Composition for improving barrier function of intestinal tract

Abstract

The present invention provides a composition for improving the barrier function of the intestinal tract. The invention relates to a composition for improving the barrier function of the intestinal tract. The traditional Chinese medicine composition is prepared from urtica heterophyllus, purple perilla, dandelion, golden camellia, codonopsis pilosula, sophora japonica, cistanche, radix angelicae, radix puerariae, ginseng, roselle, tea, chrysanthemum, yam, sea-buckthorn, sambucus nigra, olive, lycium ruthenicum, chenopodium quinoa, radish, grifola frondosa, tartary buckwheat and coprinus comatus. And at least one compound selected from the group consisting of blackberry and raspberry and / or at least one compound selected from the group consisting of phenethyl isothiocyanate and thymoquinone.

Description

Technical Field

[0001] The present invention relates to a composition for improving the barrier function of the intestine. Background Art

[0002] The digestive tract such as the intestine not only absorbs essential nutrients from food, but is also important from the viewpoint of a barrier that separates the outside world from the living body to defend against the invasion of foreign substances such as allergens. If the barrier of the intestine is impaired, harmful substances that should originally be excreted are absorbed from the intestine, causing various adverse effects. Such a disorder of the intestinal barrier is also called intestinal leakage and may be related to various diseases such as food allergy, immune disease, inflammatory bowel disease, irritable bowel syndrome, infectious disease, obesity, diabetes, NAFLD (non-alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), metabolic syndrome, cognitive decline, and depression. Further, a disorder of the barrier function of the intestine may also be related to various skin diseases. For example, it has been reported that for pediatric atopic dermatitis patients, the severity of symptoms is related to intestinal permeability, and psoriasis patients have higher intestinal permeability than healthy people (Patent Documents 1 to 6, Non-Patent Documents 1 to 9).

[0003] In recent years, in order to maintain the health of the whole body and skin, treat and prevent diseases, and achieve cosmetic effects by improving the intestinal barrier function and making the intestinal state good, it has been proposed to ingest prebiotics such as oligosaccharides and probiotics such as lactic acid bacteria in order to improve the intestinal barrier function. In addition, for example, it has been disclosed that an extract of Paeonia suffruticosa Andr. var. spontanea Rehd. has an effect of improving the intestinal barrier function (Patent Document 1). It has also been reported that polyphenols such as compounds having gallic acid residues, flavan-3-ol polymers, nobiletin, kaempferol, quercetin, and myricetin (Patent Documents 2 to 4, Non-Patent Documents 1 to 3) and unsaturated fatty acid metabolites (Patent Document 5) have an effect of improving the intestinal barrier function, and tangeretin has a colitis alleviating effect (Non-Patent Document 4). It has also been reported that proline, serine, and threonine have an effect of healing the intestinal mucosa (Patent Document 6); D-alanine, L-glutamine, glutamine, and whey protein have an effect of improving the intestinal barrier function (Non-Patent Documents 5 to 7). On the other hand, there is currently a need for further substances having a high effect of improving the intestinal barrier function.

[0004] Prior Art Documents

[0005] Patent Documents

[0006] Patent Document 1: Japanese Patent Application Laid-Open No. 2018-140946

[0007] Patent Document 2: International Publication No. 2019 / 131772

[0008] Patent Document 3: International Publication No. 2019 / 131767

[0009] Patent Document 4: International Publication No. WO 2019 / 131759

[0010] Patent Document 5: International Publication No. WO 2014 / 129384

[0011] Patent Document 6: International Publication No. WO 2016 / 116585

[0012] Non-Patent Documents

[0013] Non-Patent Document 1: Xiong Y.et.al., Mol Nutr Food Res. 2015 May; 59(5):829-42 Non-Patent Document 2: Suzuki, T.et.al., J.Nutr. 2011, 141, 87-94

