice, Gnaphalium affine, Lysimachia christinae, Hedera helix, Helichrysum chionosphaerum, Helichrysum plicatum, Partridge flower, Hoveniae dulcis semen, Hymenoxys lemmonii, Hypericum sampsonii, Isatis indigotica, Isatis tinctoria, Morning glory, Juniperus chinensis, Justicia secunda, Lactuca plumieri, Lettuce, Lanaria edelweiss lanata), Japanese larch, lavender, small brown columnar (Leptocereus quadricostatus), velvety lespedeza, lateral stem ligustrum, lily (Lilii bulbus), wild lily (Lilium browniif. e. brown var. colchesteri wils), lily (Lilium brownii var. viridulum) [Synonyms: wild lily (Lilium brown), lily (Lilium brownii)]var. viridulum)], Lobelia berlandieri, Taxillus quinquefolius, Lupinus corymbosus, Canavalia cathartica, Maclura tinctoria, Michelia alba, Magnolia ovata, Mandragora autumnalis, Melicope triphylla, Mentha arvensis, Mentha canadensis, Menthae herba, Metrodorea nigra, Osmorhiza aristata, Mitracarpus scaber, Muehlenbeckia tamnifolia, Myrsine africana, Myrsine stellata, Neobalanocarpus heimii, Nepeta granatensis, Nepeta parnassica, Nuxia floribunda, Onobrychis arenaria, Oryctes monoceros, Osmanthus heterophyllus, Passiflora sexflora, Persicaria decipiens, Polygonum hydropiper, Polygonum orientale, Polygonum perfoliatum, Persicaria salicifolia, Petunia integrifolia subsp. inflata, Phaseolus vulgaris, Plumeria acutifolia, Photinia fraseri, Physalis pruinosa, Picramnia antidesma, Picramnia hirsuta, Picramnia teapensis, Picramnia teapensis Tul., Picrasma quassioides, Platanthera bifolia, Pisum sativum, Plantago lanceolata, Plantago major, Pleione bulbocodioides, Pleione grandis, Ploiarium alternifolium, Pluchea odora, Pneumatopteris pennigera,Pennisetum setosum, Polygonum cuspidatum rhizome and root, Polygonum cuspidatum, Polygonum hypoleucum, Polygonum multiflorum, Polygonum perfoliatum, Pinus densata, Psorospermum glaberrimum, Psorospermum laurentii, Psorospermum tenuifolium, Psychotria stachyoides, Quercus aliena, Ramie root, Rheum officinale, Rheum officinale (stir-baked), Ravenia spectabilis, Reynoutria japonica, Rhamnus cathartica, Rhamnus davurica, Rhamnus erythroxyloides, Rhamnus formosana, Rhamnus frangula [Synonym: Frangula alnus], Rhamnus frangula, Rhamnus hirtella, Rhamnus kurdica, Rhamnus nakaharae, Rhamnus nepalensis, Rhamnus pallasii, Rhamnus purpurea, Rhamnus saxatilis, Rhamnus thymifolius, Rhamnus triquetra, Rhamnus wightii, Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum officinale, Rheum officinale (stir-baked), Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stir-baked), Rheum coreanum, Rheum emodi, Rheum emodi [Synonym: Rheum austale], Rheum palmatum, Rheum palmatum (stir-baked), Rheum rhabarbarum, Rheum rhabarbarum (stir-baked), Rheum webbianum, Rheum webbianum (stirRhubarb franzenbachii), Rhubarb of Hetao, Rhubarb with red veins, Rhubarb of sparse branches, Rhubarb of Lijiang, Rhubarb dwarf, Rhubarb of tower, Rhubarb with palmate leaves, Rhubarb sparse, Rhubarb of totality, Rhubarb with reticulate veins, Rhubarb with wavy leaves, Rhubarb for consumption, Rhubarb of gooseberry fruit, Rhubarb of spikes, Rhubarb spp., Rhubarb of weeping branches, Rhubarb of narrow leaves, Rhubarb of chicken claw, Rhubarb of round leaves, Rhubarb of wavy leaves (Rheum undulatum), Rhubarb with single veins, Rhubarb of Tianshan, Rhubarb of Tianshan, Rhubarb of Yunnan, Fagopyrum cymosum, Rhodiola viridula, Rhododendron dahuricum, Rosae (Rosa pomifera), Abyssinicus, Rumex acetosa, Rumex acetosella, Aegyptiacus (Rumex Rumex bequaertii, Rumex bequaertii, Rumex reticulata, Rumex cristatus, Rumex cyprius, Rumex dentata, Rumex lanceolatus, Rumex limoniastrum, Rumex nigra, Rumex patina, Rumex pictus, Rumex pulcher, Rumex ruwenzoriensis, Rumex scutatus, Rumex simpliciflorus, Rumex spp., Rumex tuberosus, Rumex usambarensis, Rumex bladder Sage (Salvia greggii), *Sargentodoxa cuneata*, *Sargentodoxaecaulis*, *Salvia variegata*, *Schistostephium artemisiifolium*, *Scilla socialis*, *Selaginella tamariscina*, *Morning Glory*, *Senecio*Aloysia citriodora, Aloysia gratiosa, Aloysia recemosa, Aloysia virgata, Alpinia speciosa, Alpinia zerumbet, Alstroemeria aurantiaca, Alstroemeria pelegrina, Alstroemeria revoluta, Alstroemeria versicolor, Alstroemeria x hybrida, Amaranthus dubius, Amaranthus hypochondriacus, Amaranthus palmeri, Amaranthus paniculatus, Amaranthus retroflexus, Amaranthus thunbergii, Amaranthus viridis, Amaranthus xanthioides, Ambrosia artemisiifolia, Ambrosia artemisioides, Ambrosia cumanensis, Ambrosia hispida, Ambrosia peruviana, Ambrosia psilostachya, Ambrosia siccanea, Ambrosia trifida, Ambrosia x hybrida, Amelanchier alnifolia, Amelanchier canadensis, Amelanchier laevis, Amelanchier lamarckii, Amelanchier ovalis, Amelanchier x grandiflora, Ammopiptanthus mongolicus, Amorpha fruticosa, Amorpha x intermedia, Anacardium occidentale, Anadenanthera colubrina, Anadenanthera falcata, Anadenanthera x intermedia, Anagallis arvensis, Anagallis minima, Anagallis tenella, Anaxagorea acutata, Anaxagorea annulata, Anaxagorea x intermedia, Anemone nemorosa, Anemone sylvestris, Anemone x hybrida, Anethum graveolens, Aniba rosaeodora, Anisomeles indica, Anisomeles x intermedia, Anisomelia indica, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeles x intermedia, Anisomeebracteata, Xerochrysum viscosum, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chrysanthemum coronarium, Chsuberectus), Butea frondosa, Eucalyptus citriodora, Endive, Senna occidentalis, Morinda royoc, Lysimachia clethroides, Rafflesia zollingeri, Anthema tinctoria, Melia toosendan, Cymbopogon nardus, Wedelia trilobata, Daucus carota, Vitis caribaea, Plumbago indica, Bauhinia manca, Juniperus polycarpos, Hypericum perforatum, Citrus sinensis, Hypnum plumaeforme, Crocus sativus, Rosmarinus officinalis, Oryza sativa, Trifolium pratense cv. Redman, Hordeum vulgare cv. Seco, Nepenthes hackettii, Musa acuminata subsp. malaccensis, Pseudotsuga menziesii var. menziesii, Theobroma cacao, Hordeum vulgare cv. Seco, Nepenthes hackettii, Musa acuminata subsp. malaccensis, Pseudotsuga menziesii var. menziesii, Salvia rosmifolia, Pisum sativum, Glycine max, Avena sativa, Malus domestica, Gardenia jasminoides, Aloe ferox, Oryza sativa, Coffea canephora, Crocus sativus, Macrotyloma uniflorum, Solanum lycopersicum, Citrus clementina, Trifolium pratense cv. Redman, Uncaria tomentosa, Judaea anatina, Citrus sinensis, Cycas revoluta, Momordica charantia, Eruca vesicaria, Nelumbo nucifera, Raphanus sativus var. niger, Daucus carota, Zea mays, Nicotiana tabacum, Laccaria laccata, Linum usitatissimum, Paeonia officinalis, Capsicum annuum, Tabernaemontana divaricata, Vicia hirsuta, Coffea canephora, Momordica charantia, Silybum marianum, Theobroma cacao, Gardenia jasminoides, Anacardium occidentale, Capsicum annuum, Paeonia officinalis, Citrus clementina, Hordeum vulgare, Erucastrum gallicum, Linum usitatissimum, Asclepias syriaca, Avena sativa, Hypericum perforatum, Curcuma longa, Zea mays, Tabernaemontana divaricata, Eucalyptus globulus, Musa acuminata subsp. malaccensis, Solanum lycopersicum, Veronica longifolia, Malva sylvestris, Jatropha gossypiifolia, Sabina crenata, Anthocephalus chinensis, Citrus limon, Catharanthus roseus, Podocarpus spicatus, Tripterygium wilfordii, Spatholobus suberectus, Morinda umbellata, Juniperus squamata, Volvariella bombycina, Gypsophila perfoliate, Clausena anisum-olens,Ruscus aculeatus, Hypericum perforatum, Momordica charantia, Sphaeranthus amplexicaulis, Tridax procumbens, Trifolium pratense, Oryza sativa, Rosmarinus officinalis, Nelumbo nucifera, Crocus sativus, Citrus unshiu, Taxiphyllum taxirugum, Citrus sinensis, Ruscus aculeatus, Hypericum perforatum, or combinations thereof. In some embodiments, the plant extract includes a purified extract or a crude extract. In some embodiments, the extract can be directly derived from seeds. In some embodiments, the extract can be directly derived from whole seeds. In some embodiments, the extract can be directly derived from leaves. In some embodiments, the extract can be directly derived from fruit pulp. In some embodiments, the extract can be directly derived from tubers. In some embodiments, the extract can be directly derived from flowers. In some embodiments, the extract can be directly derived from roots. In some embodiments, the extract can be directly derived from roots. In some embodiments, the seeds, leaves, flowers, fruit pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30 °C to about 100 °C to remove oils prior to performing the extraction step.

[0021] In some embodiments, the plant extract includes Ruscus aculeatus. In some embodiments, the plant extract includes a purified extract or a crude extract of Ruscus aculeatus. In some embodiments, the extract can be directly derived from whole seeds. In some embodiments, the extract can be directly derived from leaves. In some embodiments, the extract can be directly derived from fruit pulp. In some embodiments, the extract can be directly derived from tubers. In some embodiments, the extract can be directly derived from flowers. In some embodiments, the extract can be directly derived from roots. In some embodiments, the extract can be directly derived from roots. In some embodiments, the seeds, leaves, flowers, fruit pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30 °C to about 100 °C to remove oils prior to performing the extraction step.

[0022] In some embodiments, the plant extract includes Phyllanthus emblica. In some embodiments, the plant extract includes a purified extract or a crude extract of Phyllanthus emblica. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before the extraction step is performed.

[0023] In some embodiments, the plant extract includes Malus domestica. In some embodiments, the plant extract includes a purified extract or a crude extract of Malus domestica. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before the extraction step is performed.

[0024] In some embodiments, the plant extract includes Tripterygium wilfordii. In some embodiments, the plant extract includes a purified extract or a crude extract of Tripterygium wilfordii. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before the extraction step is performed.

[0025] In some embodiments, the plant extract includes aloe vera. In some embodiments, the plant extract includes a purified extract or a crude extract of aloe vera. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flower, pulp, tuber, and / or root can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0026] In some embodiments, the plant extract includes cocoa. In some embodiments, the plant extract includes a purified extract or a crude extract of cocoa. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flower, pulp, tuber, and / or root can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0027] In some embodiments, the plant extract includes papaya. In some embodiments, the plant extract includes a purified extract or a crude extract of papaya. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flower, pulp, tuber, and / or root can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0028] In some embodiments, the plant extract includes Hypericum perforatum. In some embodiments, the plant extract includes a purified extract or a crude extract of Hypericum perforatum. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30 °C to about 100 °C to remove the oil before performing the extraction step.

[0029] In some embodiments, the plant extract includes Citrus unshiu. In some embodiments, the plant extract includes a purified extract or a crude extract of Citrus unshiu. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30 °C to about 100 °C to remove the oil before performing the extraction step.

[0030] In some embodiments, the plant extract includes Carica papaya. In some embodiments, the plant extract includes a purified extract or a crude extract of Carica papaya. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30 °C to about 100 °C to remove the oil before performing the extraction step.

[0031] In some embodiments, the plant extract includes lotus. In some embodiments, the plant extract includes a purified extract or a crude extract of lotus. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0032] In some embodiments, the plant extract includes elecampane. In some embodiments, the plant extract includes a purified extract or a crude extract of elecampane. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0033] In some embodiments, the plant extract includes Acacia luederitzii. In some embodiments, the plant extract includes a purified extract or a crude extract of Acacia luederitzii. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0034] In some embodiments, the plant extract includes Myrciaria dubia. In some embodiments, the plant extract includes a purified extract or a crude extract of Myrciaria dubia. In some embodiments, the extract can be directly sourced from whole seeds. In some embodiments, the extract can be directly sourced from leaves. In some embodiments, the extract can be directly sourced from pulp. In some embodiments, the extract can be directly sourced from tubers. In some embodiments, the extract can be directly sourced from flowers. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the seeds, leaves, flowers, pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove oils prior to performing the extraction step.

[0035] In some embodiments, the plant extract includes Myrciaria dubia. In some embodiments, the plant extract includes a purified extract or a crude extract of Myrciaria dubia. In some embodiments, the extract can be directly sourced from whole seeds. In some embodiments, the extract can be directly sourced from leaves. In some embodiments, the extract can be directly sourced from pulp. In some embodiments, the extract can be directly sourced from tubers. In some embodiments, the extract can be directly sourced from flowers. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the seeds, leaves, flowers, pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove oils prior to performing the extraction step.

[0036] In some embodiments, the plant extract includes Myrciaria dubia. In some embodiments, the plant extract includes a purified extract or a crude extract of Myrciaria dubia. In some embodiments, the extract can be directly sourced from whole seeds. In some embodiments, the extract can be directly sourced from leaves. In some embodiments, the extract can be directly sourced from pulp. In some embodiments, the extract can be directly sourced from tubers. In some embodiments, the extract can be directly sourced from flowers. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the seeds, leaves, flowers, pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove oils prior to performing the extraction step.

[0037] In some embodiments, the plant extract includes goldenrod. In some embodiments, the plant extract includes a purified extract or a crude extract of goldenrod. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0038] In some embodiments, the plant extract includes goldenrod. In some embodiments, the plant extract includes a purified extract or a crude extract of goldenrod. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0039] In some embodiments, the plant extract includes goldenrod. In some embodiments, the plant extract includes a purified extract or a crude extract of goldenrod. In some embodiments, the extract can be directly sourced from the whole seed. In some embodiments, the extract can be directly sourced from the leaves. In some embodiments, the extract can be directly sourced from the pulp. In some embodiments, the extract can be directly sourced from the tuber. In some embodiments, the extract can be directly sourced from the flower. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the extract can be directly sourced from the root. In some embodiments, the seed, leaves, flowers, pulp, tuber, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove the oil before performing the extraction step.

[0040] In some embodiments, the plant extract includes Chamaesyce macbridei. In some embodiments, the plant extract includes a purified extract or a crude extract of Chamaesyce macbridei. In some embodiments, the extract can be directly sourced from whole seeds. In some embodiments, the extract can be directly sourced from leaves. In some embodiments, the extract can be directly sourced from pulp. In some embodiments, the extract can be directly sourced from tubers. In some embodiments, the extract can be directly sourced from flowers. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the seeds, leaves, flowers, pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove oils prior to performing the extraction step.

[0041] In some embodiments, the plant extract includes Chamaesyce macbridei. In some embodiments, the plant extract includes a purified extract or a crude extract of Chamaesyce macbridei. In some embodiments, the extract can be directly sourced from whole seeds. In some embodiments, the extract can be directly sourced from leaves. In some embodiments, the extract can be directly sourced from pulp. In some embodiments, the extract can be directly sourced from tubers. In some embodiments, the extract can be directly sourced from flowers. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the seeds, leaves, flowers, pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove oils prior to performing the extraction step.

[0042] In some embodiments, the plant extract includes Chamaesyce macbridei. In some embodiments, the plant extract includes a purified extract or a crude extract of Chamaesyce macbridei. In some embodiments, the extract can be directly sourced from whole seeds. In some embodiments, the extract can be directly sourced from leaves. In some embodiments, the extract can be directly sourced from pulp. In some embodiments, the extract can be directly sourced from tubers. In some embodiments, the extract can be directly sourced from flowers. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the extract can be directly sourced from roots. In some embodiments, the seeds, leaves, flowers, pulp, tubers, and / or roots can be ground into a powder and then heated to a temperature selected from the range of about 30°C to about 100°C to remove oils prior to performing the extraction step.

[0043] In some embodiments, the oral composition comprises extracts from one or more plant sources. In some embodiments, the oral composition comprises extracts from two or more plant sources. In some embodiments, the oral composition comprises extracts from three or more plant sources.

[0044] In some embodiments, the extracts described herein include juices, infusions, and fermentation residues. These fermented plant source extracts or processed fraction products thereof can be used in consumable compositions, such as health-promoting compositions or tonics for humans and animals. As used herein, “plant source” refers to obtaining compounds from a plant, which can or can not refer to a pure extract of the plant.

[0045] In some embodiments, the compounds of the present disclosure are represented by a compound of Formula (I), or a salt thereof:

[0046]

[0047] (I).

[0048] In some embodiments, R 1 , R 2 , R 3 , and R 4 are each independently selected from hydrogen, deuterium, hydroxyl, halogen, ketone, optionally substituted ester, optionally substituted aryl, optionally substituted alkoxy, optionally substituted C1-C6-alkyl, optionally substituted -O-C1-C6-alkyl, or optionally substituted C3-C6-cycloalkyl. In some embodiments, R 1 , R 2 , and R 3 are each hydroxyl, R 4 is optionally substituted C1-C6-alkyl. In some embodiments, R 1 is hydrogen, R 2 , and R 3 are each hydroxyl, R 4 is optionally substituted -O-C1-C6-alkyl. In some embodiments, R 1 and R 4 are each hydrogen, R 2 , and R 3 are each hydroxyl. In some embodiments, R 1 is hydrogen, R 2 , R 3 , and R 4 are each ketone. In some embodiments, R 1 is hydrogen, R 2 , and R 3 are each hydroxyl, R 4 is ketone. In some embodiments, R 1 , R 2R is hydroxyl, R 3 R is hydroxyl, R 4 R is optionally substituted C1-C6-alkyl.

[0049] As used herein, "alkyl" refers to a straight-chain or branched hydrocarbon chain that contains only saturated (i.e., no double or triple bonds) carbon-carbon single bonds. Alkyl groups can have 1 to 20 carbon atoms (as do all number ranges recited herein, e.g., "1 to 20," each integer within the given range is recited; e.g., "1 to 20 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although the definition also contemplates the term "alkyl" without a specified number of carbon atoms). Alkyl groups can also be medium size alkyl groups having 1 to 10 carbon atoms. Alkyl groups can also be lower alkyl groups having 1 to 6 carbon atoms. Alkyl groups of a compound can be designated as "C1-C4 alkyl" or similar designations. By way of example only, "C1-C4" means that the alkyl chain has 1 to 4 carbon atoms, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, and hexyl. Alkyl groups can be substituted or unsubstituted.

