Antiobesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strength enhancers, blood sugar level improvers, muscle strength enhancers, oral compositions, and cosmetic compositions

Abstract

Provided is an antiobesity agent, an anti-inflammatory agent, a brain function improver, a liver function improver, a bone strength enhancer, a blood sugar level improver, a muscle strength enhancer, and an oral composition and a cosmetic composition each containing at least any one of these, which contain, as an effective ingredient, a compound represented by the following general formula (1).[Chem. 1] (In general formula (1), R 1 represents H or a group represented by general formula (2). In general formula (2), * represents a bonding site.)

Description

Technical Field

[0001] This invention relates to anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar level improvers, muscle strengtheners, oral compositions, and cosmetic compositions. Background Technology

[0002] In recent years, due to lifestyle habits such as overeating and lack of exercise, body fat has increased, leading to obesity. This increase in obesity is not only occurring in humans but also in pets and livestock. Obesity can lead to adult diseases such as hyperlipidemia and arteriosclerosis, thus posing a significant health problem beyond just aesthetics.

[0003] Treatments for obesity, such as restricting dietary intake and burning fat through various aerobic exercises, are not only unlikely to be effective in the short term but also often involve physical and psychological discomfort, thus they cannot be considered effective methods. Therefore, methods using anti-obesity agents (e.g., pharmaceuticals, food and beverage products, animal feed, cosmetic compositions, etc.) are generally employed for the prevention and treatment of obesity.

[0004] As an effective ingredient in anti-obesity agents, substances that inhibit the activity of enzymes related to carbohydrate or fat metabolism, such as lipases and α-glucosidases, are used. Examples of substances with this inhibitory effect include, for example, catechins and plant extracts (see, for example, Patent Documents 1 and 2).

[0005] Inflammatory diseases such as contact dermatitis (macules), psoriasis, pemphigus vulgaris, atopic dermatitis, various other inflammatory skin diseases accompanied by rough skin, rheumatoid arthritis, osteoarthritis, asthma, etc., have diverse causes and pathogenesis. Known causes include the release of histamine and increased production of prostaglandin E2 (PGE2) (increased activity of cyclooxygenase-2 (COX-2)).

[0006] Histamine release is the phenomenon of histamine escaping from intracellular cells to extracellular space, triggering an inflammatory response. Therefore, researchers have attempted to prevent or treat allergic and inflammatory diseases by inhibiting or blocking substances that release histamine. However, directly evaluating histamine release is difficult; therefore, the release of aminohexosidase, which is known to release histamine simultaneously, can be used as an indicator. Thus, it can be argued that inhibiting the release of aminohexosidase can simultaneously inhibit histamine release, thereby potentially having an effect on the prevention, treatment, or improvement of inflammatory diseases.

[0007] Furthermore, histamine is known to mediate intercellular communication as a local messenger, increase gastric acid secretion in the digestive organs, and function as a neurotransmitter in the central nervous system, helping to maintain wakefulness. However, excessive free histamine can contribute to gastric ulcers due to excessive gastric acid in the digestive organs and to sleep disorders in the central nervous system. As mentioned above, by inhibiting the release of aminohexosidase, the release of histamine can also be inhibited, thus it is believed that it can prevent, treat, or improve gastric ulcers and sleep disorders caused by excessive gastric acid. Substances known to inhibit the release of aminohexosidase include, for example, extracts from vine tea (see, for example, Patent Document 3).

[0008] In recent years, an aging society has been emerging, leading to a growing desire for physical and mental well-being. As people age, their memory and learning abilities gradually decline. Furthermore, cognitive impairment due to neurodegeneration is a major problem in diseases such as Alzheimer's and Parkinson's. Simultaneously, the number of patients with cognitive problems, including depression and other mood disorders caused by various pressures from work, family, and interpersonal relationships, is increasing year by year.

[0009] Common methods for improving brain function include improving the nutrition and oxygen supply to brain nerve cells (such as increasing intracranial glucose and improving blood flow); improving neurotransmission in the synaptic cleft (supply of neurotransmitter precursors, increased release of neurotransmitters, activation of receptors, and inhibition of the conversion of released neurotransmitters).

[0010] In neurodegenerative diseases such as Alzheimer's and Parkinson's, protein wastes such as amyloid-β and α-synuclein accumulate without being removed from the brain, and this accumulation is considered a contributing factor to these neurodegenerative diseases. The lymphatic system helps remove protein waste from other parts of the body, but since it is not located in the brain, it was assumed that protein waste was broken down and removed there. However, recent studies have found that cerebrospinal fluid (CSF) flowing through the perivascular lumen and astrocytes in the brain helps remove protein waste, and waterchannel protein 4 (AQP4), highly expressed in astrocytes, significantly contributes to the flow of CSF (see Non-Patent Literature 1). Furthermore, reports indicate that CSF flow increases and the removal rate of amyloid-β is also enhanced during sleep and anesthesia (see Non-Patent Literature 2). This series of intracranial pathways has been termed the "lymphatic system" and has attracted considerable attention. Therefore, if the flow of this lymphatic system can be increased, protein waste such as amyloid β and α synuclein can be effectively removed from the brain, which is expected to promote the prevention, treatment or improvement of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Lewy body dementia, and multiple system atrophy.

[0011] Furthermore, it is becoming increasingly clear that the activation of astrocytes and microglia is associated with various impairments in brain function. For example, in the aging brain, microglia are in an activated state, leading to increased production of inflammatory cytokines (such as TNF-α, IL-6, IL-1β, etc.) and nitric oxide (NO), a neurodegenerative factor, thus contributing to neurodegenerative disorders (see, for example, Patent Document 4). It is known that the hyperactivity or chronicity of neurodegenerative disorders is associated not only with cognitive impairment and depression, but also with neurodegenerative diseases such as Alzheimer's and Parkinson's (see Non-Patent Document 3). Therefore, it is reasonable to assume that if neurodegenerative disorders can be inhibited, cognitive functions (memory or learning abilities, etc.) reduced due to aging and other neurodegenerative disorders can be improved. Furthermore, it is possible to prevent, treat, or improve cognitive impairment, mood disorders, and neurodegenerative diseases such as Alzheimer's and Parkinson's (see Non-Patent Document 4). On the other hand, interleukin-10 (IL-10) is known to function in the brain as a neuroprotective factor that inhibits neurological disorders (see Non-Patent Literature 5 and 6).

[0012] Besides metabolizing and storing various nutrients absorbed by the intestines, the liver also performs many functions essential for life, such as bile production, secretion, detoxification, and excretion, making it an extremely important organ for humans. However, due to various factors such as irregular lifestyle, stress, viruses, drugs, alcohol, malnutrition, and liver circulatory system disorders, the liver is prone to acute or chronic damage, sometimes leading to diseases such as acute hepatitis, chronic hepatitis, fatty liver, jaundice, and cirrhosis (liver dysfunction).

[0013] Glutathione is a tripeptide formed from three amino acids: glutamic acid, cysteine, and glycine. It is a compound in cells that mainly contains cysteine ​​residues. In the liver, glutathione not only protects hepatocytes from various oxidative stresses but also directly participates in liver function, such as drug metabolism, by forming complexes with harmful substances like drugs and reactive compounds, which are then excreted from the cells. However, it is known that the effects of glutathione are accompanied by its depletion. In fact, in rats, liver damage induced by galactosamine and other substances reduces the amount of glutathione in hepatocytes. Therefore, it is believed that promoting glutathione production in the liver could inhibit liver damage and thus improve liver function. Substances that promote glutathione production include hot water extracts of amber (e.g., see Patent Document 5).