[0014] Non-Patent Document 3: Suzuki, T.et.al., J.Nutr. 2009, 139, 965-74

[0015] Non-Patent Document 4: Su-Hyeon Eun et.al., Planta Med 2017; 83:527-533

[0016] Non-Patent Document 5: Miyauchi, E.et.al., Biosci.Biotechnol.Biochem., 76(2), 283-288, 2012

[0017] Non-Patent Document 6: Jaya Benjamin et.al., Digestive Diseases and Sciences 57(4):1000-12·2012

[0018] Non-Patent Document 7: R.K.Rao et.al., J Epithel Biol Pharmacol. 2012 January; 5(Suppl 1-M7):47-54

[0019] Non-Patent Document 8: Al-Sadi, R.et.al., Am.J.Physiol.Gastrointest.Liver Physiol. 2011, 300, G1054-64

[0020] Non-Patent Document 9: Donato, K.A.et.al., Microbiology 2010, 156, 3288-97 Summary of the Invention

[0021] The present invention provides a composition for improving the barrier function of the intestine.

[0022] The inventors of the present invention surprisingly found that a composition containing specific components can improve the barrier function of the intestine. The present invention is based on these insights.

[0023] According to the present invention, the following inventions are provided.

[0024] (1) A composition for improving the barrier function of the intestine, which comprises one or more selected from the group consisting of Urtica dioica, Perilla frutescens, Taraxacum mongolicum, Camellia nitidissima, Codonopsis pilosula, Sophora japonica, Cistanche deserticola, Angelica dahurica, Pueraria lobata, Panax ginseng, Hibiscus sabdariffa, Camellia sinensis, Chrysanthemum morifolium, Dioscorea opposita, Hippohae rhamnoides, Sambucus nigra, Olea europaea, Lycium ruthenicum, Chenopodium quinoa, Raphanus sativus, Grifola frondosa, Fagopyrum tataricum, Coprinus comatus, Rubus fruticosus, and Rubus idaeus, and / or comprises one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol quinone.

[0025] (2) The composition according to (1), which comprises one or more selected from the group consisting of Urtica dioica, Camellia nitidissima, and Coprinus comatus.

[0026] (3) The composition according to (1) or (2), which is used for strengthening tight junctions.

[0027] (4) The composition according to any one of (1) to (3), which is a food composition.

[0028] According to the present invention, a composition for improving the barrier function of the intestine is provided. In addition, the composition of the present invention can also be used for improving the barrier function of the intestine. Detailed implementation modes

[0029] According to one aspect of the present invention, a composition for improving the barrier function of the intestine is provided. Such a composition comprises one or more selected from the group consisting of Perilla frutescens, Taraxacum mongolicum, Camellia nitidissima, Codonopsis pilosula, Sophora japonica, Cistanche deserticola, Angelica dahurica, Pueraria lobata, Panax ginseng, Hibiscus sabdariffa, Camellia sinensis, Chrysanthemum morifolium, Dioscorea opposita, Hippohae rhamnoides, Sambucus nigra, Olea europaea, Lycium ruthenicum, Chenopodium quinoa, Raphanus sativus, Grifola frondosa, Fagopyrum tataricum, Coprinus comatus, Rubus fruticosus, Urtica dioica, and Rubus idaeus, and / or comprises one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol quinone. Preferably, it comprises one or more selected from the group consisting of Perilla frutescens, Taraxacum mongolicum, Camellia nitidissima, Codonopsis pilosula, Sophora japonica, Cistanche deserticola, Angelica dahurica, Pueraria lobata, Camellia sinensis, Chrysanthemum morifolium, Hippohae rhamnoides, Sambucus nigra, Olea europaea, Lycium ruthenicum, Chenopodium quinoa, Raphanus sativus, Grifola frondosa, Fagopyrum tataricum, Coprinus comatus, Rubus fruticosus, Urtica dioica, and Rubus idaeus, and / or comprises one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol quinone. More preferably, it comprises one or more selected from the group consisting of Camellia nitidissima, Cistanche deserticola, Chrysanthemum morifolium, Sambucus nigra, Olea europaea, Coprinus comatus, and Urtica dioica. Even more preferably, it comprises one or more selected from the group consisting of Camellia nitidissima, Coprinus comatus, and Urtica dioica.