[0050] As used herein, "aryl" refers to a carbocyclic (all-carbon) monocyclic or polycyclic aromatic ring system (including, for example, fused, bridged, or spiro ring systems in which two carbocyclic rings share a chemical bond, e.g., one or more aromatic rings with one or more aromatic or non-aromatic rings), which has a completely delocalized pi-electron system on at least one ring. The number of carbon atoms in an aryl group can vary. For example, aryl groups can be C6-C 14 R is optionally substituted C6-C 10 R is optionally substituted C6-C

[0051] As used herein, the term "halogen" or "halo" refers to any one of the radioactively stable atoms in column 7 of the Periodic Table, e.g., a chlorine (Cl), fluorine (F), bromine (Br), and iodine (I) group.

[0052] Whenever a group is described as being "optionally substituted" that group can be unsubstituted or substituted with one or more substituents as indicated. Likewise, when a group is described as being "unsubstituted or substituted" if substituted, the substituents can be selected from one or more substituents as indicated. If no substituents are indicated, it is meant that the indicated "optionally substituted" or "substituted" group can be substituted, individually and independently, with one or more groups selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxy, alkoxy, aryloxy, acyl, thiol, alkylthio, arylthio, cyano, halogen, thioxo, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfinyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, amino, monosubstituted amino, and disubstituted amino, as well as protected derivatives thereof.

[0053] In some embodiments, the compound of Formula (I) is a compound capable of use as a modulator of metabotropic glutamate receptors. In some embodiments, the modulator is capable of being an agonist of mGlu2. In some embodiments, the modulator is capable of being an agonist of mGlu3. In some embodiments, the modulator is capable of being an antagonist of mGlu2. In some embodiments, the modulator is capable of being an antagonist of mGlu3.

[0054] In some embodiments, the compound of Formula (I), the compounds of the present disclosure, and the plant extract include a compound selected from Table A:

[0055] Table A

[0056]

[0057]

[0058] In some aspects, provided herein is a composition comprising a compound of Table A and a carrier. As used herein, the term "carrier" refers to a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, talc, magnesium stearate, calcium stearate or zinc stearate, or stearic acid), or solvent enveloping material, involved in carrying or transporting the subject compound from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be compatible with the other ingredients of the formulation, and not harmful to the subject. Some examples of materials which can serve as carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate, and hydroxypropyl methyl cellulose; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laureate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) pH buffered solutions; (21) polyesters, polycarbonates and / or polyanhydrides; (22) fats, and / or phospholipids; and (23) other non-toxic compatible substances employed in conventional pharmaceutical preparations.

[0059] In some embodiments, the composition comprises a compound of Table A, which is a substantially pure compound. In some embodiments, the composition comprises less than about 5%, 4.5%, 4.0%, 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1.0%, 0.5%, 0.25%, 0.1% of impurities, or a range including and / or spanning the aforementioned values. As used herein, "substantially pure" refers to a state where one or more desired active compounds have been isolated and / or concentrated to a high degree, and where minimal amounts of unwanted impurities are present. In some embodiments, the compound is derived from a plant, and can be concentrated from the plant source without having to extract the compound from the plant in whole or in part. As a non-limiting example, a plant containing a compound of Table A can be processed to separate a particular portion of the plant that is rich in the compound of Table A from different portions of the plant that have a relatively lower concentration of the compound of Table A. As another non-limiting example, a plant containing a compound of Table A can be heated or pulverized so that any compound of Table A within the plant is more readily chemically extracted or broken down.

[0060] In some embodiments, the composition comprises about 0.1%, 0.25%, 0.50%, 0.75%, 1.0%, 1.5%, 2.5%, 5.0%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or a range of values including and / or spanning the aforementioned values, of the compounds of Table A. In some embodiments, the composition comprises about 10% to about 90% of the compounds of Table A. In some embodiments, the composition comprises about 20% to about 75% of the compounds of Table A. In some embodiments, the composition comprises about 25% to about 50% of the compounds of Table A. In some embodiments, the composition comprises about 15% of the compounds of Table A. In some embodiments, the composition comprises about 25% of the compounds of Table A. In some embodiments, the composition comprises about 50% of the compounds of Table A. In some embodiments, the composition comprises about 75% of the compounds of Table A. In some embodiments, the composition comprises about 90% of the compounds of Table A.

[0061] In some embodiments, the composition is formulated as an oral composition. In some embodiments, the composition comprises one or more of the compounds of Table A and a carrier. In some embodiments, the composition comprises Compound 1 and a carrier. In some embodiments, the composition comprises Compound 2 and a carrier. In some embodiments, the composition comprises Compound 3 and a carrier. In some embodiments, the composition comprises Compound 4 and a carrier. In some embodiments, the composition comprises Compound 5 and a carrier. In some embodiments, Compound 1 is an antagonist of mGlu2. In some embodiments, Compound 1 is an antagonist of mGlu3. In some embodiments, Compound 2 is an antagonist of mGlu2. In some embodiments, Compound 2 is an antagonist of mGlu3. In some embodiments, Compound 3 is an antagonist of mGlu2. In some embodiments, Compound 3 is an antagonist of mGlu3. In some embodiments, Compound 4 is an antagonist of mGlu2. In some embodiments, Compound 4 is an antagonist of mGlu3. In some embodiments, Compound 5 is an antagonist of mGlu2. In some embodiments, Compound 5 is an antagonist of mGlu3. In some embodiments, Compound 6 is an antagonist of mGlu2. In some embodiments, Compound 6 is an antagonist of mGlu3. In some embodiments, Compound 7 is an antagonist of mGlu2. In some embodiments, Compound 7 is an antagonist of mGlu3. In some embodiments, Compound 8 is an antagonist of mGlu2. In some embodiments, Compound 8 is an antagonist of mGlu3. In some embodiments, Compound 9 is an antagonist of mGlu2. In some embodiments, Compound 9 is an antagonist of mGlu3. In some embodiments, Compound 10 is an antagonist of mGlu2. In some embodiments, Compound 10 is an antagonist of mGlu3. In some embodiments, Compound 11 is an antagonist of mGlu2. In some embodiments, Compound 11 is an antagonist of mGlu3. In some embodiments, Compound 12 is an antagonist of mGlu2. In some embodiments, Compound 12 is an antagonist of mGlu3. In some embodiments, Compound 11 is an antagonist of mGlu3. In some embodiments, Compound 13 is an antagonist of mGlu2. In some embodiments, Compound 13 is an antagonist of mGlu3. In some embodiments, Compound 1 is an antagonist / negative allosteric modulator. In some embodiments, Compound 2 is an antagonist / negative allosteric modulator. In some embodiments, Compound 3 is an antagonist / negative allosteric modulator. In some embodiments, Compound 4 is an antagonist / negative allosteric modulator. In some embodiments, Compound 5 is an antagonist / negative allosteric modulator. In some embodiments, Compound 6 is an antagonist / negative allosteric modulator.In some embodiments, compound 7 is an antagonist / negative allosteric modulator. In some embodiments, compound 8 is an antagonist / negative allosteric modulator. In some embodiments, compound 9 is an antagonist / negative allosteric modulator. In some embodiments, compound 10 is an antagonist / negative allosteric modulator. In some embodiments, compound 11 is an antagonist / negative allosteric modulator. In some embodiments, compound 12 is an agonist / positive allosteric modulator. In some embodiments, compound 13 is an agonist / positive allosteric modulator.

[0062] In some embodiments, the oral composition includes a salt form of the compounds described herein. Salts of the compounds of the present disclosure refer to compounds that possess the desired pharmacological properties of the parent compound, including: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, ethane-1,2-diol, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, camphorsulfonic acid, 4-methylbenzenesulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound is replaced by a substituent such as alkyl groups, carbonyl groups, and the like.

[0063] In some embodiments, the oral composition includes a pharmaceutically acceptable salt form of a compound described herein. As used herein, the term "pharmaceutically acceptable salt" is a broad term, and, to an ordinary artisan, shall have its ordinary and customary meaning (and, to the exclusion of an special or customized meaning), and refers without limitation to a salt of a compound that does not cause significant irritation to an administered organism, and does not abrogate the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by reacting a compound with inorganic acids such as hydrohalic acid (e.g., hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid and phosphoric acid. Pharmaceutical salts can also be obtained by reacting a compound with an organic acid such as aliphatic, or aromatic carboxylic or sulfonic acids, for example formic, acetic, propionic, glycolic, pyruvic, malonic, maleic, fumaric, trifluoroacetic, benzoic, cinnamic, mandelic, succinic, lactic, malic, tartaric, citric, ascorbic, nicotinic, methanesulfonic, ethanesulfonic, p-toluenesulfonic, salicylic, stearic, muconic, butyric, phenylacetic, phenylbutyric, valeric, 1,2-ethanedisulfonic, 2-hydroxyethanesulfonic, benzenesulfonic, 2-naphthalenesulfonic or naphthalene- 2-sulfonic acid. Pharmaceutical salts can also be obtained by reacting a compound with a base to form a salt with an amine, such as ammonium salts (e.g., ammonium salts), alkali metal salts (e.g., lithium, sodium, or potassium salts), alkaline earth metal salts (e.g., calcium, magnesium, or aluminum salts), salts with organic amines (e.g., cyclohexylamine, dicyclohexylamine, tri (hydroxymethyl) aminomethane, C1-C7 alkyl amines, cyclohexylamine, dicyclohexylamine, triethanolamine, ethylenediamine, ethanolamine, diethanolamine, triethanolamine, tromethamine, and salts with amino acids such as arginine and lysine; or salts with inorganic bases (e.g., aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, and the like).

[0064] It is understood that in any compound described herein having one or more chiral centers, if no absolute stereochemistry is specified, each center can independently be of R-configuration, or S-configuration, or a mixture thereof. Thus, a compound provided herein can be enantiomerically pure, enantiomerically enriched, or can be a mixture of stereoisomers, and includes all diastereomeric and enantiomeric forms. Also, it is understood that in any compound described herein having one or more double bonds, which can give rise to geometric isomers, each double bond is independently a cis- or trans- isomer, or a mixture thereof. Stereochemically isomeric forms of the compounds described herein can be isolated by methods known to those of ordinary skill in the art, such as by separation of stereoisomeric forms using chiral column chromatography and the like. Likewise, it is intended that all tautomeric forms be included within the scope of the compounds described herein.

[0065] It is understood that the compounds described herein can be labeled with isotopes or by additional other means, including but not limited to the use of a chromophore or fluorescent moiety, bioluminescent label, or chemiluminescent label. Substitution with isotopes such as deuterium can afford certain therapeutic advantages due to greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements. Each chemical element as represented in a compound structure can comprise any isotope of said element. For example, in a compound structure, hydrogen atoms can be explicitly disclosed or understood to be present in the compound. At any position of the compound where hydrogen atoms can be present, the hydrogen atom can be any isotope of hydrogen including but not limited to hydrogen-1 (protium), hydrogen-2 (deuterium), hydrogen-3 (tritium). Thus, a compound as mentioned herein is intended to encompass all potential isotopic forms of the compound unless the context clearly dictates otherwise.

[0066] It is understood that the compounds described herein can be labeled with isotopes or by additional other means, including but not limited to the use of a chromophore or fluorescent moiety, bioluminescent label, or chemiluminescent label. Substitution with isotopes such as deuterium can afford certain therapeutic advantages due to greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements. Each chemical element as represented in a compound structure can comprise any isotope of said element. For example, in a compound structure, hydrogen atoms can be explicitly disclosed or understood to be present in the compound. At any position of the compound where hydrogen atoms can be present, the hydrogen atom can be any isotope of hydrogen including but not limited to hydrogen-1 (protium), hydrogen-2 (deuterium), hydrogen-3 (tritium). Thus, a compound as mentioned herein is intended to encompass all potential isotopic forms of the compound unless the context clearly dictates otherwise.

[0067] It is understood that the oral compositions, formulations, and methods described herein include the use of crystalline forms, amorphous phases, and / or pharmaceutically acceptable salts, solvates, hydrates, and conformational isomers of the compounds of some embodiments, as well as metabolites and active metabolites of these compounds having the same type of activity. A conformational isomer is a structure of a conformational isomer. Conformational isomerism is the phenomenon in molecules with the same structural formula, but different conformations (conformational isomers) of atoms around a rotating bond. In particular embodiments, the compounds described herein exist in solvated forms with pharmaceutically acceptable solvents (e.g., water, ethanol, and the like). In other embodiments, the compounds described herein exist in unsolvated forms. Solvates contain either stoichiometric or non-stoichiometric amounts of the solvent and can be formed during the process of crystallization with pharmaceutically acceptable solvents (e.g., water, ethanol, and the like). Hydrates are formed when the solvent is water. Alcohols are formed when the solvent is an alcohol. In addition, the compounds provided herein can exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. The compounds of some embodiments can be provided in other forms, including amorphous forms, milled forms, and nanoparticulate forms.

[0068] Likewise, it is understood that the compounds described herein, such as the compounds of some embodiments, include the compounds described herein in any form (e.g., pharmaceutically acceptable salts, prodrugs, crystalline forms, amorphous forms, solvated forms, enantiomeric forms, tautomeric forms, and the like).

[0069] In some embodiments, the composition can further comprise a preservative. In some embodiments, the amount of preservative can be about 0.01%, 0.05%, 0.1%, 0.15%, 0.20%, 0.25%, 0.50%, 0.75%, 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0% w / w, or a range including and / or spanning the aforementioned values. In some embodiments, the preservative can be, but is not limited to, selected from the group consisting of sodium benzoate, methyl paraben, propyl paraben, sodium nitrite, sulfur dioxide, sodium sorbate, and potassium sorbate. Other suitable preservatives include, but are not limited to, salts of ethylenediaminetetraacetic acid (also known as salts of ethylenediaminetetraacetic acid or EDTA, such as disodium EDTA).

[0070] In some embodiments, the composition can further comprise a sweetener. In some embodiments, the sweetener can be in an amount of about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or ranges including and / or spanning the aforementioned values. In some embodiments, the sweetener can comprise a natural sweetener. In some embodiments, the sweetener can comprise a synthetic sweetener. Non-limiting examples of sweeteners include sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, high fructose corn syrup, levulose, galactose, corn syrup solids, tagatose, polyols (e.g., sorbitol, mannitol, xylitol, lactitol, erythritol, and maltitol), hydrogenated starch hydrolysate, isomalt, trehalose, and mixtures thereof.

[0071] In some embodiments, the composition can further comprise a flavoring agent. In some embodiments, the flavoring agent can be in an amount of about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or ranges including and / or spanning the aforementioned values. In some embodiments, the flavoring agent can comprise a natural or artificial flavor. In specific embodiments, the flavoring agent comprises an essential oil, such as an oil derived from a plant or fruit, peppermint oil, spearmint oil, other mint oils, clove oil, cinnamon oil, wintergreen oil, bay oil, thyme oil, cedar leaf oil, mace oil, allspice oil, sage oil, nutmeg oil, and almond oil. In another specific embodiment, the flavoring agent comprises a plant extract or fruit essence, such as apple, banana, watermelon, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot, and mixtures thereof. In yet another specific embodiment, the flavoring agent comprises a citrus flavor, such as an extract, essence, or oil of lemon, lime, orange, tangerine, grapefruit, citron, or kumquat.

[0072] In some embodiments, the composition can further comprise a coloring agent. In some embodiments, the coloring agent can be in an amount of about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or ranges including and / or spanning the aforementioned values.

[0073] In some embodiments, the composition can further comprise at least one additive. In some embodiments, the amount of additive can be about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or comprise and / or span a range of the above values. In some embodiments, the at least one additive can be an emulsifier. In some embodiments, the additive can include one or more vitamins. In some embodiments, the additive can include one or more minerals. In some embodiments, the additive can include a stabilizer.

[0074] Formulations

[0075] Compositions comprising the plant extracts or compounds of the present disclosure can be combined with a carrier and provided in any suitable form for consumption by or administration to a subject. In this regard, the plant extracts or compounds are added as exogenous ingredients or additives to consumables. Suitable consumable forms include, but are not limited to, dietary supplements, food ingredients or additives, medical foods, nutraceuticals, or pharmaceutical compositions. In some embodiments, the plant extracts or compounds are provided in liquid or powder form.

[0076] “Food ingredient” or “food additive” as referred to herein includes an edible substance, whether or not it is to be consumed directly or indirectly as a component of or otherwise to affect the characteristics of any foodstuff (including any substance used in the production, manufacture, packaging, transport, or storage of a foodstuff). Food products, particularly functional food products, are foods that are fortified or enriched during processing to contain additional supplemental nutrients and / or beneficial ingredients. Food products according to the present disclosure can be, for example, in the form of butter, margarine, sweet or savory spreads, dressings, biscuits, health bars, breads, cakes, cereals, confectionery, desserts, soups, milk, yogurt or fermented milk products, cheese, fruit and vegetable drinks, fermented beverages, milkshakes, flavored water, tea, oil, or any other suitable food. In some embodiments, the food product is a whole food product, in which the concentration of the compound has been enriched by specific post-harvest and food production processing methods to levels that provide an effective amount of the compound.

[0077] A dietary supplement is an oral product containing a compound or extract of the disclosure intended to supplement the diet. A nutraceutical is a product derived from a food source that, in addition to the basic nutritional value in the food, provides additional health benefits. A pharmaceutical composition is defined as any component of a pharmaceutical product that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. Dietary supplements, nutraceuticals, and pharmaceutical compositions can exist in a variety of capsules, for example, in the form of tablets, coated tablets, pills, capsules, granules, pellets, soft capsules, caplets, liquids, powders, emulsions, suspensions, elixirs, syrups, and the like, as well as any other form suitable for use.

[0078] The pharmaceutical compositions disclosed herein can be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tableting processes. In addition, the amount of active ingredient contained in the pharmaceutical composition is such that it can be effective for its intended purpose. Many of the compounds used in the pharmaceutical compositions disclosed herein can be provided in the form of a salt having a pharmaceutically compatible counterion.

[0079] There are a variety of techniques for administering the compounds, salts, and / or compositions in the art, including, but not limited to, by oral, rectal, pulmonary, topical, aerosol, injection, infusion, and parenteral delivery, including by intramuscular, subcutaneous, intravenous, intramedullary injection, intrathecal, direct intraventricular, intraperitoneal, intranasal, and intraocular injection. In some embodiments, the compounds described herein (including a compound as described herein or a pharmaceutically acceptable salt thereof) can be administered orally.

[0080] The compounds, salts, and / or compositions can also be administered in a manner analogous to a local rather than a systemic administration, for example, by injection or implantation of the compound directly into the affected area, usually in the form of a depot or sustained release formulation. In addition, the compounds can also be administered by a targeted drug delivery system, for example, by liposomes coated with tissue-specific antibody. The liposomes will target the organ and be taken up selectively by the organ. For example, it can be desirable to target a respiratory disease or condition by intranasal or pulmonary delivery.