[0014] Furthermore, replenishing cells with the energy required for cell division is crucial for promoting cell proliferation. ATP is an example of an organism's energy source, and it is believed that increasing ATP production promotes intracellular energy metabolism, leading to cell proliferation. However, reports indicate that cells with declining function and aging cells contain less ATP than normal cells (see, for example, Patent Document 6). Therefore, it is argued that promoting ATP production within cells could activate them, promote cell division, and restore their proliferative capacity.

[0015] Bone is a tissue primarily composed of hydroxyapatite (a form of calcium phosphate) and type I collagen. It not only supports our bodies but also plays a vital role in maintaining blood calcium levels and facilitating blood production. Bone is formed by osteoblasts differentiated from mesenchymal stem cells through the calcification of bone matrix proteins and matrix vesicles, and is subsequently absorbed (destroyed) by osteoclasts. This constant cycle of formation and resorption (destruction) (bone remodeling) within bone, through balanced bone metabolism, maintains normal bone density (see Non-Patent Literature 7).

[0016] The report notes that due to the aging population and changes in diet and lifestyle in recent years, the balance of bone remodeling has been disrupted, leading to an increase in patients with bone diseases. Osteoporosis is a representative example of bone-related diseases, primarily caused by excessive bone resorption leading to decreased bone density. Besides osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontal disease are also bone-related diseases closely related to abnormal bone remodeling.

[0017] Therefore, it is believed that by promoting bone formation and correcting abnormalities in bone remodeling, it is possible to prevent, treat, and improve bone-related diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontitis. Known components that promote bone formation include royal jelly, glucosamine, and chondroitin sulfate (see Patent Document 7).

[0018] Dipeptidyl peptidase IV (hereinafter sometimes referred to as "DPPIV") is a serine protease that recognizes the second proline or alanine residue from its N-terminus and has enzymatic activity that cleaves its C-terminal side. DPPIV is expressed on the cell surface of epithelial and endothelial cells in tissues such as the kidney, liver, intestine, and placenta, as well as T cells, and is believed to be related to various physiological phenomena through its enzymatic activity.

[0019] As a matrix for DPPIV, hormones known as incretins can be cited. Incretins are a collective term for hormones secreted by the intestines in a glucose-dependent manner by nutrient stimulation, promoting insulin secretion from pancreatic β-cells. Known examples include GLP-1 and GIP. These incretins not only promote glucose-dependent insulin secretion but also inhibit glucagon secretion from pancreatic α-cells, lower blood pressure, inhibit gastric emptying, and subsequently act on the hypothalamus to suppress appetite (see Non-Patent Literature 8). However, since incretins are broken down by DPPIV, for example, GLP-1 has a known half-life of approximately 1.5 minutes in vivo. Therefore, if the enzymatic activity of DPPIV can be inhibited, the half-life of incretins in vivo can be prolonged. Thus, through the aforementioned effects of incretins, they hold promise for the treatment of type 2 diabetes, obesity, hypertension, and insulin resistance.

[0020] Furthermore, DPPIV is known to be identical to CD26, a marker of T-cell activation, and its activity is controlled by a matrix of various immunomodulatory peptides. Therefore, it can be considered that controlling DPPIV activity can control immune responses such as autoimmune diseases like rheumatoid arthritis and transplant rejection. Moreover, DPPIV is known to be associated with the metabolism of several neuropeptides and growth hormone; invasion, metastasis, and angiogenesis in cancer; and HIV infection of lymphocytes. Therefore, inhibiting DPPIV activity could treat neurological disorders such as pain, neurodegenerative diseases, and neuropsychiatric disorders (e.g., sciatica, Alzheimer's disease, depression); growth hormone deficiency and diseases treated with growth hormone; cancers such as T-cell lymphoma, acute lymphoblastic leukemia, thyroid cancer, basal cell carcinoma, breast cancer; and HIV infection (AIDS).

[0021] When exercising, muscles are responsible for movement, and to improve athletic performance, it's necessary to strengthen muscle function. This isn't limited to athletes; for ordinary people, muscles are crucial for a healthy daily life, such as engaging in light exercise and maintaining posture. Furthermore, muscles not only move the body but also perform various other functions, such as controlling blood sugar levels through glucose utilization, regulating body temperature through thermodynamics, and regulating fat mass through lipid utilization. Therefore, they are considered essential for maintaining health.

[0022] In muscle, mononuclear myoblasts fuse to form elongated, multinucleated myotube cells. These myotube cells then aggregate and arrange themselves to form muscle fibers, generating the powerful force of muscle. As described above, muscle formation is a complex process involving the proliferation and differentiation of myoblasts, the recognition and adhesion between muscle cells, and fusion. Medium-chain fatty acids such as decenoic acid, decanoic acid, decenoic acid, and sebacic acid are known to promote myoblast proliferation (see, for example, Patent Document 8).

[0023] Existing technical documents Patent documents Patent Document 1: Japanese Patent Application Publication No. 2016-027812 Patent Document 2: Japanese Patent Application Publication No. 2012-051916 Patent Document 3: Japanese Patent Application Publication No. 2003-012532 Patent Document 4: Japanese Patent Application Publication No. 2022-183626 Patent Document 5: Japanese Patent Application Publication No. 2010-235551 Patent Document 6: Japanese Patent Application Publication No. 2003-321373 Patent Document 7: Japanese Patent Application Publication No. 2019-062931 Patent Document 8: Japanese Patent Application Publication No. 2020-089278 Non-patent literature Non-patent literature 1: Jeffrey J Iliff et al., Sci Transl Med., 2012, Vol.4, issue 147, pp.147ra111 Non-patent literature 2: Lulu Xie et al., Science, 2013, Vol. 342, issue 6156, pp. 373-377 Non-patent literature 3: Akio Tsukimura, Clinical Neurology, 2014, Vol. 54, No. 12, pp. 1119-1121 Non-patent literature 4: Akira Motoshi, Journal of Psychoneurology, 2012, Vol. 114, No. 2, pp. 124-133 Non-patent literature 5: Diana M. Norden et al., Glia, 2014, Vol. 62, issue 6, pp. 881-895 Non-patent literature 6: Anton Reiner et al., Int. J. Mol. Sci., 2015, Vol. 16, issue 1, pp. 758-787 Non-patent literature 7: Takeda Hide, Journal of the Japanese Medical Association, 2014, Vol. 56, No. 8, pp. 1188-1195. Non-patent literature 8: Nobuyuki Yasuda et al., Japanese Journal of Pharmacology, 2005, Vol. 125, No. 6, pp. 379-384 Summary of the Invention

[0024] The problem that the invention aims to solve The purpose of this invention is to provide an anti-obesity agent with excellent anti-obesity effects and high safety, an anti-inflammatory agent with excellent anti-inflammatory effects and high safety, a brain function improver with excellent brain function enhancement effects and high safety, a liver function improver with excellent liver function enhancement effects and high safety, a bone strengthening agent with excellent bone strengthening effects and high safety, a blood glucose level improver with excellent blood glucose level improvement effects and high safety, a muscle strengthening agent with excellent muscle strengthening effects and high safety, as well as oral and cosmetic compositions containing these.