[0030] By applying the above-described composition to an object, the barrier function of the intestine of the object can be improved. Improvement of the barrier function of the intestine is useful for the treatment and / or prevention of various diseases and disorders caused by intestinal barrier dysfunction such as colitis, Crohn's disease and other intestinal diseases, immune diseases such as celiac disease, obesity, diabetes, NAFLD, NASH, metabolic syndrome, allergic diseases, cognitive decline, depression, etc., and for beauty such as improvement of skin condition.

[0031] The barrier function of the intestine in the present invention refers to the function of intestinal epithelial cells that separate the outside from the living body to restrict the invasion of foreign substances and harmful substances such as allergens. For example, there is a structure called tight junction (TJ) at the cell gaps of intestinal epithelial cells, which helps to maintain the barrier function of the intestine by controlling the permeation of substances between cells. In addition, it has been reported that sugars and intestinal flora are also related to the barrier function of the intestine. When the barrier function of the intestine is impaired, unwanted substances permeate through the intestine, which may cause adverse effects such as inflammation in the body (Patent Document 1, Non-Patent Documents 2, 3, 7-9).

[0032] The improvement of the barrier function of the intestine in the present invention may include: preventing and / or treating the disorders of the barrier function of the intestine as described above, maintaining the intestine in a normal state, forming tight junctions / repairing tight junctions / regulating tight junction function, protecting the intestinal mucosa, promoting the formation of mucus layer, etc.

[0033] According to a preferred embodiment of the present invention, there is provided a composition for strengthening tight junctions, such a composition contains one or more selected from the group consisting of perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, ginseng, hibiscus sabdariffa, tea, chrysanthemum, dioscorea opposita, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, urtica dioica and raspberry, and / or contains one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol, preferably contains one or more selected from the group consisting of perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, tea, chrysanthemum, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, urtica dioica and raspberry, and / or contains one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol, more preferably contains one or more selected from the group consisting of camellia nitidissima, cistanche deserticola, chrysanthemum, elderberry, olive, coprinus comatus and urtica dioica, and even more preferably contains one or more selected from the group consisting of camellia nitidissima, coprinus comatus and urtica dioica.

[0034] Strengthening tight junctions in the present invention means changing tight junctions in such a way that the permeation of substances between cells becomes difficult, which can be achieved by, for example, forming tight junctions / repairing tight junctions / regulating tight junction function, etc.

[0035] The improvement of the intestinal barrier function in the present invention can be achieved by strengthening tight junctions, or can be achieved without strengthening tight junctions.

[0036] It is generally known that the intestinal barrier function can be evaluated by various methods. It has been reported that, for example, it can be evaluated by measuring the concentration of lactulose and mannitol in urine after ingestion of the intestinal permeability marker - mannitol (M) and the poorly permeable marker - lactulose (L), and comparing the lactulose / mannitol (L / M) ratio. The L / M ratio 2.5 to 4 hours after ingestion reflects the barrier function of the small intestine (Patent Document 1). In addition, a method for measuring the intestinal barrier function by measuring the transepithelial electric resistance (TER) value between Caco-2 cells of the digestive tract epithelium has also been reported (Patent Document 1, Non-Patent Documents 2, 3, 8, 9). The intestinal barrier function in the present invention can be evaluated by known methods, and is preferably evaluated based on the measured value of the transepithelial electric resistance (TER) between Caco-2 cells.

[0037] The composition of the present invention can be used in either in vivo or in vitro. The composition of the present invention is preferably used for human cells, but is of course not limited thereto.

[0038] The "perilla" in the present invention refers to perilla as a plant species of the genus Perilla in the family Lamiaceae, including, for example, those denoted as Perilla frutescens (L.) Britt. As the part to be used, there is of course no limitation, and the whole plant or leaves are preferred. The "perilla" in the present invention can be used as it is or after being processed such as dried according to needs. When these are commercially available, as long as commercially available products having the target effects of the present invention can be obtained, the commercially available products can also be used.