[0081] If desired, oral compositions can be presented in a pack or dispenser device, which can contain one or more unit dosage forms containing the active ingredient. The pack for example can include a metal or a plastic foil, such as a blister pack. The pack or dispenser device can be accompanied by instructions for administration. The pack or dispenser device can also be accommodated with a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drugs for human or veterinary administration. Such notice, for example, can be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or those matters presented in the approved product insert. Compositions comprising a compound and / or salt described herein formulated in a compatible pharmaceutical carrier can also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.

[0082] A compound, salt, and / or pharmaceutical composition can be provided to a treating physician or other medical care professional in the form of a kit. A kit is a package containing a container that includes a compound in a suitable pharmaceutical composition, and instructions for administering the pharmaceutical composition to a subject. The kit can optionally include one or more additional therapeutic agents. The kit can also include separate doses of the compound or pharmaceutical composition for consecutive or sequential administration. The kit can optionally include one or more diagnostic tools and instructions for use. The kit can include a suitable delivery device, such as a syringe, and instructions for administering the compound and any other therapeutic agents. The kit can optionally include instructions regarding storage, reconstitution (if applicable), and administration of any or all of the therapeutic agents contained. The kit can include multiple containers to reflect the number of administrations to be given to the subject.

[0083] In some embodiments, the oral composition described herein may be administered at a dose ranging from about 0.1 to 200 mg per kilogram of body weight. In some embodiments, the oral composition described herein may be administered at doses ranging from about 0.1 to 1 mg, 0.5 to 1 mg, 0.1 to 10 mg, 0.5 to 10 mg, 1 to 10 mg, 1 to 20 mg, 1 to 30 mg, 1 to 40 mg, 1 to 50 mg, 1 to 60 mg, 1 to 70 mg, 1 to 80 mg, 1 to 90 mg, 1 to 100 mg, 1 to 200 mg, 1 to 300 mg, 1 to 400 mg, 1 to 500 mg, 1 to 600 mg, 1 to 700 mg, 1 to 800 mg, 1 to 900 mg, 1 to 1000 mg, 1 to 11 mg, 1 to 12 mg, 1 to 13 mg, 1 to 13 mg, 1 to 14 mg per kilogram of body weight. g, 1-15mg, 1-16mg, 1-17mg, 1-18mg, 1-19mg, 10-20mg, 10-30mg, 10-40mg, 10-50mg, 10-60mg, 10-70mg, 10-80mg, 10-90mg, 10-100mg, 10-200mg, 10-300mg, 10-400mg, 10-500mg, 10-600mg, 10-700mg, 10-800mg, 10-900mg, 10-1000mg, 20-30mg, 20-40mg, 20-50mg, 20-60mg, 20-70mg, 20-80m g, 20-90mg, 20-100mg, 20-200mg, 20-300mg, 20-400mg, 20-500mg, 20-600mg, 20-700mg, 20-800mg, 20-900mg, 20-1000mg, 30-40mg, 30-50mg, 3 0-60mg, 30-70mg, 30-80mg, 30-90mg, 30-100mg, 30-200mg, 30-300mg, 30-400mg, 30-500mg, 30-600mg, 30-700mg, 30-800mg, 30-900mg, 30-1000 mg, 40-50mg, 40-60mg, 40-70mg, 40-80mg, 40-90mg, 40-100mg, 40-200mg, 40-300mg, 40-400mg, 40-500mg, 40-600mg, 40-700mg, 40-800mg, 40-9 00mg, 40-1000mg, 50-60mg, 50-70mg, 50-80mg, 50-90mg, 50-100mg, 50-200mg, 50-300mg, 50-400mg, 50-500mg, 50-600mg, 50-700mg, 50-800mg,50-900mg, 60-70mg, 60-80mg, 60-90mg, 60-100mg, 60-200mg, 60-300mg, 60-400 mg, 60-500mg, 60-600mg, 60-700mg, 60-800mg, 60-900mg, 60-1000mg, 70-80mg, 70-90mg, 70-100mg, 70-200mg, 70-300mg, 70-400mg, 70-500mg, 70-600mg, 70-7 00mg, 70-800mg, 70-900mg, 70-1000mg, 80-90mg, 80-100mg, 80-200mg, 80-300m Dosage ranges from g, 80-400mg, 80-500mg, 80-600mg, 80-700mg, 80-800mg, 80-900mg, 80-100mg, 90-100mg, 90-200mg, 90-300mg, 90-400mg, 90-500mg, 90-600mg, 90-700mg, 90-800mg, 90-900mg, 90-1000mg, 100-150mg, 100-200mg, 100-300mg, 100-400mg, 100-500mg, 100-600mg, 100-700mg, 100-800mg, 100-900mg, or 100-1000mg. In some embodiments, the oral compositions described herein are administered at doses of approximately 0.01 mg, 0.02 mg, 0.03 mg, 0.05 mg, 0.07 mg, 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, 10 mg, 10.5 mg, 11 mg, 11.5 mg, 12 mg, 12.5 mg, 13 mg, 13.5 mg, 14 mg, and 14.5 mg per kilogram of body weight. mg, 15mg, 15.5mg, 16mg, 16.5mg, 17mg, 17.5mg, 18mg, 18.5mg, 19mg, 19.5mg, 20mg, 20.5mg, 21mg, 21.5mg, 22mg, 22.5mg, 23mg, 23.5mg, 24mg, 2 4.5mg, 25mg, 25.5mg, 26mg, 26.5mg, 27mg, 27.5mg, 28mg, 28.5mg, 29mg, 29.5mg, 30mg, 30.5mg, 31mg, 32mg, 33mg, 34mg, 35mg, 36mg, 37mg, 38mg,39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 80 mg, 90 mg, or 95 mg. In some embodiments, the oral compositions described herein are administered at a dose of less than about 0.01 mg, 0.02 mg, 0.03 mg, 0.05 mg, 0.07 mg, 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, 10 mg, 10.5 mg, 11 mg, 11.5 mg, 12 mg, 12.5 mg, 13 mg, 13.5 mg, 14 mg, 14.5 mg, 15 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28 mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg per square meter of body surface area. In some embodiments, the oral compositions described herein are administered at a dose of greater than about 0.01 mg, 0.02 mg, 0.03 mg, 0.05 mg, 0.07 mg, 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, 10 mg, 10.5 mg, 11 mg, 11.5 mg, 12 mg, 12.5 mg, 13 mg, 13.5 mg, 14 mg, 14.5 mg, 15 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28 mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg per kilogram of subject body mass.29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, or 100 mg of the dose is administered.

[0084] mg-100 mg, 2 mg-10 mg, 2 mg-25 mg, 2 mg-30 mg, 2 mg-50 mg, 2 mg-75 mg, 2 mg-100 mg, 3 mg-10 mg, 3 mg-25 mg, 3 mg-30 mg, 3 mg-50 mg, 3 mg-75 mg, 3 mg-100 mg, 4 mg-100 mg, 5 mg-10 mg, 5 mg-25 mg, 5 mg-30 mg, 5 mg-50 mg, 5 mg-75 mg, 5 mg-300 mg, 5 mg-200 mg, 7.5 mg-15 mg, 7.5 mg-25 mg, 7.5 mg-30 mg, 7.5 mg-50 mg, 7.5 mg-75 mg, 7.5 mg-100 mg, 7.5 mg-200 mg, 10 mg-20 mg, 10 mg-25 mg, 10 mg-50 mg, 10 mg-75 mg, 10 mg-100 mg, 15 mg-30 mg, 15 mg-50 mg, 15 mg-100 mg, 20 mg-20 mg, 20 mg-100 mg, 30 mg-100 mg, 40 mg-100 mg, 10 mg-80 mg, 15 mg-80 mg, 20 mg-80 mg, 30 mg-80 mg, 40 mg-80 mg, 10 mg-60 mg, 15 mg-60 mg, 20 mg-60 mg, 30 mg-60 mg, or about 40 mg-60 mg. In some embodiments, the oral composition described herein is administered in an amount of about 1 mg-5 mg, 1 mg-7.5 mg, 2.5 mg-5 mg, 2.5 mg-7.5 mg, 5 mg-7.5 mg, 5 mg-9 mg, 5 mg-10 mg, 5 mg-12 mg, 5 mg-14 mg, 5 mg-15 mg, 5 mg-16 mg, 5 mg-18 mg, 5 mg-20 mg, 5 mg-22 mg, 5 mg-24 mg, 5 mg-26 mg, 5 mg-28 mg, 5 mg-30 mg, 5 mg-32 mg, 5 mg-34 mg, 5 mg-36 mg, 5 mg-38 mg, 5 mg-40 mg, 5 mg-42 mg, 5 mg-44 mg, 5 mg-46 mg, 5 mg-48 mg, 5 mg-50 mg, 5 mg-52 mg,5mg-54mg, 5mg-56mg, 5mg-58mg, 5mg-60mg, 7mg-7.7mg, 7mg-9mg, 7mg-10mg, 7mg-12mg, 7mg-14mg, 7mg-15mg, 7mg-16mg, 7mg-18mg, 7mg-20mg, 7mg-22mg, 7mg-24mg, 7mg-26mg, 7mg-28mg, 7mg-30mg, 7mg-32mg, 7mg-34mg, 7mg-36mg, 7mg-38mg, 7mg-40mg, 7mg-42mg, 7mg-44mg, 7mg-46mg, 7mg-48mg, 7mg-50mg, 7mg-52mg, 7mg-54mg, 7mg-56mg, 7mg-58mg, 7mg-60mg, 9mg-10mg, 9mg-12mg, 9mg-14mg, 9mg-15mg, 9mg-16mg, 9mg-18mg, 9mg-20mg, 9mg-22mg, 9mg-24mg, 9mg-26mg, 9mg-28mg, 9mg-30mg, 9mg-32mg, 9mg-34mg, 9mg-36mg, 9mg-38mg, 9mg-40mg, 9mg-42mg, 9mg-44mg, 9mg-46mg, 9mg-48mg, 9mg-50mg, 9mg-52mg, 9mg-54mg, 9mg-56mg, 9mg-58mg, 9mg-60mg, 10mg-12mg, 10mg-14mg, 10mg-15mg, 10mg-16mg, 10mg-18mg, 10mg-20mg, 10mg-22mg, 10mg-24mg, 10mg-26mg, 10mg-28mg, 10mg-30mg, 10mg-32mg, 10mg-34mg, 10mg-36mg, 10mg-38mg, 10mg-40mg, 10mg-42mg, 10mg-44mg, 10mg-46mg, 10mg-48mg, 10mg-50mg, 10mg-52mg, 10mg-54mg, 10mg-56mg, 10mg-58mg, 10mg-60mg, 12mg-14mg, 12mg-15mg, 12mg-16mg, 12mg-18mg, 12mg-20mg, 12mg-22mg, 12mg-24mg, 12mg-26mg, 12mg-28mg, 12mg-30mg, 12mg-32mg, 12mg-34mg, 12mg-36mg, 12mg-38mg, 12mg-40mg, 12mg-42mg, 12mg-44mg, 12mg-46mg, 12mg-48mg, 12mg-50mg,12mg-52mg, 12mg-54mg, 12mg-56mg, 12mg-58mg, 12mg-60mg, 15mg-16mg, 15mg-18mg, 15mg-20mg, 15mg-22mg, 15mg-24mg, 15mg-26mg, 15mg-28mg, 15mg-30mg, 15mg-32mg, 15mg-34mg, 15mg-36mg, 15mg-38mg, 15mg-40mg, 15mg-42mg, 15mg-44mg, 15mg-46mg, 15mg-48mg, 15mg-50mg, 15mg-52mg, 15mg-54mg, 15mg-56mg, 15mg-58mg, 15mg-60mg, 17mg-18mg, 17mg-20mg, 17mg-22mg, 17mg-24mg, 17mg-26mg, 17mg-28mg, 17mg-30mg, 17mg-32mg, 17mg-34mg, 17mg-36mg, 17mg-38mg, 17mg-40mg, 17mg-42mg, 17mg-44mg, 17mg-46mg, 17mg-48mg, 17mg-50mg, 17mg-52mg, 17mg-54mg, 17mg-56mg, 17mg-58mg, 17mg-60mg, 20mg-22mg, 20mg-24mg, 20mg-26mg, 20mg-28mg, 20mg-30mg, 20mg-32mg, 20mg-34mg, 20mg-36mg, 20mg-38mg, 20mg-40mg, 20mg-42mg, 20mg-44mg, 20mg-46mg, 20mg-48mg, 20mg-50mg, 20mg-52mg, 20mg-54mg, 20mg-56mg, 20mg-58mg, 20mg-60mg, 22mg-24mg, 22mg-26mg, 22mg-28mg, 22mg-30mg, 22mg-32mg, 22mg-34mg, 22mg-36mg, 22mg-38mg, 22mg-40mg, 22mg-42mg, 22mg-44mg, 22mg-46mg, 22mg-48mg, 22mg-50mg, 22mg-52mg, 22mg-54mg, 22mg-56mg, 22mg-58mg, 22mg-60mg, 25mg-26mg, 25mg-28mg, 25mg-30mg, 25mg-32mg, 25mg-34mg, 25mg-36mg, 25mg-38mg, 25mg-40mg, 25mg-42mg, 25mg-44mg, 25mg-46mg,25-48, 25-50, 25-52, 25-54, 25-56, 25-58, 25-60, 27-28, 27-30, 27-32, 27-34, 27-36, 27-38, 27-40, 27-42, 27-44, 27-46, 27-48, 27-50, 27-52, 27-54, 27-56, 27-58, 27-60, 30-32, 30-34, 30-36, 30-38, 30-40, 30-42, 30-44, 30-46, 30-48, 30-50, 30-52, 30-54, 30-56, 30-58, 30-60, 33-34, 33-36, 33-38, 33-40, 33-42, 33-44, 33-46, 33-48, 33-50, 33-52, 33-54, 33-56, 33-58, 33-60, 36-38, 36-40, 36-42, 36-44, 36-46, 36-48, 36-50, 36-52, 36-54, 36-56, 36-58, 36-60, 40-42, 40-44, 40-46, 40-48, 40-50, 40-52, 40-54, 40-56, 40-58, 40-60, 43-46, 43-48, 43-50, 43-52, 43-54, 43-56, 43-58, 42-60, 45-48, 45-50, 45-52, 45-54, 45-56, 45-58, 45-60, 48-50, 48-52, 48-54, 48-56, 48-58, 48-60, 50-52, 50-54, 50-56, 50-58, 52-54, 52-56, 52-58, 52-60, 54-56, 54-58, 54-60, 56-58, 56-60, 58-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-60, 60-6050 mg-60 mg, 52 mg-54 mg, 52 mg-56 mg, 52 mg-58 mg, or 52 mg-60 mg. In some embodiments, the oral composition described herein has a dose greater than, equal to, or about 0.1 mg, 0.3 mg, 0.5 mg, 0.75 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 5 mg, about 10 mg, about 12.5 mg, about 13.5 mg, about 15 mg, about 17.5 mg, about 20 mg, about 22.5 mg, about 25 mg, about 27 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, or about 1000 mg. In some embodiments, the oral composition described herein has a dose about less than about 0.5 mg, 0.75 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 5 mg, about 10 mg, about 12.5 mg, about 13.5 mg, about 15 mg, about 17.5 mg, about 20 mg, about 22.5 mg, about 25 mg, about 27 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 125 mg, about 150 mg, or about 200 mg.

[0085] For preparing solid compositions such as tablets or capsules, the compound or extract is mixed with a carrier (e.g., conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate or gums) and other diluents (e.g., water) to form a solid composition. The solid composition is then subdivided into unit dosage forms containing effective amounts of the compounds of the present disclosure. The tablets or pills of the compound or extract can be coated or otherwise compounded to provide a dosage form with a prolonged action advantage.

[0086] Liquid forms in which a compound or extract of the disclosure can be employed for oral or parenteral administration include aqueous solutions, suitably flavoured syrups, aqueous or oil suspensions, flavoured emulsions with edible oils, and colas, and like vehicles. Disintegrating or suspending agents for aqueous suspensions include synthetic natural gums, such as tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone or gelatin. Liquid preparations for oral administration can be in the form of solutions, syrups or suspensions, or can be dry products for reconstitution with water or other suitable vehicle at the time of administration. Such liquid preparations can be prepared using conventional methods and can contain acceptable additives such as suspending agents (e.g. sorbitol syrup, methyl cellulose, or hydrogenated food fat); emulsifying agents (e.g. lecithin or acacia); non- aqueous vehicles (e.g. almond oil, oily esters, or ethyl alcohol); preservatives (e.g. methyl or propyl p-hydroxybenzoate or sorbic acid); and artificial or natural colouring and / or flavouring agents.

[0087] The process of preparing a formulation or composition of the disclosure includes the step of bringing a compound or extract of the disclosure into association with a carrier and, optionally, one or more accessory ingredients and / or active ingredients. In general, the preparations of the disclosure are prepared by uniformly and intimately bringing a compound or extract of the disclosure into association with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product. Thus, a formulation of the disclosure can comprise a compound or extract described herein in combination with a suitable carrier, or a major proportion of such a carrier.

[0088] When a compound or extract of the disclosure is administered as pharmaceutical, nutraceutical or dietary supplement to humans and animals, it can be used alone, or as a composition, for example, containing from 0.1% to 99% of the active ingredient in combination with an acceptable carrier. In some embodiments, a compound or extract of the disclosure can be administered at about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99% w / w or a range including and / or spanning the aforementioned values.

[0089] Food products, particularly functional foods, are foods that are fortified or enriched during processing to contain additional supplemental nutrients and / or beneficial ingredients. Food products according to the present disclosure can be, for example, in the form of butter, margarine, sweet or savory spreads, dressings, cookies, health bars, breads, cakes, cereals, candies, confections, soups, milk, yogurt or fermented dairy products, cheese, juice and vegetable drinks, fermented beverages, milkshakes, flavored water, tea, oil, or any other suitable food. In some embodiments, the food product is a whole food product, in which the concentration of the compound has been enriched by specific post-harvest and food production processing methods to levels that provide an effective amount of the compound. In some embodiments, the food product includes one or more compounds described herein and a source of fiber. In some embodiments, the food product includes one or more compounds described herein. In some embodiments, the food product is a food bar. In some embodiments, the food bar comprises about 0.01% to about 20% (w / w) of one or more compounds described herein. In some embodiments, the food bar comprises about 0.1% to about 10% (w / w) of one or more compounds described herein. In some embodiments, the food product is a chip. In some embodiments, the food chip comprises about 0.01% to about 20% (w / w) of one or more compounds described herein. In some embodiments, the food chip comprises about 0.1% to about 10% (w / w) of one or more compounds described herein.