[0025] Methods for solving problems The method for solving the above-mentioned problem is as follows. That is, <1> An anti-obesity agent, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0026] [Chemistry 1] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0027] [Chemistry 2] In the above general formula (2), * represents a bonding bond.

[0028] <2> An anti-inflammatory agent, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0029] [Chemistry 3] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0030] [Chemistry 4] In the above general formula (2), * represents a bonding bond.

[0031] <3> A brain function improver, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0032] [Chemistry 5] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0033] [Chemistry 6] In the above general formula (2), * represents a bonding bond.

[0034] <4> A liver function improver, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0035] [Chemistry 7] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0036] [Chemistry 8] In the above general formula (2), * represents a bonding bond.

[0037] <5> A bone strengthening agent, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0038] [Chemistry 9] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0039] [Chemistry 10] In the above general formula (2), * represents a bonding bond.

[0040] <6> A blood glucose level improver, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0041] [Chemistry 11] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0042] [Chemistry 12] In the above general formula (2), * represents a bonding bond.

[0043] <7> A muscle enhancer, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0044] [Chemistry 13] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0045] [Chemistry 14] In the above general formula (2), * represents a bonding bond.

[0046] <8> An oral composition, characterized in that it contains at least one selected from the group consisting of the anti-obesity agent described in <1>, the anti-inflammatory agent described in <2>, the brain function improver described in <3>, the liver function improver described in <4>, the bone enhancer described in <5>, the blood glucose improver described in <6>, and the muscle enhancer described in <7>.

[0047] <9> A cosmetic composition, characterized in that it contains at least one selected from the group consisting of the anti-obesity agent described in <1>, the anti-inflammatory agent described in <2>, the brain function improver described in <3>, the liver function improver described in <4>, the bone strengthener described in <5>, the blood glucose improver described in <6>, and the muscle strengthener described in <7>.

[0048] The effects of the invention According to the present invention, it is possible to provide an anti-obesity agent with excellent anti-obesity effect and high safety, an anti-inflammatory agent with excellent anti-inflammatory effect and high safety, a brain function improving agent with excellent brain function improving effect and high safety, a liver function improving agent with excellent liver function improving effect and high safety, a bone strengthening agent with excellent bone strengthening effect and high safety, a blood glucose level improving agent with excellent blood glucose level improving effect and high safety, a muscle strengthening agent with excellent muscle strengthening effect and high safety, as well as oral compositions and cosmetic compositions containing the thereof. Detailed Implementation

[0049] (Anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar level improvers, and muscle strengtheners) The anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone enhancer, the blood glucose improver, and the muscle enhancer of the present invention each contain a compound represented by the following general formula (1) as an active ingredient, and further contain other ingredients as needed.

[0050] [Chemistry 15] In the above general formula (1), R 1It represents H or the group represented by the following general formula (2).

[0051] [Chemistry 16] In the above general formula (2), * represents a bonding bond.

[0052] <<Compounds represented by general formula (1)>> Examples of compounds represented by the general formula (1) above include, for example, the aforementioned R. 1 Mangiferin, which is the group represented by the above general formula (2) and the following structural formula (1), wherein the above R 1 The following structural formula (2) shows mangiferin (Norathyriol), etc., which are H. They can be used alone or in combination with more than two.

[0053] [Chemistry 17] [Chemistry 18] -mangiferin- The mangiferin shown in the above structural formula (1) is a C-glycoside abundant in plants such as mango, sedge, and tangerine. C-glycosides are extremely stable because the carbon of the sugar is bonded to the carbon of the compound through a carbon-carbon bond.

[0054] The aforementioned mangiferin can be commercially available, mangiferin prepared from plants using known methods, or mangiferin prepared through organic synthesis using known methods. Furthermore, the aforementioned mangiferin can be a refined product or an unrefined or crudely refined product prepared from plants containing components other than mangiferin.

[0055] Commercially available products containing the aforementioned mangiferin include, for example, M3547 (batch number: SLBQ6689V, manufactured by SIGMA).

[0056] -mangiferin- The mangiferin shown in the above structural formula (2) is the ligand of mangiferin.

[0057] The aforementioned mangiferin can be a commercially available product or mangiferin manufactured according to known methods. Furthermore, the aforementioned mangiferin can be a refined product or an unrefined or crudely refined product containing components other than mangiferin.

[0058] Commercially available products containing the aforementioned mangiferin include, for example, ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA).

[0059] There are no particular limitations on the method for producing the aforementioned mangiferin, and a suitable method can be selected from known methods, such as chemical methods or microbial conversion methods using microorganisms. From an environmental point of view, the microbial conversion method is preferred for producing the aforementioned mangiferin.

[0060] Examples of chemical methods mentioned above include organic synthesis and decomposition of acid catalysts.

[0061] Examples of microbial conversion methods include those using Bacteroides sp. MANG strain (see Sanugul K et al., Biol. Pharm. Bull., 2005, Vol. 28, issue 9, pp. 1672-1678), Lachnospiraceae CG19-1 strain (see Braune A et al., Environmental Microbiology, 2011, Vol. 13, issue 2, pp. 482-494), and Bacillus sp. KM7-1 strain (see Japanese Patent Application Laid-Open No. 2022-001026) to convert mangiferin to mangiferin. Among these, the method using Bacillus sp. KM7-1 strain is preferred because it allows for the simple, efficient, safe, and environmentally friendly production of mangiferin.

[0062] <<Other Ingredients>> Other components in the aforementioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar improvers, and muscle strengtheners can be appropriately selected according to the purpose, provided they do not impair the effects of the present invention. Examples include excipients, moisture-proofing agents, preservatives, strengthening agents, thickeners, emulsifiers, antioxidants, sweeteners, acidulants, seasonings, colorants, fragrances, whitening agents, moisturizers, oily components, ultraviolet absorbers, surfactants, thickeners, alcohols, powder components, colorants, aqueous components, water, and skin nutrients. One of these components can be used alone, or two or more can be used in combination.

[0063] The content of the other components in the above-mentioned anti-obesity agent, anti-inflammatory agent, brain function improver, liver function improver, bone enhancer, blood sugar level improver, and muscle enhancer is not particularly limited and can be appropriately selected according to the purpose, as long as it does not impair the effect of the present invention.

[0064] The following describes one embodiment of the effects of the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthening agent, the blood glucose level improver, and the muscle strengthening agent of the present invention. Furthermore, the present invention is not limited to the following embodiment; modifications, additions, or deletions can be made in other embodiments within the scope conceived by those skilled in the art. Any embodiment that achieves the effects of the present invention is included within the scope of the present invention.

[0065] <Anti-obesity agents> The compound represented by the above general formula (1), which is the effective component of the anti-obesity agent of the present invention, has at least one function selected from the group consisting of α-glucosidase activity inhibition and lipase activity inhibition, and can be used as the effective component of the above-mentioned anti-obesity agent by utilizing their functions.

[0066] Therefore, the above-mentioned anti-obesity agents have at least one effect selected from the group consisting of α-glucosidase activity inhibition and lipase activity inhibition.

[0067] Alpha-glucosidase is an enzyme that catalyzes the hydrolysis of sugars by the α-1,4-glucosidase combination. It is a digestive enzyme expressed as a membrane enzyme in the epithelial cells of the small intestine of mammals. Among α-glucosidases, those that break down maltose into glucose are called maltase, and those that break down sucrose into glucose are called sucrase. Thus, α-glucosidase participates in the metabolism of carbohydrates and fats in the body; therefore, inhibiting its activity can exert an anti-obesity effect.