[0039] The "dandelion" in the present invention refers to dandelion as a plant species of the genus Taraxacum in the family Asteraceae, including, for example, those denoted as Taraxacum mongolicum Hand.-Mazz, Taraxacum borealisinense Kitam. As the part to be used, there is of course no limitation, and the whole plant is preferred. The "dandelion" in the present invention can be used as it is or after being processed such as dried according to needs. When these are commercially available, as long as commercially available products having the target effects of the present invention can be obtained, the commercially available products can also be used.

[0040] The "Camellia chrysantha" of the present invention refers to Camellia chrysantha belonging to the plant genus Camellia of the family Theaceae, including, for example, those denoted as Camellia chrysantha (Hu) Tuyama. As the part to be used, there is of course no limitation, and leaves are preferred. The "Camellia chrysantha" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0041] The "Codonopsis pilosula" of the present invention refers to Codonopsis pilosula belonging to the plant genus Codonopsis of the family Campanulaceae, also denoted as Codonopsis pilosula (Franch.). As the part to be used, there is of course no limitation, and roots are preferred. The "Codonopsis pilosula" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0042] The "Sophora japonica" of the present invention refers to Sophora japonica belonging to the plant genus Sophora of the family Fabaceae, also denoted as Sophora japonica L. As the part to be used, there is of course no limitation, and flowers or flower buds are preferred. The "Sophora japonica" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0043] The "Cistanche deserticola" of the present invention refers to the parasitic plant Cistanche deserticola collected from arid regions in the western part of Inner Mongolia, China, etc., also denoted as Cistanche deserticola Y.C.Ma. As the part to be used, there is of course no limitation, and fleshy stems are preferred. The "Cistanche deserticola" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0044] The "Angelica dahurica" of the present invention refers to Angelica dahurica belonging to the plant genus Angelica of the family Apiaceae, including those also denoted as Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. As the part to be used, there is of course no limitation, and roots are preferred. The "Angelica dahurica" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0045] "Ge" in the present invention refers to Ge of the plant genus Pueraria in the legume family, including those also denoted as Pueraria lobata (Willd.) Ohwi. As the used part, there is of course no limitation, and the root is preferred. "Ge" in the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0046] "Ginseng" in the present invention refers to ginseng (Korean ginseng) of the plant genus Panax in the Araliaceae family, also denoted as Panax ginseng C.A.Mey. As the used part, there is of course no limitation, and the root is preferred. "Ginseng" in the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0047] "Roselle" in the present invention refers to roselle of the plant genus Hibiscus in the Malvaceae family, including those also denoted as Hibiscus sabdariffa Linn. As the used part, there is of course no limitation, and the calyx or fruit is preferred. "Roselle" in the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0048] "Tea" in the present invention refers to tea of the plant genus Camellia in the Theaceae family, also denoted as Camellia sinensis. As the used part, there is of course no limitation, and the leaf is preferred. "Tea" in the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0049] "Chrysanthemum" in the present invention refers to chrysanthemum of the plant genus Chrysanthemum in the Asteraceae family, including those also denoted as Chrysanthemum morifolium Ramat. As the used part, there is of course no limitation, and the flower is preferred. "Chrysanthemum" in the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0050] "Yam" in the present invention refers to yam of the plant genus Dioscorea in the Dioscoreaceae family, including those also denoted as Dioscorea opposita Thunb. As the used part, there is of course no limitation, and the rhizome is preferred. "Yam" in the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0051] The "seabuckthorn" of the present invention refers to the seabuckthorn of the plant genus Hippophae in the Elaeagnaceae family, also denoted as Hippophae rhamnoides L. As the part to be used, there is of course no limitation, and the fruit is preferably used. The "seabuckthorn" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0052] The "elderberry" of the present invention refers to the elderberry of the plant genus Sambucus in the Caprifoliaceae family, also denoted as Sambucus nigra L. As the part to be used, there is of course no limitation, and the fruit (pulp, pericarp, etc.) is preferably used. The "elderberry" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0053] The "olive" of the present invention refers to the olive of the plant genus Canarium in the Burseraceae family, including those also denoted as Canarium album Raeusch. As the part to be used, there is of course no limitation, and the fruit (pulp, pericarp, etc.) is preferably used. The "olive" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0054] The "black goji berry" of the present invention refers to the black goji berry of the plant genus Lycium in the Solanaceae family, also denoted as Lycium ruthenicum Murray. As the part to be used, there is of course no limitation, and the fruit (pulp, pericarp, etc.) is preferably used. The "black goji berry" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0055] The "quinoa" of the present invention refers to the quinoa of the plant genus Chenopodium in the Amaranthaceae family, including those also denoted as Chenopodium quinoa Willd. As the part to be used, there is of course no limitation, and the ear is preferably used. The "quinoa" of the present invention can be used as it is or those obtained through processing such as drying according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0056] The "radish" in the present invention refers to the radish of the plant species of the genus Raphanus in the Brassicaceae family, also denoted as Raphanus sativus L. As the part to be used, there is of course no limitation, and the seeds are preferably used. The "radish" in the present invention can be used as it is or after being processed such as by drying according to needs. When these are commercially available, commercially available products can also be used as long as commercially available products with the target effects of the present invention can be obtained.