[0090] The compounds, compositions, and extracts of the present disclosure can be prepared as nutritional formulations, such as foods, including medical foods or functional foods. A “medical food or functional food” is defined as a food that is consumed as part of a diet and that has been demonstrated to have a physiological benefit and / or to reduce the risk of developing a disease or condition, such as a chronic disease, beyond basic nutritional function. By way of example, but not limitation, medical foods and functional foods can include one or more of the following ingredients: a compound described herein, a composition described herein, an extract described herein, a vitamin, a mineral, an herbal, a botanical, an amino acid, a dietary substance intended for ingestion to supplement the diet by increasing total dietary intake, a concentrate, metabolite, constituent, extract, or combination of any of these. Dietary supplements can also be added to foods, such as functional foods designed to promote health or prevent disease or disorder. If administered as a pharmaceutical formulation, the composition can be administered to a patient as a prophylactic or therapeutic in any of a variety of ways. In some embodiments, the compositions described herein can be administered alone or in combination with other additives or agents, and can be combined with a physiologically acceptable carrier. The effective amount and method of administration of a particular formulation, as well as the goal, can vary depending on the individual subject, the stage of the disease or condition, and other factors apparent to those skilled in the art. For both pharmaceutical formulations and nutritional formulations, the concentration of the composition can be monitored (e.g., plasma levels can be monitored) over the course of treatment to ensure that the desired levels are maintained.

[0091] In some embodiments, the food product includes a carbohydrate. A variety of carbohydrates are used in food products, such as various sugars and starches. Carbohydrates are an important energy source for the human body, including complex carbohydrates (such as whole grains and vegetables) and simple carbohydrates (such as sugars and refined grains). Several common carbohydrates used in food products include: starches, sugars, fructose, maltodextrin, dextrose, corn syrup, oligosaccharides, cellulose, complex carbohydrates such as inulin which can be added to processed foods as prebiotic fiber. The concentration of the carbohydrate can vary depending on the intended use of the product, according to the present disclosure. In some embodiments, the carbohydrate can comprise from about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the carbohydrate can comprise from about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the food product can comprise a carbohydrate in a range having a high value to a low value, the high and low values being independently selected from about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range including, between, and / or spanning the aforementioned values.

[0092] In some embodiments, the food product can include sugar. Sugars, such as high fructose corn syrup, sucrose, glucose syrup, preferred sugar, and other sweeteners are often added to processed foods to make them more palatable. Additionally, sugar alcohols or maltodextrins can also be added to food products to reduce caloric content and / or enhance the nutritional profile of the product. In some embodiments, the food product can include one or more sugars that are slowly or incompletely digested by the human body, even if not completely. These sugars can include isomaltulose, panose, and branched oligomers with a degree of polymerization of four or higher. Other non-limiting examples of sugars include sucrose, HFCS, fructose, brown sugar (which can be partially or fully refined), powdered sugar (also known as confectioner’s sugar), high fructose corn syrup, honey, molasses, maple syrup, agave nectar, coconut sugar, date sugar, concentrated fruit juice, maltodextrin, dextrose, glucose syrup, maple syrup, molasses, and lactose. The concentration of sugar can vary depending on the intended use of the product, according to the present disclosure. In some embodiments, the sugar can comprise from about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the sugar component comprises from about 2 wt.% to about 10 wt.% of the composition. In some embodiments, a plurality of sugars can comprise from about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the food product can include sugars in a high value and a low value, the high value and the low value being independently selected from about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range including, between, and / or spanning the aforementioned values.

[0093] In some embodiments, the food product includes a fiber source. In some embodiments, the food product includes from about 5% to about 30% (w / w) fiber. In some embodiments, the food product includes at least 10% fiber. In some embodiments, the food product includes at least 15% fiber. In some embodiments, the food product includes at least 20% fiber. In some embodiments, the food product includes at least 30% fiber. In some embodiments, the fiber can be selected from psyllium husks, inulin, beta-glucan, acacia fiber, pectin, wheat dextrin, cellulose, fructooligosaccharides, guar gum, fruit fiber, or combinations thereof. In some embodiments, the fiber is a soluble dietary fiber.

[0094] In some embodiments, the food product can include protein. Depending on the product, the concentration of protein included can be within a range. Protein sources can include soy protein, soy flour, soy protein isolate, whey protein isolate, casein, gelatin, pulse protein isolate, soy protein concentrate, egg albumin or egg white, wheat protein concentrate, pulse protein concentrate, and mixtures thereof. In some embodiments, a meat product such as a beef jerky, sausage, or meatball can include protein as a major ingredient. The concentration of protein included can be about 10% to about 25% of the total ingredients. In dairy products such as cheese, yogurt, or milk, protein such as casein or whey can be a major ingredient. The concentration of protein included can be about 3% to about 15% of the total ingredients. In plant-based products such as tofu, tempeh, or seitan, protein from soy, pea, pulse, or wheat can be a major ingredient. The concentration of protein included can be about 10% to about 25% of the total ingredients. In energy and protein bars, protein such as whey or soy, or any protein according to the present disclosure can be added to provide a protein source. The concentration of protein included can be about 10% to about 25% of the total ingredients. According to the present disclosure, the concentration of protein can vary depending on the intended use of the product. In some embodiments, the protein can comprise about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the protein can comprise about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the food product can include protein in a high value and a low value, independently selected from about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range including, between, and / or spanning the aforementioned values.

[0095] In some embodiments, the food product can include starch. In some embodiments, the food product can additionally include a starch ingredient in an amount sufficient to provide about 5% to 45%, or about 10% to 30%, or about 15% to 25% starch in the food product. The starch component can include not only pure added grain flour or other particulates, but also any starch fraction provided by other ingredients such as oat bran or soy protein. In some embodiments, the starch can include any conventionally used starch or grain flour ingredient for ready-to-eat cereals. Exemplary suitable starchy grains include grain flours from major grains including wheat, rice, corn (maize), oat, barley, rye, or starch fractions isolated from grain flowers including, for example, corn starch, wheat starch, rice starch, and various processed starches including pregelatinized starch and / or modified starches.

[0096] In some embodiments, the food product can include flour. Several types of flour can be used in accordance with the present disclosure. For example, common flour types used in food include all-purpose flour (which, like most other flours, can contain a protein component), whole wheat flour, bread flour, cake flour, pastry flour, self-rising flour, and gluten-free flour. The concentration of flour can vary depending on the intended use of the product in accordance with the present disclosure. For example, in baked products such as bread, cakes, and cookies, flour is typically a major ingredient and can be included at a concentration of 50% to 100% of the total dry ingredients. In soups and sauces, flour is typically used as a thickener and can be included at a concentration of 1% to 5% of the total ingredients. In batters and breading: In fried foods such as chicken or fish, flour is typically used as part of the batter or breading and can be included at a concentration of 20% to 50% of the total dry ingredients. In snack foods such as cookies and potato chips, flour can be included at a concentration of 30% to 70% of the total ingredients. In some embodiments, flour can comprise about 1 wt.% to about 95 wt.% of the food product. In some embodiments, flour can comprise about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the food product can include flour in a high value and a low value independently selected from about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range including, between, and / or spanning the aforementioned values.

[0097] In some embodiments, the food product can include fat. In some embodiments, the food product can include oil. In some embodiments, the food product can include one or more fats or oils. Several types of fats can be used in accordance with the present disclosure. For example, common fat types include butter, margarine, vegetable oil, shortening, and lard. The concentration of fat can vary depending on the intended use of the product in accordance with the present disclosure. In baked products such as cakes, cookies, and pastries, fats such as butter, shortening, or oil are often used to provide moisture, flavor, and texture. In some embodiments, the concentration of fat included can be 10% to 30% of the total ingredients. In some embodiments, such as in sauces and dressings, fats such as olive oil or mayonnaise are often used to provide flavor and texture. In some embodiments, the concentration of fat included can be 10% to 30% of the total ingredients. In fried foods such as chicken or French fries, fats such as vegetable oil or lard are used for frying, and the concentration included can be 30% to 60% of the total ingredients. In snack foods such as potato chips and cookies, fats such as vegetable oil or palm oil are often used to provide flavor and texture. In some embodiments, the concentration of fat included can be 10% to 30% of the total ingredients. In some embodiments, the fat can comprise about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the fat can comprise about 1 wt.% to about 95 wt.% of the food product. In some embodiments, the food product can include fat in a high value and a low value, the high value and the low value being independently selected from about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range including, between, and / or spanning the aforementioned values.

[0098] In some embodiments, the food product can include one or more additional ingredients. If desired, the disclosed food products can also include a variety of materials designed to improve their aesthetic or nutritional qualities. These adjunct materials can include vitamin and / or mineral fortifiers, colors, flavors, sweeteners, and mixtures thereof. The precise ingredient concentrations can vary somewhat. Generally, however, such materials can each comprise about 0.01% to about 5%, or about 0.1% to 2%, by weight of the food product, on a dry weight basis. One particularly useful material is common salt. In some embodiments, salt comprises about 0.1% to 5%, or about 0.5% to 4.0%, of the food product.

[0099] In some embodiments, the food product is derived from a plant. In some embodiments, the food product is derived from a cannabis hull. In some embodiments, the food product is a solid food. In some embodiments, the food product is a semi-solid food. In some embodiments, the food product is an extruded product, a baked product, a pressed cake, a prepared food, a food bar, a cereal, a chip, or a spread.

[0100] A dietary supplement is an oral product that contains a compound or extract of the disclosure, intended to supplement the diet. A nutraceutical is a product derived from a food source that, in addition to the basic nutritional value in the food, provides additional health benefits. A pharmaceutical composition is defined as any component of a pharmaceutical product intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. Dietary supplements, nutraceuticals, and pharmaceutical compositions can exist in a variety of capsules, in forms such as tablets, coated tablets, pills, capsules, granules, pellets, soft capsules, caplets, liquids, powders, emulsions, suspensions, elixirs, syrups, and the like, as well as any other suitable form for use. In some embodiments, the compositions described herein are provided as a dietary supplement. In some embodiments, the dietary supplement is provided in a capsule, tablet, powder, or liquid form. In some embodiments, the compositions described herein are provided as a nutritional supplement. In some embodiments, the nutritional supplement is provided in a capsule, tablet, powder, or liquid form. In some embodiments, the compositions described herein are provided as a pharmaceutical. In some embodiments, the pharmaceutical is provided in a capsule, tablet, powder, or liquid form.

[0101] A compound, salt, and / or pharmaceutical composition can be provided to an attending physician or other health care professional in the form of a kit. A kit is a package containing a container that contains a compound in a suitable pharmaceutical composition, along with instructions for administering the pharmaceutical composition to a subject. The kit can optionally also contain one or more additional therapeutic agents. The kit can also contain separate doses of the compound or pharmaceutical composition for consecutive or sequential administration. The kit can optionally contain one or more diagnostic tools and instructions for use. The kit can contain suitable delivery devices, such as syringes and the like, along with instructions for administering the compound and any other therapeutic agents. The kit can optionally contain instructions regarding storage, reconstitution (if applicable), and administration of any or all of the therapeutic agents contained. The kit can contain multiple containers to reflect the number of administrations to be given to the subject.

[0102] Methods and uses

[0103] The disclosure provides methods and uses for treating, preventing, alleviating, modulating, or mitigating stress, a symptom of stress, or the deleterious effects of chronic stress in a subject. According to these methods, an effective amount of a compound or composition of the disclosure is provided to a subject in need thereof, so as to treat, alleviate, ameliorate, restore, modulate, or mitigate stress in the subject. As used herein, the term “subject” refers to an animal, preferably a mammal. In some embodiments, the subject is a veterinary, companion, farm, laboratory, or zoological animal. In other embodiments, the subject is a human.

[0104] In some embodiments, the methods and uses for treating, preventing, reducing, modulating, or ameliorating stress disorders in a subject can include administering a therapeutically effective amount of a compound or composition described herein. In some embodiments, administering a therapeutically effective amount of a compound includes orally administering the compound. Orally administering the compound can include ingesting a natural product in which the compound is a naturally occurring constituent, an enriched natural product, and a composition that is substantially pure according to the compounds of the present disclosure. As used herein, the terms “stress” or “stress disorder” encompass psychological and physical diseases and conditions as recognized and understood by medical practitioners in the relevant medical fields. Stress and / or stress disorders can manifest in a variety of symptoms, including but not limited to sleep disturbances and anxiety. Stress disorders encompass a range of mental health conditions that can be caused by experiencing or witnessing a traumatic event. Examples of such disorders include, but are not limited to, post-traumatic stress disorder (PTSD), a condition that can occur after a person experiences a severe trauma, such as combat, a natural disaster, a serious accident, or a violent personal assault. Acute stress disorder (ASD) is another example, which shares similar symptoms to PTSD but occurs immediately after a traumatic event and typically resolves within a month. Adjustment disorder is also relevant, which is characterized by an inability to adapt or cope with a specific stressor, such as a major life change, resulting in noticeable emotional or behavioral symptoms. These disorders manifest differently in different individuals, showing the complex effects of stress on mental health.

[0105] As used herein, the terms “treating,” “treatment,” “treat,” and the like refer to affecting a subject, tissue, or cell to obtain a desired pharmacological and / or physiologic effect. The effect can be prophylactic in terms of completely or partially preventing a disease or symptom associated with the disease, or it can be therapeutic in terms of a partial or complete cure for a disease or adverse effect attributed to the disease. Thus, reference to “treating” a stress disorder encompasses: (a) helping a subject to reduce stress; (b) helping a subject to maintain a lower level of stress; (c) reducing or alleviating the effects of a stress disorder, such as enhancing normalcy; or (d) preventing a subject who is predisposed or at risk of developing a stress disorder from developing the stress disorder, such that the stress disorder does not develop or occur in the subject, or develops in a less severe form.

[0106] “Effective amount” refers to an amount of a drug that, when administered to a patient, provides a sufficient amount to achieve an effect. In the case of a method of treatment, the effect can be treating a stress disorder. Thus, an “effective amount” can be a “therapeutically effective amount.” A “therapeutically effective amount” refers to an amount of a drug that, when administered to a subject, provides a sufficient amount to treat a disease or symptoms of a disease.

[0107] In some embodiments, the present disclosure provides methods of treating, preventing, managing, alleviating, or reducing the risk of a condition in a subject for which enhanced activity of metabotropic glutamate receptors is desired by administering a therapeutically effective amount of a composition described herein. The term "enhancing amount" refers to the amount of mGluR agonist that, when administered in combination with an effective amount of a compound of the present disclosure, is effective to treat the neurological and psychiatric disorders described herein. It is contemplated that the enhancing amount will be less than the amount of mGluR agonist that would be required to achieve the same effect if the mGluR agonist were administered without the use of an effective amount of a compound of the present disclosure. The attending diagnostician, as one skilled in the art, can readily determine the enhancing amount by the use of routine techniques and observation of results obtained under similar circumstances. In determining the enhancing amount, i.e., the dosage of mGluR agonist to be administered in combination with a composition described herein, the attending diagnostician will take into account a number of factors, including but not limited to: the mGluR agonist selected for administration, including its potency and selectivity; the composition described herein to be administered in combination; the species of mammal; its size, age, and general health; the particular disorder involved; the degree or severity of the disorder; the individual patient's response to treatment; mode of administration; the bioavailability characteristics of the preparation administered; the dosage regimen selected; the use of other concomitant medication; and other relevant circumstances.

[0108] In some embodiments, the compositions described herein can be administered as positive allosteric modulators of metabotropic glutamate receptor type II. In some embodiments, the compositions described herein can be administered as agonists of metabotropic glutamate receptor type II. In some embodiments, the compositions described herein can be administered as antagonists of metabotropic glutamate receptor type II.

[0109] In some embodiments, the present disclosure provides methods of treating, preventing, managing, alleviating, or ameliorating a neurological or psychiatric disorder associated with glutamate dysfunction. In some embodiments, the neurological or psychiatric disorder associated with glutamate dysfunction includes one or more of the following conditions or diseases: acute neurological and psychiatric disorders, such as cerebral dysfunction following heart bypass surgery and transplantation, stroke, cerebral ischemia, spinal cord trauma, head trauma, perinatal hypoxia, stress, cardiac arrest, hypoglycemic neuronal damage, dementia including dementia of the AIDS patients, Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, ocular damage, retinopathy, cognitive disorders, idiopathic and drug-induced Parkinson’s disease, muscle spasticity and disorders associated with muscle spasticity including tremor, epilepsy, convulsions, migraine (including migraine headache), urinary incontinence, disorders associated with substance tolerance, disorders associated with substance withdrawal (including opiate, nicotine, tobacco, alcohol, benzodiazepines, cocaine, sedative, hypnotic, etc. substances), psychosis, schizophrenia, anxiety (including generalized anxiety disorder, panic disorder, and obsessive compulsive disorder), mood disorders (including depression, mania, bipolar disorder), trigeminal neuralgia, hearing loss, tinnitus, ocular macular degeneration, emesis, brain edema, pain (including acute and chronic pain states, severe pain, intractable pain, neuropathic pain, and post-traumatic pain), tardive dyskinesia, sleep disorders (including narcolepsy), attention deficit / hyperactivity disorder, and conduct disorder.

[0110] In some embodiments, the methods and uses of treating, preventing, alleviating, modulating, or ameliorating mood disorders in a subject can include administering an effective amount of a compound or composition described herein. In some embodiments, administering a therapeutically effective amount of a compound includes orally administering the compound. As used herein, the term “mood disorder” encompasses psychological and physical diseases and conditions recognized and understood by medical practitioners in the relevant medical field. A mood disorder can include one or more psychological / physiological symptoms that significantly affect an individual’s emotional state and daily functioning. For example, symptoms of a mood disorder can manifest as prolonged sadness or depression, loss of interest in once enjoyed activities, significant changes in appetite or weight, sleep disturbances, fatigue, feelings of worthlessness or excessive guilt, and, in severe cases, thoughts of death or suicide. Mood disorders can result in difficulties maintaining interpersonal relationships, work performance, and participation in social activities. The compounds according to the present disclosure can provide a natural compound that is safe and effective in alleviating anxiety. In some embodiments, the therapeutic efficacy of the compounds according to the present disclosure can be more effective or less effective depending on the severity or type of mood disorder.

[0111] In some embodiments, methods and uses for treating, preventing, reducing, modulating, or ameliorating sleep disorders in a subject can include administering an effective amount of a compound or composition described herein. In some embodiments, administering a therapeutically effective amount of a compound includes orally administering the compound. Orally administering the compound can include ingesting a natural product in which the compound is a naturally occurring constituent, an enriched natural product, and a substantially pure composition of a compound according to the present disclosure. As used herein, the term “sleep disturbance” encompasses psychological and physical diseases and conditions as recognized and understood by medical practitioners in the relevant medical field. Treating sleep disturbance can include addressing one or more of a variety of symptoms that can affect quality of life and overall health. Individuals with sleep disturbance can experience difficulty falling asleep (insomnia), frequent awakenings during the night, waking up too early and being unable to fall back asleep, or non-restorative sleep (feeling unrefreshed upon waking). Other symptoms include excessive daytime sleepiness, difficulty concentrating, mood changes (such as increased irritability or anxiety), and decreased performance at work or school. In more severe cases, sleep disturbance can also manifest as a sleep disorder, such as sleep apnea (characterized by abnormal breathing patterns) or restless leg syndrome (a feeling of discomfort and an irresistible urge to move the legs while trying to fall asleep). Compounds according to the present disclosure can provide a natural compound that safely and effectively protects sleep and the circadian rhythm. In some embodiments, the efficacy of a compound according to the present disclosure can be more effective or less effective depending on the severity or type of sleep disturbance. In some embodiments, a compound according to the present disclosure can treat sleep disorders independent of a stressor.