[0068] Lipases are enzymes that hydrolyze the ester bonds that make up lipids. In mammals, they are synthesized by the pancreas and secreted into pancreatic juice. They are digestive enzymes that hydrolyze triglycerides (neutral fats). Thus, lipases participate in the metabolism of fat in the body, and therefore, inhibiting their activity can exert an anti-obesity effect.

[0069] The compound represented by the above general formula (1) has at least one of excellent α-glucosidase activity inhibition and excellent lipase activity inhibition, and its usefulness as an anti-obesity agent was previously completely unknown, which is a new understanding of the inventors.

[0070] The above-mentioned anti-obesity agents inhibit α-glucosidase activity. In the presence of α-glucosidase and its matrix (e.g., maltose, sucrose, etc.), the amount of glucose is reduced when the above-mentioned anti-obesity agents are added compared to the amount of glucose without the addition of the above-mentioned anti-obesity agents. Therefore, the above-mentioned anti-obesity agents have an inhibitory effect on α-glucosidase activity, which confirms that they are useful as anti-obesity agents.

[0071] The above-mentioned glucose levels can be determined using commercially available kits for the determination of α-glucosidase activity inhibition (e.g., glucose CII-TestWako, manufactured by Fujifilm and Kojun Pharmaceutical Co., Ltd.).

[0072] The aforementioned anti-obesity agent inhibits the α-glucosidase activity of the subject, which can be confirmed, for example, by comparing serum glucose concentrations before and after administration of the anti-obesity agent to the subject. Specifically, if the serum glucose concentration after administration of the anti-obesity agent is lower than the serum glucose concentration before administration, it can be determined that the anti-obesity agent inhibits α-glucosidase activity.

[0073] The lipase activity inhibition effect of the above-mentioned anti-obesity agent is demonstrated when the amount of BAL in the presence of lipase and its matrix (e.g., BALB, etc.) is reduced compared to the amount of BALB hydrolysate in the absence of the above-mentioned anti-obesity agent, thus confirming the usefulness of the anti-obesity agent.

[0074] The above-mentioned BAL amount can be measured using commercially available reagents for lipase activity assay (e.g., lipase kit S, manufactured by Sumitomo Phenolic Resin Co., Ltd.).

[0075] The content of the compound represented by the above general formula (1) in the aforementioned anti-obesity agent is not particularly limited as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose. The content of mangiferin in the aforementioned anti-obesity agent relative to the total amount of the aforementioned anti-obesity agent is preferably 100 μmol / L or more, more preferably 200 μmol / L or more. Furthermore, the content of mangiferin in the aforementioned anti-obesity agent relative to the total amount of the aforementioned anti-obesity agent is preferably 100 μmol / L or more, more preferably 200 μmol / L or more.

[0076] The aforementioned anti-obesity agent can be the compound represented by the general formula (1) above. Furthermore, there is no particular limitation on the ratio of mangiferin to mangiferin in the aforementioned anti-obesity agent; either one may be present, or a ratio of two may be appropriately selected. Additionally, the content of the compound represented by the general formula (1) in the aforementioned anti-obesity agent is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0077] In addition, the present invention also includes α-glucosidase activity inhibitors containing compounds of the above general formula (1) as active ingredients and lipase activity inhibitors containing compounds of the above general formula (1) as active ingredients.

[0078] <Anti-inflammatory agents> The compound represented by the above general formula (1), which is the effective component of the anti-inflammatory agent of the present invention, has at least one function selected from the group consisting of inhibition of free aminohexosidase and inhibition of prostaglandin E2 (PGE2) production, and can be used as the effective component of the above-mentioned anti-inflammatory agent by utilizing their functions.

[0079] Therefore, the above-mentioned anti-inflammatory agents have at least one effect selected from the group consisting of free inhibition of aminohexosidase and inhibition of PGE2 production.

[0080] Aminohexosidase is an enzyme that hydrolyzes N-acetyl-D-hexosamine residues from N-acetyl-D-hexosamine and is locally present in lysosomes in mammals. It is known that aminohexosidase is released simultaneously with histamine; inhibiting the release of aminohexosidase also inhibits the release of histamine. Therefore, inhibiting the release of aminohexosidase exerts an anti-inflammatory effect.

[0081] PGE2 is a physiologically active substance biosynthesized from arachidonic acid, one of the unsaturated fatty acids. Known physiological functions of PGE2 include fever, pain, vasodilation, and labor. Therefore, inhibiting PGE2 production can exert an anti-inflammatory effect.

[0082] The compound represented by the above general formula (1) has at least one of excellent inhibition of aminohexosidase free activity and excellent inhibition of PGE2 production, and its usefulness as an anti-inflammatory agent was previously completely unknown, which is a new understanding of the inventors.

[0083] The inhibitory effect of the aforementioned anti-inflammatory agent on aminohexosidase can be measured in the presence of aminohexosidase by the absorbance at a wavelength of 415 nm between p-nitrophenyl N-acetylβ-D-glucosamine (p-NAG), which serves as the substrate for aminohexosidase, and p-nitrophenol (PNP), which is released during the reaction. That is, the lower the absorbance, the more the release of aminohexosidase is inhibited. Specifically, when cells, preferably basophilic leukemia cells, are cultured in both the culture supernatant obtained in the presence of the aforementioned anti-inflammatory agent and the culture supernatant obtained in the absence of the aforementioned anti-inflammatory agent, and then reacted with p-NAG, if the absorbance of PNP in the culture supernatant obtained in the presence of the aforementioned anti-inflammatory agent is lower than that in the culture supernatant obtained in the absence of the aforementioned anti-inflammatory agent, it can be confirmed that the aforementioned anti-inflammatory agent has an inhibitory effect on aminohexosidase and is useful as an anti-inflammatory agent.

[0084] The aforementioned anti-inflammatory agents have an inhibitory effect on the free aminohexosidase of the subject, which can be confirmed, for example, by comparing the serum aminohexosidase activity before and after administration of the aforementioned anti-inflammatory agent to the subject. Specifically, if the serum aminohexosidase activity after administration of the aforementioned anti-inflammatory agent is lower than the serum aminohexosidase activity before administration, it can be confirmed that the aforementioned anti-inflammatory agent has an inhibitory effect on the free aminohexosidase, and is useful as an anti-inflammatory agent.

[0085] Serum aminohexosidase activity can be measured, for example, using commercially available aminohexosidase activity assay kits (e.g., Beta Hexosaminidase Activity Assay Kit, manufactured by Cosmo Bio Co., Ltd.).

[0086] The PGE2 production inhibition effect of the above-mentioned anti-inflammatory agent is confirmed to be that the PGE2 production level is reduced when the above-mentioned anti-inflammatory agent is added, compared to the PGE2 level without the addition of the above-mentioned anti-inflammatory agent. Therefore, the above-mentioned anti-inflammatory agent is useful as an anti-inflammatory agent.

[0087] The above-mentioned PGE2 levels can be measured using commercially available PGE2 assay kits (e.g., PGE2 EIA Kit, manufactured by Cayman Chemical).

[0088] The aforementioned anti-inflammatory agent has an inhibitory effect on PGE2 production in the subject, which can be confirmed, for example, by comparing the PGE2 production levels before and after administration of the anti-inflammatory agent to the subject. Specifically, the PGE2 production levels in samples such as serum, saliva, urine, or blood are measured before and after administration of the anti-inflammatory agent. If the PGE2 production level in the sample after administration of the anti-inflammatory agent is reduced compared to the PGE2 production level in the sample before administration, it can be determined that the anti-inflammatory agent has an inhibitory effect on PGE2 production.