[0057] The "Grifola frondosa" in the present invention refers to the Grifola frondosa, which is a mushroom of the genus Grifola in the family Polyporaceae, also denoted as Polyporus frondosus (Dicks.) Fr. [Boletus frondosus Dicks.]. As the part to be used, there is of course no limitation, and the fruiting body is preferably used. The "Grifola frondosa" in the present invention can be used as it is or after being processed such as by drying according to needs. When these are commercially available, commercially available products can also be used as long as commercially available products with the target effects of the present invention can be obtained.

[0058] The "Fagopyrum tataricum" in the present invention refers to the Fagopyrum tataricum, which is a plant species of the genus Fagopyrum in the Polygonaceae family, also denoted as Fagopyrum tataricum (L.) Gaertn. As the part to be used, there is of course no limitation, and the seeds are preferably used. The "Fagopyrum tataricum" in the present invention can be used as it is or after being processed such as by drying according to needs. When these are commercially available, commercially available products can also be used as long as commercially available products with the target effects of the present invention can be obtained.

[0059] The "Coprinus comatus" in the present invention refers to the Coprinus comatus, which is a mushroom of the genus Coprinus in the family Coprinaceae. As the part to be used, there is of course no limitation, and the fruiting body is preferably used. The "Coprinus comatus" in the present invention can be used as it is or after being processed such as by drying according to needs. When these are commercially available, commercially available products can also be used as long as commercially available products with the target effects of the present invention can be obtained.

[0060] The "blackberry" in the present invention refers to the blackberry (blackberry) of the plant species of the genus Rubus in the Rosaceae family, including those also denoted as Rubus fruticosus agg. As the part to be used, there is of course no limitation, and the leaves are preferably used. The "blackberry" in the present invention can be used as it is or after being processed such as by drying according to needs. When these are commercially available, commercially available products can also be used as long as commercially available products with the target effects of the present invention can be obtained.

[0061] The "nettle" of the present invention refers to the nettle of the plant genus Urtica in the family Urticaceae, also denoted as Urtica dioica L. As the part to be used, there is of course no limitation, and the leaves are preferred. The "nettle" of the present invention can be used as it is or after being processed such as dried according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0062] The "raspberry" of the present invention refers to the raspberry of the plant genus Rubus in the family Rosaceae, including those also denoted as Rubus idaeus L and Rubus strigosus. As the part to be used, there is of course no limitation, and the leaves are preferred. The "raspberry" of the present invention can be used as it is or after being processed such as dried according to needs. When these are commercially available, as long as commercially available products with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0063] According to one embodiment of the present invention, an extract is made using one or more selected from the group consisting of perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, ginseng, hibiscus sabdariffa, tea, chrysanthemum, dioscorea opposita, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, nettle and raspberry as a whole or a part thereof.