[0112] In some embodiments, the compositions of the present disclosure can also be used in methods for preventing, treating, managing, alleviating, or reducing the risk of the diseases, disorders, and conditions described above in combination with other agents, including mGluR agonists. In some embodiments, the present disclosure provides methods for treating, preventing, managing, or alleviating a disease or condition associated with mGlu2 receptors by administering to a subject in need thereof a therapeutically effective amount of a composition described herein. In some embodiments, the present disclosure provides methods for treating, preventing, managing, or alleviating a disease or condition associated with mGlu3 receptors by administering to a subject in need thereof a therapeutically effective amount of a composition described herein.

[0113] In some embodiments, the present disclosure provides methods of treating anxiety in a subject by administering an effective amount of a composition described herein. In some embodiments, the anxiety is a generalized anxiety disorder. In some embodiments, the anxiety disorder is caused by a general medical condition. In some embodiments, the anxiety is caused by a substance-induced anxiety disorder. As used herein, the term "anxiety" includes treatment of anxiety disorders and related conditions described in the DSM-IV. Those skilled in the art will recognize that there are different nomenclatures, disease classifications, and classification systems for neurological and psychiatric disorders, particularly anxiety, and that these systems evolve as the science of medicine advances. Thus, the term "anxiety" is intended to encompass similar conditions described in other diagnostic sources. In some embodiments, the subject's anxiety is alleviated by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25.0%, 50.0%, 75.0%, or a range including and / or spanning the aforementioned values. In some embodiments, the methods and uses of treating, preventing, alleviating, modulating, or ameliorating anxiety in a subject can comprise administering an effective amount of a compound or composition described herein. In some embodiments, administering a therapeutically effective amount of a compound comprises orally administering the compound. Orally administering the compound can comprise ingesting a natural product in which the compound is a naturally occurring constituent, an enriched natural product, and a composition of the compound substantially pure according to the present disclosure.

[0114] In another embodiment, the present disclosure provides methods of treating anxiety comprising: administering to a patient in need thereof an effective amount of a compound or composition described herein. In some embodiments, conditions associated with anxiety include, but are not limited to, panic disorder with or without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, anxiety disorder due to a general medical condition, substance-induced anxiety disorder, and anxiety disorder not otherwise specified.

[0115] In some embodiments, the present disclosure provides methods of treating depression in a subject resulting from stress by administering an effective amount of a composition described herein. Currently, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-V) (2022, American Psychiatric Association, Washington, D.C.) provides a diagnostic tool that includes depressive and related disorders. Depressive disorders include, for example, single or recurrent major depressive disorder, dysthymic disorder, depressive neurosis, and neurotic depression; melancholic depression, including anorexia, weight loss, insomnia and early morning awakening, and psychomotor retardation; atypical depression (or reactive depression), including increased appetite, somnolence, psychomotor agitation or irritability, anxiety, and phobias; seasonal affective disorder; or bipolar disorder or manic-depressive illness, for example, bipolar I disorder, bipolar II disorder, and cyclothymic disorder. As used herein, the term “depression” includes treatment of depressive and related disorders described in the DSM-IV. In some embodiments, the depression in the subject resulting from stress is alleviated by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25.0%, 50.0%, 75.0%, or a range including and / or spanning the aforementioned values.

[0116] In some embodiments, the present disclosure provides methods of treating schizophrenia in a subject by administering an effective amount of a composition described herein. The Merck Manual (2006-2007) indicates that schizophrenia is characterized by disorganized thinking (disconnection from reality), hallucinations (false perceptions), delusions (false beliefs), speech and behavior disturbances, affective flattening (restricted range of emotions), cognitive deficits (impaired reasoning and problem solving), and impairment in occupational and social functioning. In some embodiments, the schizophrenia in the subject is alleviated by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25.0%, 50.0%, 75.0%, or a range including and / or spanning the aforementioned values.

[0117] In some embodiments, the present disclosure provides methods of treating panic disorder in a subject by administering an effective amount of a composition described herein. In some embodiments, the panic disorder is accompanied by agoraphobia. In some embodiments, the panic disorder is not accompanied by agoraphobia. In some embodiments, the panic disorder in the subject is alleviated by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25.0%, 50.0%, 75.0%, or a range including and / or spanning the aforementioned values.

[0118] In some embodiments, the present disclosure provides methods of treating post-traumatic stress disorder (PTSD) in a subject by administering an effective amount of a composition described herein. In some embodiments, the subject's PTSD is ameliorated by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25.0%, 50.0%, 75.0%, or a range including and / or spanning the aforementioned values.

[0119] The methods described herein can also include identifying a patient having a disease or condition described herein. In some embodiments, the method further includes identifying a subject having a condition in which metabotropic glutamate receptor activity is desired to be enhanced. In some embodiments, the method further includes identifying a subject having a neurological or psychiatric disorder associated with glutamate dysfunction. In some embodiments, the method further includes identifying a subject having a disease or disorder associated with mGlu2 receptors. In some embodiments, the method further includes identifying a subject having a disease or disorder associated with mGlu3 receptors. In some embodiments, the method further includes identifying a subject having generalized anxiety disorder. In some embodiments, the method further includes identifying a subject having depression. In some embodiments, the method further includes identifying a subject having schizophrenia. In some embodiments, the method further includes identifying a subject having panic disorder. In some embodiments, the method further includes identifying a subject having post-traumatic stress disorder (PTSD). In some embodiments, identifying a subject includes collecting a sample from the patient. In some embodiments, identifying a subject includes isolating a sample from the subject. In some embodiments, isolating a sample from the subject is isolating DNA from the subject. In some embodiments, the method further includes determining whether the patient has the disease or condition.

[0120] In some embodiments, methods and uses of modulating metabotropic glutamate receptors are provided. In some embodiments, the methods and uses include providing one or more compounds of Table A or a composition comprising one or more compounds of Table A. In some embodiments, the metabotropic glutamate receptors include metabotropic glutamate receptor type II. In some embodiments, the metabotropic glutamate receptors include one or more compounds capable of acting as an antagonist of metabotropic glutamate receptor 2 and / or metabotropic glutamate receptor 3. In some embodiments, the metabotropic glutamate receptors include one or more compounds capable of acting as an agonist of metabotropic glutamate receptor 2 and / or metabotropic glutamate receptor 3.

[0121] In some embodiments, the methods and uses of the present disclosure include maintaining a healthy stress response. In some embodiments, the methods and uses include providing one or more compounds of Table A or a composition described herein. In some embodiments, the composition described herein is formulated for oral administration. In some embodiments, the dosage form of the composition is configured as one of a soft gel capsule, a hard gel capsule, a gummy, a functional beverage, a functional food, a liquid, a powder, and a tablet. In some embodiments, the composition comprises 1.0% to 99% w / w of a plant extract described herein. In some embodiments, the composition further comprises a carrier, a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof. In some embodiments, the composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutraceutical, or a pharmaceutical composition. In some embodiments, an oral composition for a medicament intended to maintain a healthy stress response or a condition thereof comprises one or more compounds of Table A. In some embodiments, a composition is used to maintain a healthy stress response in a subject, wherein the composition comprises one or more compounds of Table A.

[0122] In some embodiments, the methods and uses of the present disclosure include maintaining glutamate homeostasis. In some embodiments, the methods and uses include providing one or more compounds of Table A or a composition described herein. In some embodiments, the composition described herein is formulated for oral administration. In some embodiments, the dosage form of the composition is configured as one of a soft gel capsule, a hard gel capsule, a gummy, a functional beverage, a functional food, a liquid, a powder, and a tablet. In some embodiments, the composition comprises 1.0% to 99% w / w of a plant extract described herein. In some embodiments, the composition further comprises a carrier, a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof. In some embodiments, the composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutraceutical, or a pharmaceutical composition. In some embodiments, an oral composition for a medicament intended to maintain glutamate homeostasis or a condition thereof comprises one or more compounds of Table A. In some embodiments, a composition is used to maintain glutamate homeostasis in a subject, wherein the composition comprises one or more compounds of Table A.

[0123] In some embodiments, methods and uses for modulating stress are provided. In some embodiments, the methods and uses comprise providing one or more compounds of Table A or a composition described herein. In some embodiments, the composition described herein is formulated for oral administration. In some embodiments, the dosage form of the composition is configured as one of a soft capsule, a hard capsule, a gummy, a functional beverage, a functional food, a liquid, a powder, and a tablet. In some embodiments, the composition comprises 1.0% to 99% w / w of a plant extract described herein. In some embodiments, the composition further comprises a carrier, a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof. In some embodiments, the composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutraceutical, or a pharmaceutical composition. In some embodiments, an oral composition for a medicament intended to modulate stress or a condition thereof comprises one or more compounds of Table A. In some embodiments, a composition is used to modulate stress in a subject, wherein the composition comprises one or more compounds of Table A.

[0124] In some embodiments, methods and uses for emotional support are provided. In some embodiments, the methods and uses comprise providing one or more compounds of Table A or a composition described herein. In some embodiments, the composition described herein is formulated for oral administration. In some embodiments, the dosage form of the composition is configured as one of a soft capsule, a hard capsule, a gummy, a functional beverage, a functional food, a liquid, a powder, and a tablet. In some embodiments, the composition comprises 1.0% to 99% w / w of a plant extract described herein. In some embodiments, the composition further comprises a carrier, a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof. In some embodiments, the composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutraceutical, or a pharmaceutical composition. In some embodiments, an oral composition for a medicament intended to provide emotional support or to ameliorate a condition thereof comprises one or more compounds of Table A. In some embodiments, a composition is used to provide emotional support to a subject, wherein the composition comprises one or more compounds of Table A.

[0125] Accordingly, some aspects described herein relate to the following numbered options:

[0126] 1. An oral composition for treating, reducing, modulating, or alleviating stress, a symptom of stress, or a deleterious effect of chronic stress, the oral composition comprising: a therapeutically effective amount of a plant extract; and one or more carriers or excipients, wherein the therapeutically effective amount of the plant extract is capable of treating, reducing, modulating, or alleviating stress, a symptom of stress, or a deleterious effect of chronic stress.

[0127] 2. The oral composition according to option 1, wherein the plant extract comprises a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-1- benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloe-emodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a- decahydroazulen-4-yl methyl acrylate, or a combination thereof.

[0128] 3. The oral composition according to option 1 or 2, wherein the oral composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutritional composition, or a pharmaceutical composition.

[0129] 4. The oral composition according to any one of options 1 to 3, wherein the dosage form of the oral composition is configured as one of a soft gel capsule, a hard gel capsule, a liquid, a powder, and a tablet.

[0130] 5. The oral composition according to any one of options 1 to 4, wherein the oral composition comprises 10% to 99% w / w of the plant extract.

[0131] 6. The oral composition according to any one of options 1 to 5, wherein the plant extract further comprises a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof.

[0132] 7. A method of treating, preventing, reducing, modulating, or alleviating the deleterious effects of stress, a symptom of stress, or chronic stress in a subject in need thereof, the method comprising administering a therapeutically effective amount of a composition comprising the oral composition according to any one of options 1 to 6.

[0133] 8. The method according to option 7, wherein the plant extract of the oral composition is capable of activating a metabotropic receptor type II.

[0134] 9. The method according to option 7 or 8, wherein the plant extract activates the mGlu2 receptor.

[0135] 10. The method according to option 7 or 8, wherein the plant extract activates the mGlu3 receptor.

[0136] 11. An oral composition comprising: a plant extract that is an mGlu2 or mGlu3 receptor antagonist; and one or more carriers or excipients.

[0137] 12. The oral composition according to option 11, wherein the plant extract is selected from the group consisting of rhubarb, emblica, cacao, or a combination thereof.

[0138] 13. The oral composition according to any of options 11 or 12, wherein the plant extract comprises a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-1- benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4- ylmethyl acrylate, or a combination thereof.

[0139] 14. The oral composition according to any of options 11 to 13, wherein the oral composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutritional composition, or a pharmaceutical composition.

[0140] 15. The oral composition according to any of options 11 to 14, wherein the dosage form of the oral composition is configured as one of a soft capsule, a hard capsule, a liquid, a powder, and a tablet.

[0141] 16. The oral composition according to any of options 11 to 15, wherein the oral composition comprises 10% to 99% w / w of the plant extract.

[0142] 17. The oral composition according to any of options 11 to 16, wherein the plant extract further comprises a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof.

[0143] 18. An oral composition comprising: a plant extract that is a mGlu2 or mGlu3 receptor agonist or positive allosteric modulator; and one or more carriers or excipients.

[0144] 19. The oral composition according to option 18, wherein the plant extract is selected from the group consisting of Radix Tripterygii, Emblica officinalis, Hypericum perforatum, Aloe barbadensis, Hypericum perforatum, or a combination thereof.

[0145] 20. The oral composition according to any of options 18 or 19, wherein the plant extract comprises a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-1- benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4- ylmethyl acrylate, or a combination thereof.

[0146] 21. An oral composition according to any one of options 18 to 20, wherein the oral composition is formulated as a dietary supplement, food ingredient or additive, medical food, nutritional composition or pharmaceutical composition.

[0147] 22. An oral composition according to any one of options 18 to 21, wherein the dosage form of the oral composition is configured as one of soft capsules, hard capsules, liquids, powders, and tablets.

[0148] 23. An oral composition according to any one of options 18 to 22, wherein the oral composition comprises 10% to 99% w / w of a plant extract.

[0149] 24. An oral composition according to any one of options 18 to 23, wherein the plant extract further comprises a preservative, a sweetener, a coloring agent, an additive, a flavoring agent, or a combination thereof.

[0150] 25. A method of regulating a disease or condition associated with mGlu2 / 3, comprising: administering to a subject in need a therapeutically effective amount of an oral composition according to any one of options 18 to 24.

[0151] 26. An oral composition for inhibiting mGlu2 or mGlu3, the composition comprising a plant extract selected from rhubarb, cocoa, barley, papaya, pitcher plant (Nepenthes hognata), small-fruited banana, Douglas fir (Pseudotsugamenziesii var. menziesii), valerian leaf willow, pea, African aloe, soybean, oat, apple, gardenia, Cape aloe, rice, small-grain coffee, safflower, hard-skinned bean, eggplant, aloe vera, Satsuma mandarin orange, St. John's wort, turmeric, water coconut, and ryegrass cereale cv. Aroostook, indigo, cannabis, tomato, cremantin, red clover, uncaria rhynchophylla, guarana, sweet orange, cycad, bitter melon, dragon bone mustard, gaillardia, lotus, black radish, Inca radish, corn, tobacco, ochre mushroom, flax, peony, chili pepper, tridentate oak, four o'clock flower, periwinkle or combinations thereof; and one or more carriers or excipients.

[0152] 27. The oral composition according to alternative embodiment 26, wherein the plant extract comprises a compound selected from (2S)-2α-(4-hydroxyphenyl)-2H-1-benzopyran-7-ol, guibourtinidol, frangula-emodin, aloe-emodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazolo[6,5-b]furan-4-ylmethacrylate or combinations thereof.

[0153] 28. The oral composition according to any of options 26 or 27, wherein the oral composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutritional composition, or a pharmaceutical composition.

[0154] 29. The oral composition according to any of options 26 to 28, wherein the dosage form of the oral composition is configured as one of a soft capsule, a hard capsule, a liquid, a powder, and a tablet.

[0155] 30. The oral composition according to any of options 26 to 29, wherein the oral composition comprises 10% to 99% w / w of the plant extract.

[0156] 31. The oral composition according to any of options 26 to 30, wherein the plant extract further comprises a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof.

[0157] 32. A method of treating or modulating a disease or condition associated with mGlu2 or mGlu3, comprising: administering to a subject in need thereof a therapeutically effective amount of the oral composition according to any of options 26 to 31.

[0158] 33. An oral composition for activating mGlu2 or mGlu3, the composition comprising a plant extract selected from Momordica charantia, Aloe vera, Silybum marianum, Aloe ferox, Rheum officinale, Chaenomeles speciosa, Citrus aurantium, Hordeum vulgare, Erucastrum gallicum, Linum usitatissimum, Cynanchum syriacum, Hypericum perforatum, Koompassia excelsa, Eucalyptus binervis, Emblica officinalis, Leucophyllum frutescens, Malva sylvestris, Melastoma affine, Morinda citrifolia, Papaver somniferum, Podocarpus spicatus, Tripterygium wilfordii, Aloe arborescens, Juniperus chinensis, Lentinula edodes, Gypsophila perfoliata, Melicope pellita, Panax notoginseng, Rosmarinus officinalis, Nelumbo nucifera, Citrus unshiu, Polytrichum commune, Citrus sinensis, Juniperus communis, Forsythia suspensa, or a combination thereof; and one or more carriers or excipients.

[0159] 34. The oral composition according to option 33, wherein the plant extract comprises a compound selected from (2S)-2a-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloe-emodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydropicen[6,5-b]furan-4-yl methyl acrylate, or a combination thereof.

[0160] 35. An oral composition according to option 33 or 34, wherein the oral composition is formulated as a dietary supplement, food ingredient or additive, medical food, nutritional composition or pharmaceutical composition.

[0161] 36. An oral composition according to any one of options 33 to 35, wherein the dosage form of the oral composition is configured as one of soft capsules, hard capsules, liquids, powders, and tablets.

[0162] 37. An oral composition according to any one of options 33 to 36, wherein the oral composition comprises 10% to 99% w / w of a plant extract.

[0163] 38. An oral composition according to any one of options 33 to 37, wherein the plant extract further comprises a preservative, a sweetener, a coloring agent, an additive, a flavoring agent, or a combination thereof.

[0164] 39. A method of treating or regulating a disease or condition associated with mGlu2 or mGlu3, comprising: administering to a subject in need a therapeutically effective amount of an oral composition according to any one of options 33 to 38.

[0165] 40. An oral composition having enhanced binding affinity and increased activity, the composition comprising a plant extract selected from Medicago sativa subsp. sativa, Solanum nigrum, small-grain coffee, bitter melon, aloe vera, milk thistle, cocoa, Cape aloe, gardenia, cashew, capsicum, peony, rhubarb, papaya, Clementine, barley, Erucastrum gallicum, flax, Syrian milkweed, oats, St. John's wort, turmeric, corn, three-toothed sagewood, tobacco, Eucalyptus globulus, small-fruited banana, eggplant, amla, tomato, Veronica persica, hollyhock, star vine, jade tree, lemon, periwinkle, four o'clock flower, Podocarpus spicatus, Tripterygium wilfordii, honeysuckle bean, African aloe, Crinum asiaticum, Juniperus chinensis, Pleurotus ostreatus, Gypsophila perfoliate, false wampee, creeping chrysanthemum, red clover, rice, rosemary, lotus, safflower, Wenzhou mandarin orange, sphagnum moss, sweet orange, Juniperus chinensis, forsythia or combinations thereof; and one or more carriers or excipients.