[0089] The content of the compound represented by the above general formula (1) in the above-mentioned anti-inflammatory agent is not particularly limited as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0090] In particular, considering the inhibitory effect of the aforementioned anti-inflammatory agent on the free release of aminohexosidase, the content of mangiferin in the aforementioned anti-inflammatory agent relative to the total amount of the aforementioned anti-inflammatory agent is preferably 6 μmol / L or more, more preferably 25 μmol / L or more, and even more preferably 100 μmol / L or more. Furthermore, considering the inhibitory effect on the free release of aminohexosidase, the content of mangiferin in the aforementioned anti-inflammatory agent is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0091] Furthermore, considering the inhibitory effect on PGE2 production, the content of mangiferin in the aforementioned anti-inflammatory agent relative to the total amount of the aforementioned anti-inflammatory agent is preferably 10 μmol / L or more and 20 μmol / L or less, more preferably 12 μmol / L or more and 15 μmol / L or less. Furthermore, considering the inhibitory effect on PGE2 production, the content of mangiferin in the aforementioned anti-inflammatory agent relative to the total amount of the aforementioned anti-inflammatory agent is preferably 3 μmol / L or more, more preferably 6 μmol / L or more, even more preferably 12 μmol / L or more, even more preferably 25 μmol / L or more, and particularly preferably 50 μmol / L or more. Additionally, the content of mangiferin in the aforementioned anti-inflammatory agent is preferably high from the perspective of inhibiting PGE2 production; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0092] Furthermore, the aforementioned anti-inflammatory agent can be the compound represented by the general formula (1) itself. Moreover, there is no particular limitation on the ratio of mangiferin to mangiferin in the aforementioned anti-inflammatory agent; either one may be present, or both may be present in an appropriately selected ratio. From the perspective of inhibiting the free release of aminohexosidase by the aforementioned anti-inflammatory agent, the presence of mangiferin is preferred. Furthermore, from the perspective of inhibiting PGE2 production by the aforementioned anti-inflammatory agent, the presence of both mangiferin and mangiferin is preferred, and the presence of mangiferin is more preferred.

[0093] In addition, the present invention also includes an aminohexosidase free inhibitor containing the compound shown in the above general formula (1) as an active ingredient, and a PGE2 production inhibitor containing the compound shown in the above general formula (1) as an active ingredient.

[0094] Brain function improver The compound represented by the above general formula (1), which is an effective component of the brain function improver of the present invention, has at least one of the following effects: promoting cell proliferation of astrocytes, promoting the mRNA expression of aquaporin 4 (AQP4) in astrocytes, inhibiting the production of tumor necrosis factor (TNF-α) in microglia, inhibiting the expression of inflammatory inducing factor-related genes in microglia, and increasing the expression of inflammatory suppressor factor-related genes in microglia. It can be used as an effective component of the above-mentioned brain function improver by utilizing these effects.

[0095] Therefore, the aforementioned brain function improvers have at least one of the following effects: promoting cell proliferation of astrocytes, promoting the mRNA expression of aquaporin 4 (AQP4) in astrocytes, inhibiting the production of TNF-α in microglia, inhibiting the expression of inflammatory inducing factor-related genes in microglia, and increasing the expression of inflammatory suppressor-related genes in microglia.

[0096] As mentioned above, it is known that cerebrospinal fluid and perivascular cavities flowing through astrocytes, a type of glial cell, facilitate the removal of protein waste. High expression of AQP4, which is present in the aquatic channels of astrocytes, significantly increases the flow of cerebrospinal fluid. Therefore, promoting astrocyte proliferation and / or AQP4 mRNA expression can enhance brain function.

[0097] Furthermore, as mentioned above, when microglia, a type of glial cell, become activated, the production of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, etc.) is enhanced, contributing to neurological disorders. Therefore, by inhibiting the production of these inflammatory cytokines in microglia and / or suppressing the expression of inflammation-related genes, it is possible to improve brain function.

[0098] Here, in this invention, the inhibitory effect of the above-mentioned brain function improver on the expression of inflammation-inducing factor-related genes in microglia refers to the inhibition of the expression of at least one inflammation-inducing factor-related gene selected from the group consisting of TNF-α, iNOS, IL-6, IL-1β, IL-12, and CXCL2 in microglia, preferably the inhibition of mRNA expression.

[0099] Furthermore, in this invention, the increased expression of inflammation-suppressing factor-related genes in microglia using the aforementioned brain function improver refers to the increased expression of at least one inflammation-suppressing factor-related gene selected from the group consisting of IL-10 and IL-18 in microglia, preferably mRNA.

[0100] In addition, "the increased expression of inflammation-suppressing factor-related genes in microglia" refers to the increased expression of at least one inflammation-suppressing factor-related gene selected from the group consisting of IL-10 and IL-18 in activated microglia when the aforementioned brain function modifiers are effective, compared to the expression of at least one inflammation-suppressing factor-related gene selected from the group consisting of IL-10 and IL-18 in activated microglia when the aforementioned brain function modifiers are effective.

[0101] The compound represented by the above general formula (1) has at least one of the following effects: excellent cell proliferation promotion of astrocytes, excellent astrocyte AQP4 mRNA expression promotion, excellent microglial TNF-α production inhibition, excellent microglial inflammatory factor-related gene expression inhibition, and excellent microglial inflammatory factor-related gene expression enhancement. It is useful as a brain function improver and was previously completely unknown. This is a new understanding of the inventors.

[0102] When the number of astrocytes increased after the addition of the aforementioned brain function improver compared to the number of astrocytes before the addition of the brain function improver, it can be confirmed that the aforementioned brain function improver has a cell proliferation promoting effect on astrocytes and is useful as a brain function improver.

[0103] The number of astrocytes mentioned above can be determined using the MTT assay.

[0104] The above-mentioned brain function improver showed a promoting effect on AQP4 mRNA expression in astrocytes. Compared with the expression level of AQP4 mRNA in astrocytes before the addition of the above-mentioned brain function improver, the expression level of AQP4 mRNA in astrocytes increased after the addition of the above-mentioned brain function improver. Therefore, it can be confirmed that the above-mentioned brain function improver has a promoting effect on AQP4 mRNA expression in astrocytes and is useful as a brain function improver.

[0105] The expression level of AQP4 mRNA in the aforementioned astrocytes could be determined using a two-step RT-PCR method.

[0106] When the inhibitory effect of the above-mentioned brain function improver on the production of TNF-α in microglia is reduced compared to the amount of TNF-α produced in microglia before the addition of the above-mentioned brain function improver, it can be confirmed that the above-mentioned brain function improver has an inhibitory effect on the production of TNF-α in microglia and is useful as a brain function improver.

[0107] The amount of TNF-α produced by the aforementioned microglia can be measured using a sandwich ELISA method.

[0108] The inhibitory effect of the above-mentioned brain function improver on the expression of inflammation-inducing factor-related genes in microglia, compared with the expression level of inflammation-inducing factor-related genes in microglia before the addition of the above-mentioned brain function improver, shows that the expression level of inflammation-inducing factor-related genes in microglia is reduced after the addition of the above-mentioned brain function improver. Therefore, it can be confirmed that the above-mentioned brain function improver has an inhibitory effect on the expression of inflammation-inducing factor-related genes in microglia and is useful as a brain function improver.