[0064] The method for manufacturing the above-mentioned extract is not particularly limited, and can be extracted according to the methods commonly used in this technical field. As the above-mentioned extraction method, there is of course no limitation, and examples thereof may include hot water extraction method, ultrasonic extraction method, filtration method, reflux extraction method, solvent (such as ethanol) extraction method, etc. These can be carried out alone or in combination of two or more methods. In addition, in order to obtain a high-purity extract, the extract can be further extracted one or more times each using the same method.

[0065] The type of extraction solvent used for manufacturing the above-mentioned extract is not particularly limited, and any solvent known in this technical field can be used as long as an extract with the target effects of the present invention can be obtained. Examples of such solvents, of course, are not limited, and may include, for example, water, alcohols with 1 to 4 carbon atoms, ethyl acetate, acetone, chloroform, etc., and these can be used in combination of two or more.

[0066] When the above-mentioned extract is commercially available, as long as an extract with the target effects of the present invention can be obtained, the commercially available products can also be used.

[0067] The blending amount of one or more extracts selected from the group consisting of extracts of Perilla frutescens, Taraxacum mongolicum, Camellia nitidissima, Codonopsis pilosula, Sophora japonica, Cistanche deserticola, Angelica dahurica, Pueraria lobata, Panax ginseng, Hibiscus sabdariffa, tea, Chrysanthemum morifolium, Dioscorea opposita, Hippohgae rhamnoides, Sambucus nigra, Olea europaea, Lycium ruthenicum, Chenopodium quinoa, Raphanus sativus, Grifola frondosa, Fagopyrum tataricum, Coprinus comatus, Rubus fruticosus, Urtica dioica, and Rubus idaeus contained in the composition of the present invention can be appropriately determined according to the use.

[0068] The "phenethyl isothiocyanate" of the present invention refers to a compound represented by the molecular formula C9H9NS (CAS registration number 2257-09-2). The "phenethyl isothiocyanate" of the present invention may be contained in cruciferous plants such as watercress, horseradish, and broccoli, but is not limited thereto.

[0069] The "thymoquinone" of the present invention refers to C 10 H 12 a compound represented by O2 (CAS registration number 490-91-5). The "thymoquinone" of the present invention may be contained in black cumin, etc., but is not limited thereto.

[0070] The blending amounts of phenethyl isothiocyanate and thymoquinone contained in the composition of the present invention are appropriately determined according to the use.

[0071] The composition of the present invention is of course not particularly limited and can be set as a food composition. When the composition for improving the intestinal barrier function or the composition for strengthening tight junctions of the present invention is set as a food composition, known ingredients (additives) that can be incorporated into food compositions can be further incorporated. Examples of such ingredients include sweeteners, high-intensity sweeteners (aspartame, sucralose, glycyrrhizin, saccharin, stevioside, (4-ethoxyphenyl)urea (Dulcin), sucralose, thaumatin, acesulfame potassium, etc.), flavors, colorants, acidulants, antioxidants, emulsifiers, preservatives, stabilizers, etc.

[0072] The food composition of the present invention can be a health functional food such as a nutritional functional food, a food for specified health use, a food with function claims, etc. In addition, it can be manufactured as a therapeutic food (i.e., a food that serves a therapeutic purpose or a food made by a dietitian, etc. based on a menu prepared according to a recipe made by a doctor), a diet therapy meal, a care meal, etc.