[0166] 41. The oral composition according to option 40, wherein the plant extract comprises a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-1- benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloe-emodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a- decahydropicen[6,5-b]furan-4-ylmethyl acrylate, or a combination thereof.

[0167] 42. The oral composition according to option 40 or 41, wherein the oral composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutritional composition, or a pharmaceutical composition.

[0168] 43. The oral composition according to any one of options 40 to 42, wherein the dosage form of the oral composition is configured as one of a soft gel capsule, a hard gel capsule, a liquid, a powder, and a tablet.

[0169] 44. The oral composition according to any one of options 40 to 43, wherein the oral composition comprises 10% to 99% w / w of the plant extract.

[0170] 45. The oral composition according to any one of options 40 to 44, wherein the plant extract further comprises a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof.

[0171] 46. A method of treating or modulating a disease or condition associated with mGlu2 or mGlu3, comprising: administering to a subject in need thereof a therapeutically effective amount of the oral composition according to any one of options 40 to 45.

[0172] 47. A method of treating, preventing, reducing, modulating, or alleviating anxiety in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of an mGlu2 receptor antagonist, an mGlu3 receptor antagonist, or a combination thereof; and a carrier.

[0173] 48. A method of treating, preventing, reducing, modulating, or ameliorating anxiety in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4-yl methyl acrylate, or combinations thereof; and a carrier.

[0174] 49. A method of treating, preventing, reducing, modulating, or ameliorating the negative effects of emotional stress on sleep in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4-yl methyl acrylate, or combinations thereof; and a carrier.

[0175] 50. A method of treating, preventing, reducing, modulating, or ameliorating the negative effects of emotional stress on sleep in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of an mGlu2 receptor antagonist, an mGlu3 receptor antagonist, or combinations thereof; and a carrier.

[0176] 51. A method of treating, preventing, reducing, modulating, or ameliorating the negative effects of circadian rhythm in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of (2S)-2a-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4-yl methyl acrylate, or combinations thereof; and a carrier.

[0177] 52. A method of treating, preventing, reducing, modulating or ameliorating the negative effects of circadian rhythm in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of an mGlu2 receptor antagonist, an mGlu3 receptor antagonist, or a combination thereof; and a carrier.

[0178] 53. A method of treating, preventing, reducing, modulating or ameliorating the negative effects of mood in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of (2S)-2α-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4-yl methyl acrylate, or a combination thereof; and a carrier.

[0179] 54. A method of treating, preventing, reducing, modulating or ameliorating the negative effects of mood in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of an mGlu2 receptor antagonist, an mGlu3 receptor antagonist, or a combination thereof; and a carrier.

[0180] 55. A method of treating, preventing, reducing, modulating or ameliorating sleep disturbances in a subject, the method comprising: providing to the subject a composition comprising a compound selected from the group consisting of (2S)-2α-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4-yl methyl acrylate, or a combination thereof; and a carrier.

[0181] 56. An oral composition for a medicament intended to treat stress, anxiety, sleep disturbances, or related conditions thereof, comprising a compound selected from the group consisting of (2S)-2α-(4-hydroxyphenyl)-2H-l-benzopyran-7-ol, guibourtinidol, Frangula-emodin, aloemodin, (3aR,4aR,7aR,8R,9aR)-4a,8-dimethyl-3-methylene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazulen-4-yl methyl acrylate, or a combination thereof; and a carrier.

[0182] Example

[0183] The following embodiments illustrate protocols and methods for validating and demonstrating the activity of the compounds of this disclosure in treating or alleviating one or more of the conditions described herein. In some embodiments, experiments may demonstrate or assess whether one or more compounds of this disclosure reduce the negative effects of emotional stress on sleep, circadian rhythms, and mood. One or more compounds of this disclosure may be administered orally to a subject, for example, in the form of a nutritional supplement. In some embodiments, methods and procedures may be performed on rodents (e.g., mice or rats) according to the following embodiments. If applicable, experiments may be designed and conducted under the supervision of the Animal Care and Use Committee (ACUC) to test the efficacy of oral supplements in reducing stress responses in rodents. For example, the committee may assist in ensuring that research protocols involving animals comply with ethical standards and minimize animal discomfort, anxiety, and distress. Depending on the compound under investigation, rigorous in vivo preclinical trials should be conducted prior to clinical trials. As described below, such in vivo preclinical trials may include monitoring a validated rat model of emotional stress using in vivo biotelemetry tools and infrared video cages.

[0184] Example 1

[0185] Using Dionex TM Plant material was extracted using an accelerated solvent extractor 350. 25g of ground plant tissue was loaded into four 100mL stainless steel ASE extraction tanks. The preset temperature was 60℃, and static extraction was performed for twelve cycles. The solvents used for extraction were 95% ethanol, ethyl acetate, and hexane. After solvent removal, the 95% ethanol extract was subjected to a bioassay-guided fractionation protocol. In short, the extract was dry-loaded onto a C18 spherical rapid column chromatography. Elution was performed using a mobile phase consisting of water + 0.1% formic acid (A) and CH3CN + 0.1% formic acid (B), following a gradient: from 1% to 3% B within 3 minutes, to 100% B within 22 minutes, and then maintained at 100% B for 7 minutes at a flow rate of 30mL / min. The highly active fractions were combined and then further purified using Kinetex reversed-phase C18 preparative chromatography via bioassay-guided fractionation to obtain guibourtinidol.

[0186] Example 2

[0187] This is a forward-looking embodiment. In this embodiment, the plant tissues in Table 1 are extracted using the method of Example 1.

[0188] Table 1

[0189]

[0190]

[0191]

[0192]

[0193]

[0194]

[0195]

[0196]

[0197]

[0198]

[0199]

[0200]

[0201]

[0202]

[0203]

[0204]

[0205]

[0206]

[0207]

[0208]

[0209]

[0210]

[0211] The amount of guibourtinidol or other compounds of interest (such as those described herein) present in certain extracts was determined (percent of extract, w / w). Compounds were quantified by normalizing the results to the weight of the extract. These analytical results were determined.

[0212] Example 3

[0213] An oral composition for daily consumption is provided in the form of a capsule comprising guibourtinidol from Cassia abbreviate extract and a carrier.

[0214] INDICATION: As an oral composition, administer 1 capsule orally once daily, with 8 ounces of water.

[0215] Example 4

[0216] In this example, plant fractions were isolated and tested to confirm antagonistic or inhibitory activity.

[0217] A Dionex TM Accelerated Solvent Extractor TM (“ASE”) 350 was used to extract plant material. 5 g of lyophilized ground plant tissue was loaded into a 25 mL stainless steel ASE extraction cell. The pre-set temperature was 60 °C and five extraction cycles were performed for each cell: 2 x 95% ethanol (AX), 1 x 1 : 1 95% ethanol: ethyl acetate (BX), 1 x ethyl acetate (CX), and 1 x hexane (DX). A 3 mL aliquot was taken from each of the AX, BX, CX, and DX extracts and dried using a vacuum concentrator (HT12 3i series, SP Scientific). One additional 3 mL AX extract aliquot was treated with 0.5 g of polyvinylpyrrolidone (PVP) resin to make an additional sample (AP). The resin was filtered out using a centrifugal filter device (PVDF, 0.45 pm) and the remaining supernatant was dried using a vacuum concentrator. To generate the X0-X6 fractions, the AX, BX, CX, and DX extracts were combined, adsorbed onto celite, and loaded into a solid loading column for C18 spherical flash chromatography fractionation on a Combi Flash (Teledyne). Fractionation was performed using a mobile phase consisting of water + 0.1% formic acid (A) and CH3CN + 0.1% formic acid (B) at a flow rate of 18 mL / min. For each isocratic elution step, two minute fractions were collected with increasing polarity (10%, 20%, 40%, 60%, 80%, 100% B for X0, X1, X2, X3, X4, X5, respectively), and an additional 4 minute 100% B fraction was collected as the X6 fraction.

[0218] The agonist, positive allosteric modulator (PAM), and antagonist / negative allosteric modulator (NAM) activities of mGluR2 and mGluR3 were measured in the samples. Preliminary assays of mGluR2 and mGluR3 activities were performed using the DiscoverX-designed and supplied cAMPHitHunter® assay, with mGluR2 and mGluR3 assays performed on CHO-K1 GRM2 Gi and CHO-K1GRM3 Gi cell lines, respectively. The assay protocol was adjusted to assess differences in activity directionality, and the same assay protocol was used for both mGluR2 and mGluR3 assays. For agonist activity, the assay was performed without the addition of any internal agonist, and the effect on receptor activity was measured. For PAM activity, the assay was performed with the addition of a known control agonist, LY354740, at a concentration of 10 nM. Finally, to determine antagonist / NAM activity, the assay was performed with the addition of the same known control agonist, at a concentration of 50 nM. Since both antagonist and NAM activities require the addition of an agonist, screening assays cannot distinguish between antagonist and NAM activities. Western blotting analysis of phosphorylation of the downstream component ERK (pERK) in the signal cascade confirmed the activity of the receptor of interest. The assay conditions employed the same differentiation strategy as described above, namely, adding different concentrations of a control agonist to samples that showed the corresponding activity in the initial assay. Agonist and PAM activities increased pERK, while antagonist / NAM activities decreased pERK.

[0219] To address any potential activity concerns regarding assay performance and possible toxicity issues in future in vivo testing, cellular metabolic health, cell viability, and live / dead analysis (a measure of cell death) were also performed on samples demonstrating mGluR2 and mGluR3 activity. CyQUANT, provided by ThermoFisher, was used. TM The XTT assay kit was used to measure cell viability, and the HCS Live / Dead Green kit provided by Invitrogen was used to measure the live / dead ratio.

[0220] The research results are shown in Tables 2 to 6 and Figures 1 to 2 The description is in the middle.

[0221] Table 2

[0222]

[0223] Table 3

[0224]

[0225] *PAM – Positive Allosteric Modifier

[0226] Table 4

[0227]

[0228]

[0229]

[0230]

[0231]

[0232] Table 5

[0233]

[0234]

[0235]

[0236]

[0237] Table 6

[0238]

[0239]

[0240]

[0241]

[0242]

[0243]

[0244] Example 5

[0245] This example describes in vitro data for compounds of the disclosure in a standardized biological assay protocol.

[0246] According to the procedures outlined in Figure 3The standardised bioassay protocol shown was followed. In the standardised bioassay protocol, HBSS assay buffer containing 1% HEPES was used. Cells were plated at 10,000 cells / well in 20 mΐ plating reagent overnight. Controls for the experiment were L-glutamate agonist (AC1562 1250), LY354740 agonist (fischer part number #32-465-0), LY341495 antagonist (fischer part number #12-095-0), PAM for BINA (fischer part number #40-485-0), and NAM for decoglurant (fischer part number #50-203-0742).

[0247] Results are shown in Table 7 and Figure 4 , Figure 5 Figure 4 showing mGlu2 activity higher than control (100% in red dotted line) indicates mGlu2 negative allosteric modulator or antagonist. The assay was performed at 20 mM concentration. Figure 5 showing mGlu2 activity lower than control (100%) indicates mGlu2 positive allosteric modulator or agonist. The assay was performed at 100 mM concentration.

[0248] Table 7

[0249]

[0250] Example 6

[0251] This example describes the study protocol for testing the tolerability and efficacy of a novel plant-derived supplement on sleep disturbances and anxiety.

[0252] Background and Objectives

[0253] Emotional and physical stress can disrupt sleep and circadian rhythms and increase the risk of developing mood disorders. Given the recent evidence that repeated or long-term use of sedative-hypnotic prescription or over-the-counter sleep aids can have negative effects on brain health, there is a need to develop new natural compounds that are safe and effective in reducing emotional stress and protecting sleep and circadian rhythms. The main objective of this example is to test the hypothesis that oral administration of the nutraceutical of the present disclosure reduces the negative effects of emotional stress on sleep, circadian rhythms, and mood.

[0254] Primary Objective - Study 1 : Maximum Tolerated Dose (MTD) Study

[0255] ​Rats will be tested for tolerance to two potential compounds of the disclosure. Compounds will be administered via oral gavage. Rats will be administered compounds once daily for 4 days. Doses will be dependent on pharmacological profile. Other dependent variables will be in accordance with published MTD guidelines. Body weight and food intake will be measured daily. At the end of the study, rats will be sacrificed and their tissues dissected, examined, weighed, and frozen for possible future toxicology-related analyses. Continuous infrared video home cage monitoring will capture behavioral changes, including sickness behavior. Results of this work will help determine the MTD for each compound to be tested in the efficacy “Stress and BioTelemetry” study described below.

[0256] Experimental Design

[0257] 2x2 (male, female) x 4 to 7 doses + vehicle: 16 to 28 groups, with an estimated number of rats of 160 to 280, depending on the MTD range. Rats will be orally administered vehicle (vehicle) or one compound of the disclosure daily for 5 consecutive days, shortly after the start of the inactive / sleeping period (0900). Due to the labor-intensive nature of this project, multiple balanced cohorts will be tested on staggered start dates. Study length: 18 days (14 days of animal room acclimation, 4 days of oral administration of vehicle and compounds) x 4 groups ~ 20 weeks.

[0258] Experiment 2: Efficacy Study: Stress and BioTelemetry

[0259] A daily oral compound of the disclosure will be tested daily and the negative effects of chronic emotional stress on sleep, circadian rhythms, and anxiety will be measured using the rat CCF model of chronic emotional stress described below. The maximum tolerated dose (MTD) of a compound of the disclosure will be tested and based on the MTD study described above. Chronic conditional fear (CCF) is a well-validated model of sustained emotional stress that has been previously reported to result in a range of maladaptive consequences, starting with sleep dysregulation, circadian flattening, and anxiety-like behaviors. In vivo bio telemetry and infrared Synology home cage monitoring will be used to collect dependent variables. Rats will be randomly assigned to be exposed to a chronic conditional fear protocol (CCF) or left in the home cage as non-stressed controls.

[0260] All rats will be surgically implanted with HD-S02emitters for biotelemetry, which allows for the measurement of locomotor activity (LA), heart rate (HR), core body temperature (CBT), nuchal dorsal muscle electromyography (EMG), and electroencephalography (EEG). For this project, rats will be instrumented with telemetry to measure LA, CBT, EMG, and EEG. Following recovery from surgery, continuous biotelemetry measurements will be collected prior to CCF (24 hours per day for 3 days, home cage recordings), during CCF (20 minutes per session, 2 sessions per day of CF training for 21 days, fear conditioning chamber), and after CCF (24 hours per day for 7 days, home cage recordings). For this project, both male and female rats will be tested, as there are reports of gender differences in conditioned fear.

[0261] Secondary objectives

[0262] These studies will also explore the potential effects of oral compounds of the present disclosure on behavior and physiology in the absence of stress. The maximum tolerated dose study will include home cage observations to determine the effects of the compounds on home cage behavior. As the stress and biotelemetry studies include non-stressed control groups, this study will also discover any effects of repeated oral compound administration on sleep, in vivo physiology, and behavior.

[0263] Experimental methods setup and feasibility

[0264] Conditioned fear (CF): CF is produced when a rat is conditioned to fear a specific environment by placing the rat in the fear conditioning chamber and applying 3, 2-second, 1.5 mA footshocks. Pairing the footshock with the confinement once will cause the rat to fear the confinement chamber without the need for additional footshocks. This is called “conditioned fear” (CF). Rodents express fear by freezing, which is defined as the absence of movement except for that required for respiration. CF also produces the typical features of the in vivo stress response, including increased heart rate, blood pressure, and core body temperature.

[0265] Chronic conditional fear (CCF): The CCF model is designed to explore the effects of sustained emotional stress on psychology and physiology. For the CCF model, rats are exposed to the conditioning chamber twice daily at random times during their sleep cycle for 20 minutes. Without footshock, after multiple exposures to the chamber, fear behavior will extinguish. If the time spent freezing during a 20-minute test is less than 50%, one “reminder” footshock (2 seconds, 1.5 mA) will restore fear behavior and stress response. Typically only 1 or 2 “reminder” footshocks are needed to maintain fear behavior and stress response for 14 days (2 times per day). The Fleshner Stress Physiology Lab is an expert in this procedure and has previously reported that conditional fear elicits features of stress response in the body, including increases in HR, MAP, CBT, while chronic conditional fear leads to sleep disturbances, blunting of circadian rhythms, and anxiety-like behavior. In humans, repeated sources of psychological stress (such as fear) also increase HR, CBT, and anxiety, thus enhancing the translational power of this model.

[0266] Home cage behavior patterns indicate anxiety, and exposure to the stressor changes home cage behavior patterns, suggesting increased anxiety and depression. Infrared cameras will capture 24-hour video recording home cage behavior. Behavior will be analyzed before, during, and after exposure to the stressor. Changes in anxiety and depression will be captured by analyzing home cage behavior using Behavior Observation Research Interactive Software (BORIS), rather than by open field, forced swim test, or eight-arm maze tasks, as there is evidence that these tests themselves perturb sleep, blunt circadian rhythms, and are influenced by the presence of an observer.

[0267] Methods

[0268] Bio-telemetry (DSI TM ) - in vivo stress response, circadian rhythms, and sleep EEG: Sleep (rapid eye movement REM and non-rapid eye movement NREM) will be measured using EMG and EEG data and analyzed using Neuroscore TM software. Circadian blunting will be captured using LA, EEG, and CBT data and scored using ClockLab program version 6.1.02 (Actimetrics Software TM , Willmette, IL, USA).

[0269] Infrared Synology Home Cage Monitoring: Due to limitations of video equipment and time constraints, the system will be used to video record rats in their home cages during tolerance studies (not stress and biotelemetry studies). This non-invasive procedure will not disturb the animals. Axis Model #M3104 infrared cameras will be placed near the rats' cages to provide 24-hour left-to-right video recording of in-cage behavior. These cameras provide excellent visual resolution of the animals during light and dark cycles without introducing light or disturbing sleep or circadian and physiological rhythms. Synology Surveillance Station will be used to acquire our video recordings. In-cage video recordings will be scored using Behavior Observation Research Interactive Software (BORIS) (Friard and Gamba, 2016). This software allows for the simultaneous scoring of multiple behaviors. Snapshot analysis: In-cage behavior will be scored for 1 hour before lights off and 1 hour after lights off and expressed as a percentage of control (total time spent in specific activity by control animals (vehicle, HCC) / total time spent in specific activity by rats exposed to emotional stress). This time window captures activity induced by the light / dark change. It is known that rats exhibit high levels of spontaneous activity during the first hour after lights off; eating and drinking occur almost exclusively during the dark (active) cycle. Below are detailed descriptions of behaviors (duration, frequency) to be scored according to the Stanford Behavioral Spectrum definitions: Inactive behavior: "No movement" includes periods when the animal is "stationary and alert" and "stationary and unalert (suggesting sleep state)." Overall activity: "Any behavior involving movement." Total duration (and frequency) is scored. Active behavior will also be divided into two subcategories: "Maintenance behavior" or "general activity." Maintenance behavior: behaviors typically used to maintain the animal's physiological stability, comfort, and appearance, including drinking, eating, grooming (self-grooming), and nesting behavior. General activity: other behaviors involving movement that do not fall into the "maintenance behavior" category, including exploratory behavior, affiliative interactions (mutual grooming, wrestling / play), aggressive interactions, and miscellaneous behaviors.