[0109] The expression levels of the aforementioned inflammatory inducing factor-related genes in microglia can be determined using a two-step RT-PCR method.

[0110] The above-mentioned brain function improver has the effect of increasing the expression of inflammation-inhibiting factor-related genes in microglia. Compared with the expression level of inflammation-inhibiting factor-related genes in activated microglia when the above-mentioned brain function improver is ineffective, the expression level of inflammation-inhibiting factor-related genes in activated microglia when the above-mentioned brain function improver is increased. Therefore, it can be confirmed that the above-mentioned brain function improver has the effect of increasing the expression of inflammation-inhibiting factor-related genes in microglia, and is useful as a brain function improver.

[0111] The expression levels of the aforementioned genes related to inflammatory suppressor factors in microglia can be determined using a two-step RT-PCR method.

[0112] The content of the compound represented by the above general formula (1) in the above-mentioned brain function improver is not particularly limited as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0113] In particular, considering the astrocyte proliferation-promoting effect of the aforementioned brain function improver, the content of mangiferin in the aforementioned brain function improver relative to the total amount of the aforementioned brain function improver is preferably 25 μmol / L or more, more preferably 100 μmol / L or more. Furthermore, considering the astrocyte proliferation-promoting effect of the aforementioned brain function improver, the content of mangiferin in the aforementioned brain function improver relative to the total amount of the aforementioned brain function improver is more preferably 100 μmol / L or more. Additionally, considering the astrocyte proliferation-promoting effect, the content of the compound represented by the aforementioned general formula (1) in the aforementioned brain function improver is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0114] Furthermore, considering the promoting effect of the aforementioned brain function improver on AQP4 mRNA expression in astrocytes, the content of the compound represented by the aforementioned general formula (1) in the aforementioned brain function improver, relative to the total amount of the aforementioned brain function improver, is preferably 6 μmol / L or more, more preferably 25 μmol / L or more, and particularly preferably 100 μmol / L or more. Additionally, considering the promoting effect of the aforementioned brain function improver on AQP4 mRNA expression in astrocytes, the content of mangiferin in the aforementioned brain function improver is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0115] Furthermore, considering the inhibitory effect of the aforementioned brain function improver on TNF-α production, the content of mangiferin in the aforementioned brain function improver relative to the total amount of the aforementioned brain function improver is preferably 25 μmol / L or more, more preferably 100 μmol / L or more. Additionally, considering the inhibitory effect on TNF-α production, the content of mangiferin in the aforementioned brain function improver is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0116] Furthermore, considering the inhibitory effect of the brain function improver on the expression of inflammatory inducing factor-related genes and the upregulation effect of the brain function improver on the expression of inflammatory suppressor-related genes in microglia, the content of the compound represented by the above general formula (1) in the brain function improver relative to the total amount of the brain function improver is preferably 6 μmol / L or more, more preferably 25 μmol / L or more, and even more preferably 100 μmol / L or more. In addition, considering the inhibitory effect of the brain function improver on the expression of inflammatory inducing factor-related genes and the upregulation effect of the brain function improver on the expression of inflammatory suppressor-related genes in microglia, the content of the compound represented by the above general formula (1) in the brain function improver is preferably high, but there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0117] Furthermore, the aforementioned brain function improver can be the compound represented by the general formula (1) above. Moreover, the ratio of mangiferin to mangiferin in the aforementioned brain function improver is not particularly limited; either one may be present, or both may be present in an appropriately selected ratio, with mangiferin being preferred.

[0118] In addition, the present invention also includes a cell proliferation promoter of astrocytes containing the compound shown in the above general formula (1) as an active ingredient, an mRNA expression promoter of aquaporin 4 (AQP4) of astrocytes containing the compound shown in the above general formula (1) as an active ingredient, an inhibitor of TNF-α production of microglia containing the compound shown in the above general formula (1) as an active ingredient, and an expression enhancer of inflammation-inhibiting factor-related genes of microglia containing the compound shown in the above general formula (1) as an active ingredient.

[0119] <Liver Function Improvers> The compound represented by the following general formula (1), which is the effective component of the liver function improver of the present invention, has at least one effect selected from the group consisting of glutathione production promotion, ATP (adenosine triphosphate) production promotion, and hepatocyte proliferation promotion, and can be used as the effective component of the above-mentioned liver function improver by utilizing these effects.

[0120] Therefore, the above-mentioned liver function improvers have at least one effect selected from the group consisting of glutathione production promotion, ATP production promotion, and hepatocyte proliferation promotion.

[0121] As mentioned above, glutathione in the liver, besides protecting hepatocytes from various oxidative stresses, also contributes to liver function by forming harmful substances and compounds such as drugs and reactive compounds, and facilitating their excretion from cells. Therefore, promoting glutathione production in the liver can enhance liver function.

[0122] As described above, ATP provides cells with the energy needed for cell division, promoting cell proliferation. Therefore, by promoting ATP production in the liver, hepatocyte proliferation is promoted, thereby enhancing liver function.

[0123] The compound represented by the above general formula (1) has at least one of excellent glutathione production promotion, excellent ATP production promotion, and excellent hepatocyte proliferation promotion, and is useful as a liver function improver. This was previously completely unknown and is a new understanding of the inventors.

[0124] The above-mentioned liver function improver has a glutathione-promoting effect. Compared with the total glutathione level without the addition of the above-mentioned liver function improver, the total glutathione level increased when the above-mentioned liver function improver was added. Therefore, it can be confirmed that the above-mentioned liver function improver has a glutathione-promoting effect and is useful as a liver function improver.

[0125] The total glutathione amount mentioned above can be calculated based on a standard curve of a pre-prepared glutathione standard with known concentrations after the sample is reacted with glutathione reductase, followed by the addition of 5,5'-dithiobis(2-nitrobenzoic acid), and the absorbance at a wavelength of 412 nm after 5 minutes.

[0126] The fact that the ATP production-promoting effect of the aforementioned liver function improver increased the ATP production when the aforementioned liver function improver was added, compared to the ATP production without the addition of the aforementioned liver function improver, confirms that the aforementioned liver function improver has an ATP production-promoting effect and is useful as a liver function improver.

[0127] The above-mentioned ATP levels can be measured using commercially available ATP assay kits (e.g., "cellular" ATP assay kits). TM Ver.2 (manufactured by Toyo B-Net Co., Ltd.) was measured.

[0128] The liver function improver showed that it promoted hepatocyte proliferation, and since the number of hepatocytes increased when the liver function improver was added, it can be confirmed that the liver function improver has a hepatocyte proliferation promoting effect and is useful as a liver function improver.

[0129] The number of hepatocytes mentioned above can be determined by the MTT assay.