[0073] According to one embodiment of the present invention, there is provided one or more selected from the group consisting of perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, ginseng, hibiscus sabdariffa, tea, chrysanthemum, dioscorea opposita, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, urtica dioica, and raspberry, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol, preferably one or more selected from the group consisting of perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, tea, chrysanthemum, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, urtica dioica, and raspberry, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol, more preferably one or more selected from the group consisting of camellia nitidissima, cistanche deserticola, chrysanthemum, elderberry, olive, coprinus comatus, and urtica dioica, even more preferably one or more selected from the group consisting of camellia nitidissima, coprinus comatus, and urtica dioica for use in manufacturing a composition for improving the barrier function of the intestine. The above composition can be ingested by healthy individuals. In addition, the above composition can be made into a food composition, and the food composition can be a health care functional food such as a nutritional functional food, a specific health care food, or a functional labeled food. In addition, it can be made into a therapeutic food (i.e., a food that serves a therapeutic purpose, or a food prepared by a doctor's prescription and a dietitian according to the prescription and cooked based on the menu), a dietary therapy food, a nursing food, etc.

[0074] According to another embodiment of the present invention, there is provided a use of a composition in improving the barrier function of the intestine, the composition comprising one or more selected from the group consisting of perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, ginseng, hibiscus sabdariffa, tea, chrysanthemum, dioscorea opposita, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, urtica dioica, and raspberry, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol, preferably comprising one or more selected from the group consisting of perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, tea, chrysanthemum, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, urtica dioica, and raspberry, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymol, more preferably comprising one or more selected from the group consisting of camellia nitidissima, cistanche deserticola, chrysanthemum, elderberry, olive, coprinus comatus, and urtica dioica, and even more preferably comprising one or more selected from the group consisting of camellia nitidissima, coprinus comatus, and urtica dioica. The above composition can be ingested by healthy individuals. In addition, the above composition can be made into a food composition, and the food composition can be a health care functional food such as a nutritional functional food, a specific health care food, or a functional labeled food. In addition, it can be made into a therapeutic food (i.e., a food that serves a therapeutic purpose, or a food prepared by a dietitian according to a recipe prescribed by a doctor and based on that menu), a diet therapy food, a nursing food, etc.

[0075] Examples

[0076] The present invention will be specifically described based on the following examples, but the present invention is not limited by these examples. The content is expressed in mass% unless otherwise specified.

[0077] The following samples shown in Tables 1 and 2 were dissolved in DMSO (manufactured by Fujifilm Corporation) to prepare DMSO solutions of the samples at the concentrations shown in Tables 1 and 2 (concentrations at which no cytotoxicity was observed).

[0078] [Table 1]

[0079] Table 1: Names and concentrations of each sample

[0080]

[0081] [Table 2]

[0082] Table 2: Names and concentrations of each sample

[0083]

[0084] Cell culture

[0085] Caco-2 (HTB-37), a human intestinal epithelial cell line, was purchased from the American Type Culture Collection (Rockville, MD, USA) and cultured under the reported standard conditions (Non-Patent Documents 2 and 3). The cells were seeded at a density of 0.25×10 6 cells / cm 2 onto the permeable polyester membrane of a Transwell insert (12 mm in diameter, 0.4 μM pore size; Corning, Cambridge, MA, USA), and all experiments were performed on the 8th day after seeding. The culture medium was changed every 3 days. After 8 days of culture, the components were added as described below and the intestinal barrier function was measured.

[0086] Determination of intestinal barrier function

[0087] Based on the descriptions in Non-Patent Documents 8 and 9, the trans-epithelial electrical resistance (TER) of the Caco-2 monolayer through the Transwell insert was used to measure the TJ barrier function of the intestinal epithelium, and thus the intestinal barrier function was evaluated. The TER of the monolayer cells showed 1000 - 1300 Ω·cm 2 (data not shown). The DMSO solution of each prepared sample or the control (DMSO) was added to the apical side well, and the cells were incubated for 48 hours. This experiment was based on the following reports: 100 μM kaempferol, myricetin, and quercetin showed a protective effect on the TJ barrier function after 48 hours of addition (Non-Patent Documents 2 and 3). Before and 24 and 48 hours after the addition of the compound, the TER was measured using a Millicell-ERS system (Millipore, Bedford, MA, USA).