[0270] Expected results: Based on previous research, rats exposed to CCF exhibit sleep / wake behavior, sleep architecture, and disturbances in circadian LA, CBT, and EEG rhythms. The advantages of this experimental approach are as follows: rigorous and reproducible results from the emotional stressor, the conditioned fear (CF), chronic conditioned fear (CCF) model, automated measurement of behavior, physiology, and sleep, real-time, continuous, non-human measurement of fear behavior and in vivo stress physiology, and behavioral methods (24-hour in-cage behavior video recording and BORIS analysis) for determining the emotional / behavioral impact of exposure to the stressor.

[0271] For substantially any plural and / or singular terms used herein, a person skilled in the art can convert plural to singular and / or singular to plural depending on the context and / or applicability. For the sake of clarity, various singular / plural arrangements can be explicitly set forth herein.

[0272] Those skilled in the art will appreciate that, in general, the terms used herein, especially in the appended claims (e.g., in the body of the appended claims), are intended to be interpreted as “open-ended” terms (e.g., the term “comprising” should be interpreted as “including, but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes, but is not limited to,” etc.). Those skilled in the art will further appreciate that, if a specific number is intended in a claim recitation, that intent will be expressly recited in the claim, and in the absence of such recitation there will be no intent to limit the claim to only those embodiments that include the specific number. For example, to help understand, the following appended claims can include the use of introductory phrases such as “at least one” and “one or more” to introduce claim recitations. However, such introductory phrases should not be interpreted as implying that the embodiments so introduced limit the claim to embodiments containing only one such recited embodiment, even though such embodiments are generally included in the claim. For example, the introductory phrase “at least one” should not be interpreted as meaning that the claim limits the claim to only one such recited embodiment, even though such embodiments are generally included in the claim. The same applies to the introductory phrase “one or more.” Even more specifically, even though the introductory phrase “one or more” is used in some claims, it should not be interpreted as meaning that the claim limits the claim to only one such recited embodiment, even though such embodiments are generally included in the claim. This same applies to the use of the definite article “the” to introduce claim recitations. In addition, even though a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the specific number of recitations (e.g., the bare recitation “two recitations” means at least two recitations, or two or more recitations). In addition, those skilled in the art will also recognize that the structure “at least one of A and B” can be interpreted as meaning A or B or both A and B.

[0273] In cases using those in the art convention of“A, B, or C, etc. at least one of,” generally such structure is intended to mean that a convention will be understood by those in the art (e.g.,“a system having at least one of A, B, or C” will include but not be limited to a system that has A alone, or B alone, or C alone, or A and B and / or C, etc.). Those skilled in the art will further understand that virtually any conjunctive word, and / or phrase presenting two or more alternative terms, whether in the specification, claims, or drawings, should be understood to present those possibilities of including one of the terms, either of the terms, or both of the terms. For example, the phrase“A or B” will be understood to include the possibilities of“A,” or“B,” or“A and B.”

[0274] Further, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0275] As those skilled in the art will appreciate, all ranges disclosed herein are also contemplated as individual possibilities for any and all purposes, such as providing written description for example. Any listed range can be easily reduced to at least equal halves, thirds, fourths, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be easily broken down into a lower third, a middle third, and an upper third, etc. All language such as“up to,”“at least,”“greater than,”“less than,” and the like include the recited value and refer to ranges that can be broken down as described above. Finally, as those skilled in the art will appreciate, ranges include each individual member. Thus, for example, a group of 1 to 3 items refers to a group of 1, 2, or 3 items. Similarly, a group of 1 to 5 items refers to a group of 1, 2, 3, 4, or 5 items, etc. While various aspects and implementations have been disclosed herein, other aspects and implementations will be apparent to those skilled in the art. The various aspects and implementations disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

Claims

1. A stress supplement composition comprising: One or more compounds capable of regulating metabolic glutamate receptors; and a carrier.

2. The composition according to claim 1, wherein the one or more compounds are compounds of formula (I) or salts thereof: (I) in, R 1 R 2 R 3 and R 4 Each is independently selected from hydrogen, deuterium, hydroxyl, halogen, ketone, optionally substituted ester, optionally substituted aryl, optionally substituted alkoxy, optionally substituted C1-C6-alkyl, optionally substituted -O-C1-C6-alkyl or optionally substituted C3-C6 cycloalkyl.

3. The composition according to claim 2, wherein R 1 It can be hydrogen or hydroxyl.

4. The composition according to claim 2, wherein R 2 It can be a hydroxyl group or a ketone.

5. The composition according to claim 2, wherein R 3 It can be a hydroxyl group or a ketone.

6. The composition according to claim 2, wherein R4 is hydrogen, hydroxyl, ketone, optionally substituted O-C1-C6-alkyl, or optionally substituted C1-C6-alkyl.

7. The composition according to claim 1, wherein the one or more compounds are selected from: 、 、 、 、 、 、 、 、 、 、 、 、 Or a combination thereof.

8. The composition according to claim 1, wherein the metabolized glutamate receptor is a type II receptor.

9. The composition according to claim 1, wherein one or more compounds are derived from plant extracts.

10. The composition according to claim 9, wherein the plant extract is selected from: rhubarb, amla, apple, tripterygium wilfordii, aloe vera, cocoa, papaya, St. John's wort, Satsuma mandarin orange, lotus, *Acacia*, *Absbreviate*, *Cassia fistula*, *Cola chinensis*, *Eriocaulon buergerianum*, *Eriocaulon buergerianum*, *Macbridei*, *Acaulis*, arnica, carrot, *Bauhinia*, *Botrytis cinerea*, *Acutifolium*, paper mulberry, paper mulberry, *Dalbergia latifolia*, *Dracaena fragrans*, *Dracaena cambodiana*, *Dracaena fragrans*, *Daffodil*, *Guianensis*, *Rohdeachinensis*, Indian rosewood, *Taxus chinensis*, *Tupistra* chinensis), chicken bone grass, Guangzhou acacia, achyranthes, aconite sera, aconite tasiromontanum, rhizome of sweet flag, money flag, sweet flag, Chinese kiwi, Madagascar baobab, giant African cardamom, gray hairy sedge, acacia var. sarcodactylis, Oriental water plantain, fortress aloe, aloe, galangal, millet, white peony, amphorogyne spicata, milky white fragrant green, cow tongue grass, loose flower andrographis paniculata, andrographis paniculata, anemarrhena, denticulatus, Taiwan aralia, artemisia annua, southwestern wormwood, wormwood [synonyms: wormwood, wormwood], heterochromatic white oak, root and rhizome of aster, Aster sedifolius, aster, Atadinus libanoticus, *Potosina*, *Heliotropium indicum*, *Ceratophyllum demersum*, *Cephalotaxus fortunei*, *Polygonum aviculare*, *Polygonum aviculare*, *Rhizoma Ramulus*, *Rhizoma Cynoglossum*, *Rhizoma Cynoglossum* [synonyms: *Rhizoma Cynoglossum*, *Rhizoma Cynoglossum*], *Fritillaria cirrhosa* bulb, *Fritillaria cirrhosa*, *Caulocystis*, *Caulocystis chinensis ... cephalornithos, *Cephalotaxus fortunei*, ...(canarensis), Derris oblonga, Dianthus superbus, Dianthus chinensis, Dictyopteris australis, Gynostemma pentaphyllum, Dioscorea opposita, Dipsacus asperoides, Cyathea spinulosa, Cyathea odorata, Cyathea odorata, Enceliopsis argophylla, Endophytic aspergillus, Epimedium brevicornu, Epimedium brevicornu, Mollis, Eriocaulon buergerianum, Eriocaulon buergerianum, Erythrina variegata, Erythrina variegata, Erythrina variegata, Erythrina variegata, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum ruticarpa), buckwheat, bitter buckwheat, Polygonum multiflorum, Polygonum multiflorum genus Sachalinensis, Yunnan thorny hedge, European buckthorn, Bosch buckthorn, Triplelinervia genus, Gambusa genus, Quadripartita genus, licorice, cudweed, field clover, English ivy, Chionosphaerum genus, Helichrysum genus, Partridge flower, Hovenia dulcis, Lemmonii genus, Hypericum perforatum, Treasure grass, Isatis root, woad, morning glory, juniper, Acanthus genus, Plumieri genus, lettuce, Edelweiss, Japanese larch, lavender, small brown columnar, Lespedeza velutipes, Lilium bulbus, Lilium browniif. e. brown var. colchesteri wils, Lilium brownii var. viridulum (synonyms: wild lily (Lilium brown), lily (Lilium brownii var. viridulum)), *Lobelia* *berlandieri*, *Taxillus chinensis*, *Lupinus*, *Lycium chinense*, *Tinctoria*, *Michelia champaca*, *Magnolia officinalis*, *Gnaphalium affine*, *Cornus trifoliata*, *Mentha haplocalyx*, *Mentha haplocalyx*, *Nigra*, *Angelica pubescens*, *Cercidiphyllum japonicum*, *Tamiflua spp.*, *Tetracentron sinense*, *Cercidiphyllum japonicum*, *Hemiii*, *Nepeta grandiflora*, *Nepeta parvifolia*, *Floribunda*, *Oryctes* Monoceros, Red-stalked Osmanthus, Passionflower (sexflora), Polygonum (decipiens), Water Polygonum, Spring Polygonum, Rumex japonicus, Rumex pubescens, Inflata (subspecies of Petunia purpurea), Common Bean, Flame Flower, Photinia, Ground Cherry, Antidesma, Hirsuta, Teapensis, TeapensisTul., bitterwood, white pea, plantain, long-leaved plantain, single-leaved violet, Yunnan single-leaved violet, silver thread tea genus alternifolium, broad-bracted chrysanthemum genus odora, rare hairy fern genus pennigera, Japanese knotweed rhizome and root, Japanese knotweed, Polygonum hypoleucum, Polygonum multiflorum, *Polygonum cuspidatum*, golden larch, Christmas berry genus glaberrimum, Christmas berry genus laurentii, Christmas berry genus tenuifolium, nine-jointed genus stachyoides, red oak, ramie root, rhubarb, rhubarb (processed), Cuban labe, Japanese knotweed, medicinal buckthorn, buckthorn, buckthorn, buckthorn genus erythroxyloides, Taiwan buckthorn, European buckthorn (Rhamnus frangula) [Synonym: European buckthorn (Frangula)] [alnus], European Rhamnus, Rhamnus hirtella, Rhamnus kurdica, Taichung Rhamnus, Nepalese Rhamnus, Rhamnus pallasii, Holly-like Rhamnus, Creeping Rhamnus, Rhamnus punctata, Rhamnus saxatilis, Rhamnus thymifolius, Rhamnus triquetra, Rhamnus wightii, Heart-leaved Rhamnus, Bract-leaved Rhamnus, Altai Rhamnus, Tibetan Rhamnus, Dense-series Rhamnus, Rhamnus coreanum, Yunnan Rhamnus, Tibetan Rhamnus (Rheum emodi) [Synonym: Tibetan Rhamnus (Rheum emodi)] Rhubarb (Australe), Rhubarb undulatus, Rhubarb hainanense, Rhubarb rubratus, Rhubarb sparseis, Rhubarb lijiangensis, Rhubarb dwarf, Rhubarb tatarica, Rhubarb palmatum, Rhubarb simianum, Rhubarb variegata, Rhubarb reticulateus, Rhubarb undulatus, Rhubarb edible, Rhubarb currantis, Rhubarb tatarica, Rhubarb genus, Rhubarb drooping, Rhubarb sparseis, Rhubarb genus, Rhubarb variegata, Rhubarb scabra, Rhubarb variegata, Rhubarb variegata, Rhubarb variegata, Rhubarb tianshanensis, Rhubarb tianshanensis, Rhubarb yunnanensis, Fagopyrum cymosum, Rhodiola rosea, Rhodiola dahurica, Rhodiola xinanense, Rhodiola dahurica ... Sorrel, Sorrel genus aegyptiacus, Alpine Sorrel, Sorrel genus bequaertii, Reticulate Sorrel, Wrinkled-leaved Sorrel, Sorrel genus cristata, Sorrel genus cyprius, Toothed Sorrel, Sheep's Hoof, Sorrel genus lanceolatus, Sorrel genus limoniastrum, Nepalese Sorrel, Batian Sorrel, Sorrel genus pictus, Sorrel genus pulcher, Sorrel genus ruwenzoriensis, French Sorrel, Sorrel genus simpliciflorus, Sorrel genus (Rumex spp.), Sorrel genus tuberosus, Sorrel genus (usambarensis), Bladder Sorrel, Brown Sage, Cherry Sage, Sargentodoxa cuneata, Sargentodoxaecaulis), three white grass, artemisiifolium, socialis, selaginella, morning glory, behnii, bonariensis, praecox, nearly entire selaginella, senna leaf, angustiiliqua, senna leaf, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, ironwood, senna, senna, senna, orinocensis, bombaiensis, cleistogamum, sophora and rhizome, datura, Sphaerella rosigena, spinach, stevia (Berlandieri), stevia (Ovata), Australian rose apple, lace marigold, red pyrethrum, rubber grass, broad-fruited dandelion subspecies hondoense, Evodia rutaecarpa, yemense (Yemense), coarse-haired daphne, tribulus fruit, tribulus, afzelii, heteropteran, hairy winged drupe, dense-flowered winged drupe, winged drupe, Indian winged drupe, thapsiforme, Vismia guianensis, Vismia guineensis, Vismia laurentii, Vismia orientalis, grape, WilbrandiaBracteata, Xanthium sibiricum, Viscosum, Angelica dahurica, Rhamnus spp., Geranium speckle, Rumex rubrum, Aloe vera, Senna, Aloe arborescens, Aloe vera, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Tenuifolius, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Chaenomeles speciosa, Hissarica, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Cassia fistula, Cassia fistula, Mimosa pudica, Myrrha arborescens, Rhamnus spp., Rhamnus spp., Rhamnus spp., Cassia fistula, Cassia arborescens *Torchella multiflora*, *Insignis*, *Isoetifolia*, *Schimperi*, *Antidesma*, *Hirsute*, Guava, *Polygonum cuspidatum*, *Rhamnus scutellarioides ... Sorrel (Cristatus), Sorrel (Rumex paulsenianus), French Sorrel (Rumex scutatus), Selaginella tamariscina, Senna, Senna long-spike, Senna obtuse-leaved, Senna petersiana, Senna Reticulata, Ironwood, Cassia Seed, Dense Flower Bean, Ding's Golden Vine, Australian Yellow Gum Tree, Chicory, Glory of the Glory Tree, Morinda officinalis, Original Lala Vine, Kalanchoe blossfeldiana, Chrysanthemum indicum, Citrus reticulata, Lemongrass Leaf, South American Weed, Angelica dahurica, Caribbean Grape, Mirabilis jalapa, Coriander, Bauhinia purpurea, Juniperus chinensis, Forsythia, Sweet Orange, Moss, Safflower, Rosemary, Rice, Red Clover, Barley, Pitcher Plant, Small-fruited Musa, Douglas Fir (original variety), Cocoa, Barley, Pitcher Plant, Small-fruited Musa, Douglas Fir (original variety), Valerian Leaf Fennel, Pea, Soybean, Oat, Apple, Gardenia, Cape Aloe, Rice, Small-bean Coffee, Safflower, Hard-skinned Bean, Eggplant, Satsuma Mandarin, St. John's Wort, Turmeric, Water Coconut, Cereale cv.Aroostook, Polygonum tinctorium, Hemp, Tomato, Clementine, Red Clover, Uncaria rhynchophylla, Judas mushroom, Sweet orange, Cycas revoluta, Bitter melon, Dragon bone mustard, Gaillardia fuciformis, Lotus, Black radish, Inca radish, Corn, Tobacco, Ochre mushroom, Flax, Peony, Chili pepper, Tridentaria tridentata, Mirabilis jalapa, Periwinkle, Alfalfa subspecies, Solanum nigrum, Small-bean coffee, Bitter melon, Milk thistle, Cocoa, Cape aloe, Gardenia, Cashew, Chili pepper, Peony, Clementine, Barley, Erucastrum Gallicum, Flax, Syrian Milkweed, Oats, St. John's wort, Turmeric, Corn, Three-toothed Rosewood, Tobacco, Eucalyptus spp., Small-fruited Banana, Eggplant, Phyllanthus emblica, Tomato, Veronica, Hollyhock, Starflower, Jade Tree, Clustered Flower, Lemon, Periwinkle, Mirabilis jalapa, Podocarpus spp., Tripterygium wilfordii, Dense Flower Bean, Crinum asiaticum, Juniperus chinensis, Pleurotus ostreatus, Obtuse Leaf Stone Flower, False Wampee, Gynostemma pentaphyllum, Red Clover, Rice, Rosemary, Lotus, Safflower, Satsuma mandarin orange, Moss, Sweet orange, Juniperus chinensis 'Pleurotus's purpurea', Forsythia suspensa, Bitter melon, Milk thistle, Cape aloe, Clementine mandarin orange, Barley, Erucastrum Gallicum, Flax, Syrian Milkweed, St. John's Wort, Three-toothed Rosemary, Eucalyptus, Phyllanthus, Veronica, Althaea, Rosehip, Periwinkle, Podocarpus, Tripterygium wilfordii, Juniperus chinensis, Pleurotus ostreatus, Lithospermum obtuseum, Phellodendron amurense, Chrysanthemum indicum, Trifolium repens, Rosemary, Lotus, Satsuma mandarin orange, Moss, Sweet orange, Juniperus chinensis, Forsythia or combinations thereof.

11. The composition according to claim 10, wherein the plant extract is selected from rhubarb, cocoa, barley, papaya, pitcher plant (Nepenthes hoebe), small-fruited banana, Douglas fir (original variety), Valerian leaf pine (Vallisneria natans), pea, African aloe, soybean, oat, apple, gardenia, Cape aloe, rice, small-grain coffee, safflower, hard-skinned bean, eggplant, aloe, Wenzhou mandarin orange, St. John's wort, turmeric, water coconut, Cereale cv. Aroostook, Polygonum tinctorium, hemp, tomato, Clementine red mandarin orange, red clover, Uncaria rhynchophylla, Judas aurantium, sweet orange, cycad, bitter melon, dragon bone mustard, Gaillardia elegans, lotus, black radish, Inca radish, corn, tobacco, ochre mushroom, flax, peony, chili pepper, three-toothed sage, four o'clock flower, periwinkle, or combinations thereof.

12. The composition according to claim 10, wherein the plant extract is selected from rhubarb, amla, cocoa, or a combination thereof.

13. The composition according to claim 10, wherein the plant extract is selected from Tripterygium wilfordii, Phyllanthus emblica, St. John's wort, Aloe vera, St. John's wort or a combination thereof.

14. The composition of claim 10, wherein the one or more compounds from the plant extract are selected from: 、 、 、 、 、 、 、 、 、 、 , or 。 15. The composition according to claim 1, wherein the composition is formulated as a dietary supplement, food ingredient or additive, medical food, nutritional composition or pharmaceutical composition.

16. The composition of claim 1, wherein the dosage form of the composition is configured as one of soft capsules, hard capsules, gummies, functional beverages, functional foods, liquids, powders, and tablets.