[0130] The content of the compound represented by the above general formula (1) in the above-mentioned liver function improver is not particularly limited as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0131] In particular, considering the glutathione-promoting effect of the aforementioned liver function improver, the content of mangiferin in the aforementioned liver function improver relative to the total amount of the aforementioned liver function improver is preferably 6 μmol / L or more, more preferably 25 μmol / L or more, and even more preferably 100 μmol / L or more. Furthermore, considering the glutathione-promoting effect, the content of mangiferin in the aforementioned liver function improver is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0132] Furthermore, considering the ATP-promoting effect of the aforementioned liver function improver, the content of mangiferin in the aforementioned liver function improver relative to the total amount of the aforementioned brain function improver is preferably 1 μmol / L or more, more preferably 6 μmol / L or more, even more preferably 25 μmol / L or more, and particularly preferably 100 μmol / L or more. Additionally, considering the ATP-promoting effect, the content of mangiferin in the aforementioned liver function improver is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0133] Furthermore, considering the hepatocyte proliferation-promoting effect of the aforementioned liver function improver, the content of mangiferin in the aforementioned liver function improver relative to the total amount of the aforementioned brain function improver is preferably 20 μmol / L or more, more preferably 25 μmol / L or more. Additionally, considering the hepatocyte proliferation-promoting effect, the content of mangiferin in the aforementioned liver function improver is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0134] The aforementioned liver function improver can be the compound represented by the general formula (1) above. Furthermore, there is no particular limitation on the content ratio of mangiferin to mangiferin in the aforementioned liver function improver; either one may be contained alone, or both may be contained in an appropriately selected content ratio, with mangiferin being preferred.

[0135] In addition, the present invention also includes a glutathione production promoter containing the compound shown in the above general formula (1) as an active ingredient, an ATP production promoter containing the compound shown in the above general formula (1) as an active ingredient, and a hepatocyte proliferation promoter containing the compound shown in the above general formula (1) as an active ingredient.

[0136] <Bone Strengthening Agent> The compound represented by the following general formula (1), which is an effective component of the bone strengthening agent of the present invention, has a type I collagen production promoting effect, and can be used as an effective component of the above-mentioned bone strengthening agent by utilizing this effect.

[0137] Therefore, the above-mentioned bone strengthening agents have a promoting effect on type I collagen production.

[0138] As mentioned above, type I collagen is a major component of bone. Therefore, promoting the production of type I collagen in bone can strengthen it.

[0139] The compound represented by the above general formula (1) has an excellent promoting effect on type I collagen production and is useful as a bone strengthening agent. This was previously completely unknown and is a new understanding of the inventors.

[0140] When the amount of type I collagen increased after the addition of the bone strengthener compared to the amount of type I collagen before the addition of the bone strengthener, it can be confirmed that the bone strengthener has a type I collagen production promoting effect and is useful as a bone strengthener.

[0141] The amount of type I collagen mentioned above can be determined using a sandwich ELISA method.

[0142] The content of the compound represented by the above general formula (1) in the above-mentioned bone strengthening agent is not particularly limited, as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0143] In particular, considering the promoting effect of the aforementioned bone-strengthening agent on type I collagen production, the content of mangiferin in the aforementioned bone-strengthening agent relative to the total amount of the aforementioned bone-strengthening agent is preferably 6 μmol / L or more, more preferably 25 μmol / L or more. Furthermore, considering the promoting effect on type I collagen production, the content of mangiferin in the aforementioned bone-strengthening agent is preferably high; however, there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0144] The bone-strengthening agent described above can be the compound represented by the general formula (1) above. Furthermore, there is no particular limitation on the ratio of mangiferin to mangiferin in the bone-strengthening agent; either one may be contained alone, or both may be contained in an appropriately selected ratio, with mangiferin being preferred.

[0145] In addition, the present invention also includes a type I collagen production promoter containing a compound represented by the above general formula (1) as an active ingredient.

[0146] <Blood sugar level improver> The compound represented by the following general formula (1), which is the active ingredient of the blood glucose level improver of the present invention, has a dipeptidyl peptidase IV (DPPIV) activity inhibition effect, and can be used as the active ingredient of the above-mentioned blood glucose level improver by utilizing this effect.

[0147] Therefore, the above-mentioned blood glucose improvers have an inhibitory effect on DPPIV activity.

[0148] As described above, DPPIV is an enzyme that inhibits insulin secretion from pancreatic β cells and glucagon secretion from pancreatic α cells, thereby breaking down incretins, a hormone that has effects such as lowering blood pressure. Therefore, by inhibiting the enzymatic activity of DPPIV, it is possible to improve blood glucose levels.

[0149] The compound represented by the above general formula (1) has excellent DPPIV activity inhibition effect and is useful as a blood glucose level improver. This was previously completely unknown and is a new understanding of the inventors.

[0150] Compared to the DPPIV activity of the above-mentioned blood glucose level improver without the addition, the addition of the above-mentioned blood glucose level improver increased the DPPIV activity inhibition, confirming that the above-mentioned blood glucose level improver has a DPPIV activity inhibition effect and is useful as a blood glucose level improver.

[0151] The above-mentioned DPPIV activity can be determined by reacting with incretins such as Gly-Pro-p-NA·Tos[GPNT] solution (manufactured by Peptide Research Institute Co., Ltd.) which serve as the matrix of DPPIV, and by measuring the absorbance of p-NA (p-nitroaniline) free from the matrix.

[0152] The content of the compound represented by the above general formula (1) in the above-mentioned blood glucose level improver is not particularly limited as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0153] In particular, considering the DPPIV activity inhibition effect of the aforementioned blood glucose level improver, the content of mangiferin in the aforementioned blood glucose level improver relative to the total amount of the aforementioned blood glucose level improver is preferably 1 μmol / L or more, more preferably 6 μmol / L or more, even more preferably 25 μmol / L or more, and particularly preferably 100 μmol / L or more. Furthermore, considering the DPPIV activity inhibition effect, the content of mangiferin in the aforementioned blood glucose level improver is preferably high, but there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0154] Furthermore, considering the DPPIV activity inhibition effect of the aforementioned blood glucose level improver, the content of mangiferin in the aforementioned blood glucose level improver relative to the total amount of the aforementioned blood glucose level improver is preferably 1 μmol / L or more, more preferably 6 μmol / L or more, even more preferably 25 μmol / L or more, and particularly preferably 100 μmol / L or more.

[0155] The aforementioned blood glucose level improver can be the compound represented by the general formula (1) above. Furthermore, there is no particular limitation on the content ratio of mangiferin to mangiferin in the aforementioned blood glucose level improver; either one may be contained alone, or both may be contained in an appropriately selected content ratio.

[0156] In addition, the present invention also includes DPPIV activity inhibitors containing compounds of the above general formula (1) as active ingredients.

[0157] Muscle enhancers The compound represented by the following general formula (1), which is an effective component of the muscle enhancer of the present invention, has a myoblast proliferation promoting effect, and can be used as an effective component of the above-mentioned muscle enhancer by utilizing this effect.

[0158] Therefore, the aforementioned muscle enhancers have a myoblast proliferation-promoting effect.

[0159] As described above, myoblasts are the cells that make up muscle. Therefore, by promoting the proliferation of myoblasts in muscle, muscle strengthening can be achieved.

[0160] The compound represented by the above general formula (1) has excellent myoblast proliferation promoting effect and is useful as a muscle enhancer. This was previously completely unknown and is a new understanding of the inventors.

[0161] When the number of myoblasts increased after the addition of the muscle enhancer compared to the number of myoblasts before the addition of the muscle enhancer, it can be confirmed that the muscle enhancer has a myoblast proliferation promoting effect and is useful as a muscle enhancer.

[0162] The number of myoblasts mentioned above can be determined by the MTT assay.