[0088] Statistical analysis

[0089] All values were expressed as mean ± SEM (n = 3 - 4). In addition, as the TER at each time point, the ratio relative to the initial value before addition was calculated, and the TER of each sample was shown in the form of a ratio relative to the control at each time point. For statistical analysis, a Student's t-test was performed. It was considered significant when P < 0.05 (vs control).

[0090] The results are shown in Table 3. In the case of Caco-2 cells supplemented with perilla, dandelion, camellia nitidissima, codonopsis pilosula, sophora japonica, cistanche deserticola, angelica dahurica, pueraria lobata, ginseng, hibiscus sabdariffa, tea, chrysanthemum, dioscorea opposita, seabuckthorn, elderberry, olive, lycium ruthenicum, quinoa, radish, grifola frondosa, tartary buckwheat, coprinus comatus, blackberry, urtica dioica, raspberry, phenethyl isothiocyanate or thymol, the TER was significantly higher than that of the control, indicating an improvement in intestinal barrier function.

[0091]

Table 3

[0092] Table 3: Evaluation results of each sample

[0093]

[0094] Determination of human intestinal barrier function

[0095] Evaluate the effect of urtica dioica on human intestinal barrier function. An open-label crossover comparative trial with placebo control was conducted on 11 healthy men aged 20 - 64 years. For the application of urtica dioica, it was carried out by ingesting the test food at a rate of 880 mg of urtica dioica leaves (equivalent to dry leaves) / day, and for the application of placebo, it was carried out by ingesting the control food at a rate of an equal amount of maltodextrin / day. The ingestion of the test food and the control food was carried out for 1 week each. Before and after the 1-week ingestion period of the test food or the control food, for each subject, urine was collected 6 hours after ingesting a mixture of 5 g of lactulose (L) and 1 g of mannitol (M). Using an LC / MS / MS device (API4000 Qtrap (SCIEX)), the lactulose / mannitol (L / M) ratio in urine was measured under the conditions shown in Table 4 below, and the mean ± standard error of the L / M ratio was calculated. A 1-week washout period was set between the application of placebo and the application of urtica dioica.

[0096]

Table 4

[0097] Table 4: LC / MS / MS measurement conditions

[0098]

[0099] The results are shown in Table 5 below.

[0100]

Table 5

[0101]

[0102] For the L / M ratio, statistical processing was performed by means of a corresponding Student's t-test. A p-value less than 0.05 was judged as a significant decrease in the L / M ratio, and a p-value of 0.05 or more and less than 0.1 was judged as a tendency towards a significant decrease in the L / M ratio. As a result, in Example 28 (Urtica dioica application group), the L / M ratio after application was significantly decreased compared with that before application (p-value = 0.046), while in Comparative Example 4 (placebo application group), the L / M ratio after application did not change compared with that before application. In addition, regarding the L / M ratio after application of Urtica dioica, statistical processing was performed by means of a corresponding Student's t-test, and as a result, there was a significant tendency for a decrease compared with the L / M ratio after application of the placebo (p-value = 0.058). The above results indicate that Urtica dioica improves the intestinal barrier function of humans.

Claims

1. A composition for improving intestinal barrier function, comprising one or more selected from the group consisting of Urtica dioica, Perilla frutescens, Taraxacum mongolicum, Camellia chrysantha, Codonopsis pilosula, Sophora japonica, Cistanche deserticola, Angelica dahurica, Pueraria lobata, Ginseng, Hibiscus sabdariffa, Tea, Chrysanthemum, Dioscorea zingiberensis, Seabuckthorn, Sambucus sambucus, Olive, Lycium ruthenicum, Quinoa, Radish, Grifola frondosa, Tartary buckwheat, Coprinus comatus, Blackberry and Raspberry and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymoquinone. 2 . The composition according to claim 1 , comprising one or more selected from the group consisting of Urtica dioica, Camellia chrysantha and Coprinus comatus.

3. The composition according to claim 1, which is used for strengthening tight junctions. The composition according to any one of claims 1 to 3, which is a food composition.

Images