17. The composition of claim 10, wherein the composition comprises 1.0% to 99% w / w of the plant extract.

18. The composition of claim 1, wherein the composition further comprises a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof.

19. The composition according to claim 7, wherein one or more compounds are 。 20. The composition according to claim 7, wherein one or more compounds are 。 21. The composition according to claim 7, wherein one or more compounds are 。 22. A method for treating, reducing, preventing, or alleviating stress, stress symptoms, or the harmful effects of chronic stress in a subject, said method comprising: A composition is provided to the object, the composition comprising one or more compounds and a carrier capable of modulating metabolic glutamate receptors. The composition is provided in an amount sufficient to treat, reduce, prevent or alleviate stress, stress symptoms or the harmful effects of stress.

23. The method according to claim 22, wherein the one or more compounds are compounds of formula (I) or salts thereof: (I) in, R 1 R 2 R 3 and R 4 Each is independently selected from hydrogen, deuterium, hydroxyl, halogen, ketone, optionally substituted ester, optionally substituted aryl, optionally substituted alkoxy, optionally substituted C1-C6-alkyl, optionally substituted -O-C1-C6-alkyl or optionally substituted C3-C6 cycloalkyl.

24. The method of claim 23, wherein R 1 It can be hydrogen or hydroxyl.

25. The method of claim 23, wherein R 2 It can be a hydroxyl group or a ketone.

26. The method of claim 23, wherein R 3 It can be a hydroxyl group or a ketone.

27. The method of claim 23, wherein R4 is hydrogen, hydroxyl, ketone, optionally substituted O-C1-C6-alkyl, or optionally substituted C1-C6-alkyl.

28. The method of claim 22, wherein the compound is selected from: 、 、 、 、 、 、 、 、 、 、 , or 。 29. The method of claim 22, wherein the composition is provided to maintain the healthy stress response of the subject.

30. The method of claim 22, wherein the composition is provided to maintain glutamate homeostasis of the object.

31. The method of claim 22, wherein the composition is provided to modulate the stress of the object.

32. The method of claim 22, wherein the composition is provided to provide emotional support to the subject.

33. The method of claim 30, wherein the compound is an mGlu2 agonist and a positive allosteric modulator, or an mGlu3 agonist and a positive allosteric modulator.

34. The method of claim 30, wherein the compound is an mGlu2 antagonist and a negative allosteric modifier, or an mGlu3 antagonist and a negative allosteric modifier.

35. The method of claim 22, wherein one or more compounds are derived from plant extracts.

36. The method according to claim 35, wherein the plant extract is selected from: rhubarb, amla, apple, tripterygium wilfordii, aloe vera, cocoa, papaya, St. John's wort, Satsuma mandarin orange, lotus, *Acacia*, *Acacia spp.*, *Cassia fistula*, *Cassia fistula*, *Cola spp.*, *Acacia spp.*, *Macbridei*, *Acacia spp.*, arnica, carrot, *Bauhinia*, *Botrytis cinerea*, *Acutifolium*, paper mulberry, paper mulberry, *Dalbergia latifolia*, *Dracaena fragrans*, *Dracaena fragrans*, *Daffodil*, *Guianensis*, *Rohdeachinensis*, Indian rosewood, *Taxus chinensis*, *Tupistra* chinensis), chicken bone grass, Guangzhou acacia, achyranthes, aconite sera, aconite tasiromontanum, rhizome of sweet flag, money flag, sweet flag, Chinese kiwi, Madagascar baobab, giant African cardamom, gray hairy sedge, acacia var. sarcodactylis, Oriental water plantain, fortress aloe, aloe, galangal, millet, white peony, amphorogyne spicata, milky white fragrant green, cow tongue grass, loose flower andrographis paniculata, andrographis paniculata, anemarrhena, denticulatus, Taiwan aralia, artemisia annua, southwestern wormwood, wormwood [synonyms: wormwood, wormwood], heterochromatic white oak, root and rhizome of aster, Aster sedifolius, aster, Atadinus libanoticus, *Potosina*, *Heliotropium indicum*, *Ceratophyllum demersum*, *Cephalotaxus fortunei*, *Polygonum aviculare*, *Polygonum aviculare*, *Rhizoma Ramulus*, *Rhizoma Cynoglossum*, *Rhizoma Cynoglossum* [synonyms: *Rhizoma Cynoglossum*, *Rhizoma Cynoglossum*], *Fritillaria cirrhosa* bulb, *Fritillaria cirrhosa*, *Caulocystis*, *Caulocystis chinensis ... cephalornithos, *Cephalotaxus fortunei*, ...(canarensis), Derris oblonga, Dianthus superbus, Dianthus chinensis, Dictyopteris australis, Gynostemma pentaphyllum, Dioscorea opposita, Dipsacus asperoides, Cyathea spinulosa, Cyathea odorata, Cyathea odorata, Enceliopsis argophylla, Endophytic aspergillus, Epimedium brevicornu, Epimedium brevicornu, Mollis, Eriocaulon buergerianum, Eriocaulon buergerianum, Erythrina variegata, Erythrina variegata, Erythrina variegata, Erythrina variegata, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum, Eriocaulon buergerianum ruticarpa), buckwheat, bitter buckwheat, Polygonum multiflorum, Polygonum multiflorum genus Sachalinensis, Yunnan thorny hedge, European buckthorn, Bosch buckthorn, Triplelinervia genus, Gambusa genus, Quadripartita genus, licorice, cudweed, field clover, English ivy, Chionosphaerum genus, Helichrysum genus, Partridge flower, Hovenia dulcis, Lemmonii genus, Hypericum perforatum, Treasure grass, Isatis root, woad, morning glory, juniper, Acanthus genus, Plumieri genus, lettuce, Edelweiss, Japanese larch, lavender, small brown columnar, Lespedeza velutipes, Lilium bulbus, Lilium browniif. e. brown var. colchesteri wils, Lilium brownii var. viridulum (synonyms: wild lily (Lilium brown), lily (Lilium brownii var. viridulum)), *Lobelia* *berlandieri*, *Taxillus chinensis*, *Lupinus*, *Lycium chinense*, *Tinctoria*, *Michelia champaca*, *Magnolia officinalis*, *Gnaphalium affine*, *Cornus trifoliata*, *Mentha haplocalyx*, *Mentha haplocalyx*, *Nigra*, *Angelica pubescens*, *Cercidiphyllum japonicum*, *Tamiflua spp.*, *Tetracentron sinense*, *Cercidiphyllum japonicum*, *Hemiii*, *Nepeta grandiflora*, *Nepeta parvifolia*, *Floribunda*, *Oryctes* Monoceros, Red-stalked Osmanthus, Passionflower (sexflora), Polygonum (decipiens), Water Polygonum, Spring Polygonum, Rumex japonicus, Rumex pubescens, Inflata (subspecies of Petunia purpurea), Common Bean, Flame Flower, Photinia, Ground Cherry, Antidesma, Hirsuta, Teapensis, TeapensisTul., bitterwood, white pea, plantain, long-leaved plantain, single-leaved violet, Yunnan single-leaved violet, silver thread tea genus alternifolium, broad-bracted chrysanthemum genus odora, rare hairy fern genus pennigera, Japanese knotweed rhizome and root, Japanese knotweed, Polygonum hypoleucum, Polygonum multiflorum, *Polygonum cuspidatum*, golden larch, Christmas berry genus glaberrimum, Christmas berry genus laurentii, Christmas berry genus tenuifolium, nine-jointed genus stachyoides, red oak, ramie root, rhubarb, rhubarb (processed), Cuban labe, Japanese knotweed, medicinal buckthorn, buckthorn, buckthorn, buckthorn genus erythroxyloides, Taiwan buckthorn, European buckthorn (Rhamnus frangula) [Synonym: European buckthorn (Frangula)] [alnus], European Rhamnus, Rhamnus hirtella, Rhamnus kurdica, Taichung Rhamnus, Nepalese Rhamnus, Rhamnus pallasii, Holly-like Rhamnus, Creeping Rhamnus, Rhamnus punctata, Rhamnus saxatilis, Rhamnus thymifolius, Rhamnus triquetra, Rhamnus wightii, Heart-leaved Rhamnus, Bract-leaved Rhamnus, Altai Rhamnus, Tibetan Rhamnus, Dense-series Rhamnus, Rhamnus coreanum, Yunnan Rhamnus, Tibetan Rhamnus (Rheum emodi) [Synonym: Tibetan Rhamnus (Rheum emodi)] Rhubarb (Australe), Rhubarb undulatus, Rhubarb hainanense, Rhubarb rubratus, Rhubarb sparseis, Rhubarb lijiangensis, Rhubarb dwarf, Rhubarb tatarica, Rhubarb palmatum, Rhubarb simianum, Rhubarb variegata, Rhubarb reticulateus, Rhubarb undulatus, Rhubarb edible, Rhubarb currantis, Rhubarb tatarica, Rhubarb genus, Rhubarb drooping, Rhubarb sparseis, Rhubarb genus, Rhubarb variegata, Rhubarb scabra, Rhubarb variegata, Rhubarb variegata, Rhubarb variegata, Rhubarb tianshanensis, Rhubarb tianshanensis, Rhubarb yunnanensis, Fagopyrum cymosum, Rhodiola rosea, Rhodiola dahurica, Rhodiola xinanense, Rhodiola dahurica ... Sorrel, Sorrel genus aegyptiacus, Alpine Sorrel, Sorrel genus bequaertii, Reticulate Sorrel, Wrinkled-leaved Sorrel, Sorrel genus cristata, Sorrel genus cyprius, Toothed Sorrel, Sheep's Hoof, Sorrel genus lanceolatus, Sorrel genus limoniastrum, Nepalese Sorrel, Batian Sorrel, Sorrel genus pictus, Sorrel genus pulcher, Sorrel genus ruwenzoriensis, French Sorrel, Sorrel genus simpliciflorus, Sorrel genus (Rumex spp.), Sorrel genus tuberosus, Sorrel genus (usambarensis), Bladder Sorrel, Brown Sage, Cherry Sage, Sargentodoxa cuneata, Sargentodoxaecaulis), three white grass, artemisiifolium, socialis, selaginella, morning glory, behnii, bonariensis, praecox, nearly entire selaginella, senna leaf, angustiiliqua, senna leaf, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, senna, ironwood, senna, senna, senna, orinocensis, bombaiensis, cleistogamum, sophora and rhizome, datura, Sphaerella rosigena, spinach, stevia (Berlandieri), stevia (Ovata), Australian rose apple, lace marigold, red pyrethrum, rubber grass, broad-fruited dandelion subspecies hondoense, Evodia rutaecarpa, yemense (Yemense), coarse-haired daphne, tribulus fruit, tribulus, afzelii, heteropteran, hairy winged drupe, dense-flowered winged drupe, winged drupe, Indian winged drupe, thapsiforme, Vismia guianensis, Vismia guineensis, Vismia laurentii, Vismia orientalis, grape, WilbrandiaBracteata, Xanthium sibiricum, Viscosum, Angelica dahurica, Rhamnus spp., Geranium speckle, Rumex rubrum, Aloe vera, Senna, Aloe arborescens, Aloe vera, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Tenuifolius, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Chaenomeles speciosa, Hissarica, Aloe arborescens, Aloe arborescens, Aloe arborescens, Aloe arborescens, Cassia fistula, Cassia fistula, Mimosa pudica, Myrrha arborescens, Rhamnus spp., Rhamnus spp., Rhamnus spp., Cassia fistula, Cassia arborescens *Torchella multiflora*, *Insignis*, *Isoetifolia*, *Schimperi*, *Antidesma*, *Hirsute*, Guava, *Polygonum cuspidatum*, *Rhamnus scutellarioides ... Sorrel (Cristatus), Sorrel (Rumex paulsenianus), French Sorrel (Rumex scutatus), Selaginella tamariscina, Senna, Senna long-spike, Senna obtuse-leaved, Senna petersiana, Senna Reticulata, Ironwood, Cassia Seed, Dense Flower Bean, Ding's Golden Vine, Australian Yellow Gum Tree, Chicory, Glory of the Glory Tree, Morinda officinalis, Original Lala Vine, Kalanchoe blossfeldiana, Chrysanthemum indicum, Citrus reticulata, Lemongrass Leaf, South American Weed, Angelica dahurica, Caribbean Grape, Mirabilis jalapa, Coriander, Bauhinia purpurea, Juniperus chinensis, Forsythia, Sweet Orange, Moss, Safflower, Rosemary, Rice, Red Clover, Barley, Pitcher Plant, Small-fruited Musa, Douglas Fir (original variety), Cocoa, Barley, Pitcher Plant, Small-fruited Musa, Douglas Fir (original variety), Valerian Leaf Fennel, Pea, Soybean, Oat, Apple, Gardenia, Cape Aloe, Rice, Small-bean Coffee, Safflower, Hard-skinned Bean, Eggplant, Satsuma Mandarin, St. John's Wort, Turmeric, Water Coconut, Cereale cv.Aroostook, Polygonum tinctorium, Hemp, Tomato, Clementine, Red Clover, Uncaria rhynchophylla, Judas mushroom, Sweet orange, Cycas revoluta, Bitter melon, Dragon bone mustard, Gaillardia fuciformis, Lotus, Black radish, Inca radish, Corn, Tobacco, Ochre mushroom, Flax, Peony, Chili pepper, Tridentaria tridentata, Mirabilis jalapa, Periwinkle, Alfalfa subspecies, Solanum nigrum, Small-bean coffee, Bitter melon, Milk thistle, Cocoa, Cape aloe, Gardenia, Cashew, Chili pepper, Peony, Clementine, Barley, Erucastrum Gallicum, Flax, Syrian Milkweed, Oats, St. John's wort, Turmeric, Corn, Three-toothed Rosewood, Tobacco, Eucalyptus spp., Small-fruited Banana, Eggplant, Phyllanthus emblica, Tomato, Veronica, Hollyhock, Starflower, Jade Tree, Clustered Flower, Lemon, Periwinkle, Mirabilis jalapa, Podocarpus spp., Tripterygium wilfordii, Dense Flower Bean, Crinum asiaticum, Juniperus chinensis, Pleurotus ostreatus, Obtuse Leaf Stone Flower, False Wampee, Gynostemma pentaphyllum, Red Clover, Rice, Rosemary, Lotus, Safflower, Satsuma mandarin orange, Moss, Sweet orange, Juniperus chinensis 'Pleurotus's purpurea', Forsythia suspensa, Bitter melon, Milk thistle, Cape aloe, Clementine mandarin orange, Barley, Erucastrum Gallicum, Flax, Syrian Milkweed, St. John's Wort, Three-toothed Rosemary, Eucalyptus, Phyllanthus, Veronica, Althaea, Rosehip, Periwinkle, Podocarpus, Tripterygium wilfordii, Juniperus chinensis, Pleurotus ostreatus, Lithospermum obtuseum, Phellodendron amurense, Chrysanthemum indicum, Trifolium repens, Rosemary, Lotus, Satsuma mandarin orange, Moss, Sweet orange, Juniperus chinensis, Forsythia or combinations thereof.

37. The method according to claim 35, wherein the plant extract is selected from rhubarb, cocoa, barley, papaya, pitcher plant, small-fruited banana, Douglas fir (original variety), valerian leaf euphorbia, pea, African aloe, soybean, oat, apple, gardenia, Cape aloe, rice, small-grain coffee, safflower, hard-skinned bean, eggplant, aloe, Wenzhou mandarin orange, St. John's wort, turmeric, water coconut, ryegrass cv. Aroostook, indigo, hemp, tomato, cremandin, red clover, Uncaria rhynchophylla, Judas aurantium, sweet orange, cycad, bitter melon, dragon bone mustard, Gaillardia elegans, lotus, black radish, Inca radish, corn, tobacco, ochre mushroom, flax, peony, chili pepper, three-toothed sage, four o'clock flower, periwinkle, or combinations thereof.

38. The method according to claim 35, wherein the plant extract is selected from rhubarb, amla, cocoa, or a combination thereof.

39. The method according to claim 35, wherein the plant extract is selected from Tripterygium wilfordii, Phyllanthus emblica, St. John's wort, Aloe vera, St. John's wort or a combination thereof.

40. The method of claim 35, wherein the one or more compounds from the plant extract are selected from: 、 、 、 、 、 、 、 、 、 、 , or 。 41. The method of claim 22, wherein the composition is formulated as a dietary supplement, food ingredient or additive, medical food, nutritional composition or pharmaceutical composition.

42. The method of claim 22, wherein the dosage form of the composition is configured as one of soft capsules, hard capsules, gummies, functional beverages, functional foods, liquids, powders, and tablets.

43. The method of claim 35, wherein the composition comprises 1.0% to 99% w / w of the plant extract.

44. The method of claim 22, wherein the composition further comprises a preservative, a sweetener, a colorant, an additive, a flavoring agent, or a combination thereof.

45. A method for treating, preventing, reducing, regulating, or alleviating anxiety in a subject, the method comprising: A composition is provided to the object, the composition comprising one or more compounds and a carrier capable of modulating metabolic glutamate receptors. The composition is provided in an amount sufficient to treat, reduce, prevent or alleviate the anxiety of the subject; The one or more compounds mentioned above are selected from: 、 、 、 、 、 、 、 、 、 、 、 、 Or a combination thereof.

46. ​​A method for treating, preventing, reducing, regulating, or alleviating the negative effects of emotional stress on a subject's sleep, the method comprising: A composition is provided to the object, the composition comprising one or more compounds and a carrier capable of modulating metabolic glutamate receptors. The composition is provided in an amount sufficient to treat, reduce, prevent or alleviate the anxiety of the subject; The one or more compounds mentioned above are selected from: 、 、 、 、 、 、 、 、 、 、 、 、 Or a combination thereof.

47. A method for treating, preventing, reducing, regulating, or alleviating the negative effects of a subject's physiological rhythms, the method comprising: A composition is provided to the object, the composition comprising one or more compounds and a carrier capable of modulating metabolic glutamate receptors. The composition is provided in an amount sufficient to treat, reduce, prevent or alleviate the anxiety of the subject; The one or more compounds mentioned above are selected from: 、 、 、 、 、 、 、 、 、 、 , or Or a combination thereof.

48. A method for treating, preventing, reducing, regulating, or alleviating negative emotional impacts on a subject, the method comprising: A composition is provided to the object, the composition comprising one or more compounds and a carrier capable of modulating metabolic glutamate receptors. The composition is provided in an amount sufficient to treat, reduce, prevent or alleviate the anxiety of the subject; The one or more compounds mentioned above are selected from: 、 、 、 、 、 、 、 、 、 、 , or Or a combination thereof.

49. An oral composition for a medicament intended to treat stress, anxiety, insomnia, or related conditions, said oral composition comprising compounds selected from: 、 、 、 、 、 、 、 、 、 、 , or Or a combination thereof.

50. Use of a composition for treating, reducing, preventing, or alleviating stress, stress symptoms, or the harmful effects of chronic stress in a subject, wherein the composition comprises one or more compounds selected from the group consisting of: 、 、 、 、 、 、 、 、 、 、 , or Or a combination thereof.

Images