[0163] The content of the compound represented by the above general formula (1) in the above muscle enhancer is not particularly limited, as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0164] In particular, considering the myoblast proliferation-promoting effect of the aforementioned muscle enhancer, the content of the aforementioned mangiferin in the aforementioned muscle enhancer relative to the total amount of the aforementioned muscle enhancer is preferably 1 μmol / L or more, more preferably 1 μmol / L or more and 6 μmol / L or less, and even more preferably 1.5 μmol / L or more and 5 μmol / L or less.

[0165] Furthermore, the aforementioned muscle enhancer can be the compound represented by the general formula (1) itself. Moreover, there is no particular limitation on the ratio of mangiferin to mangiferin in the aforementioned muscle enhancer; either one may be present, or both may be present in an appropriately selected ratio, with mangiferin being preferred.

[0166] In addition, the present invention also includes myoblast proliferation promoters containing compounds of the above general formula (1) as active ingredients.

[0167] -Dosage Form- The compound represented by the above general formula (1) can be formulated into any dosage form, such as powder, granules, or liquid, using pharmaceutically permissible carriers such as dextrin and cyclodextrin, and other arbitrary excipients, according to conventional methods. At this time, excipients, binders, disintegrants, lubricants, stabilizers, flavoring / odorizing agents, etc., can be used as excipients.

[0168] The aforementioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose improvers, and muscle strengtheners can be used in combination with other compositions (e.g., oral compositions, cosmetic compositions, etc., described later), and can also be used as oral administration agents such as tablets, powders, capsules, granules, extracts, and syrups; non-oral administration agents such as injections, drops, and suppositories; and ointments, eye drops, topical liquids, and patches.

[0169] There are no particular restrictions on the use of the above-mentioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose improvers, and muscle strengtheners. They can be appropriately selected according to the purpose. For example, oral, non-oral, and topical use can be mentioned.

[0170] There are no particular restrictions on the dosage forms of the aforementioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose improvers, and muscle strengtheners. They can be appropriately selected according to the purpose. For example, oral administration preparations such as tablets, powders, capsules, granules, extracts, and syrups can be included; non-oral administration preparations such as injections, drops, and suppositories can be included; and external preparations such as lotions, emulsions, creams, ointments, beauty serums, facial masks, gels, lipsticks, lip glosses, foundations, bath preparations, soaps, shower gels, conditioners, hair growth tonics, hair creams, hair lotions, fragrances, shampoos, and rinses can be included.

[0171] The manufacturing methods for the aforementioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose improvers, and muscle strengtheners, which are in any dosage form, are not particularly limited, and known methods can be appropriately selected.

[0172] -Usage and Dosage- There are no particular restrictions on the administration method, dosage, administration site, administration period, and administration interval of the aforementioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose level improvers, and muscle strengtheners; they can be appropriately selected according to the purpose.

[0173] -use- The aforementioned anti-obesity agent, anti-inflammatory agent, brain function improver, liver function improver, bone strengthener, blood glucose improver, and muscle strengthener each possess excellent anti-obesity effects, excellent anti-inflammatory effects, excellent brain function improvement effects, excellent liver function improvement effects, excellent bone strengthening effects, excellent blood glucose improvement effects, and excellent muscle strengthening effects, respectively. They are highly safe and can be used in a wide range of applications, such as pharmaceuticals, quasi-drugs, food products, and cosmetics. For example, they are suitable as active ingredients in oral compositions and cosmetic compositions described later. In this case, the compound represented by the above general formula (1) can be directly combined with at least one of the compounds represented by the above structural formula (1) and the compounds represented by the above structural formula (2). The product formed by formulating at least one of the compounds represented by the above structural formula (1) and the compounds represented by the above structural formula (2) can also be combined with the compound represented by the above general formula (1).

[0174] In addition, the above-mentioned anti-obesity agent, the above-mentioned anti-inflammatory agent, the above-mentioned brain function improver, the above-mentioned liver function improver, the above-mentioned bone strengthener, the above-mentioned blood glucose level improver, and the above-mentioned muscle strengthener can be used as an active ingredient by combining other components having at least one of the effects selected from anti-obesity effect, anti-inflammatory effect, brain function improvement effect, liver function improvement effect, bone strengthening effect, blood glucose level improvement effect, and muscle strengthening effect with the compound shown in the above general formula (1) as needed.

[0175] The aforementioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose level improvers, and muscle strengtheners are suitable for human use, and as long as they exert their respective effects, they can also be used in animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cattle, pigs, monkeys, etc.).

[0176] Furthermore, the aforementioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose improvers, and muscle strengtheners can each be used as reagents in research related to their anti-obesity effects, anti-inflammatory effects, brain function improvement effects, liver function improvement effects, bone strengthening effects, blood glucose improvement effects, or muscle strengthening effects.

[0177] In addition, compounds represented by the above general formula (1) for use in anti-obesity, anti-inflammatory, brain function improvement, liver function improvement, bone strengthening, blood sugar improvement, or muscle strengthening are also included within the scope of this invention.

[0178] Furthermore, the use of compounds represented by the following general formula (1) in the manufacture of pharmaceuticals for anti-obesity, anti-inflammatory, brain function improvement, liver function improvement, bone strengthening, blood sugar improvement, or muscle strengthening is also included within the scope of this invention.

[0179] (Oral composition) The oral composition of the present invention contains at least one selected from the group consisting of the anti-obesity agent of the present invention, the anti-inflammatory agent of the present invention, the brain function improver of the present invention, the liver function improver of the present invention, the bone enhancer of the present invention, the blood glucose improver of the present invention, and the muscle enhancer of the present invention, and may further contain other ingredients as needed.

[0180] <Anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar improvers, and muscle strengtheners> The content of at least one of the above-mentioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose improvers, and muscle strengtheners in the oral composition is not particularly limited and can be appropriately selected according to the purpose. Furthermore, the content of at least one of the above-mentioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood glucose improvers, and muscle strengtheners is preferably higher, but there is no particular upper limit, and it can be appropriately selected according to the purpose.

[0181] <Other Ingredients> The oral composition described above may further contain other ingredients commonly used in the manufacture of oral compositions, as needed and without prejudice to the purpose and effects of the present invention.

[0182] <<Other Ingredients>> The other components in the above-mentioned oral composition are not particularly limited and can be appropriately selected according to the purpose. Examples include excipients, moisture-proofing agents, preservatives, reinforcing agents, thickeners, emulsifiers, antioxidants, sweeteners, acidulants, flavorings, colorants, fragrances, whitening agents, moisturizers, oily components, ultraviolet absorbers, surfactants, thickeners, alcohols, powder components, colorants, aqueous components, and water. They can be used alone or in combination with two or more. When these components are used in combination with at least one selected from the group consisting of the above-mentioned anti-obesity agents, the above-mentioned anti-inflammatory agents, the above-mentioned brain function improvers, the above-mentioned liver function improvers, the above-mentioned bone strengtheners, the above-mentioned blood glucose improvers, and the above-mentioned muscle strengtheners, they sometimes act synergistically to exert the superior effects generally expected above.

[0183] The content of the other components in the oral composition described above is not particularly limited, as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0184] -use- Examples of the aforementioned oral compositions include, for instance, oral administration agents and food products. Here, food products refer to substances that pose little risk to human health, are ingested orally or through the digestive tract in normal daily life, and are not subject to administrative categorization as food, medicine, quasi-drugs, etc. Therefore, the aforementioned food products broadly encompass those constituting orally ingested general foods, health foods (functional food products), health function foods (foods for specific health purposes, nutritional function foods, functional display foods), quasi-drugs, and medicines.

[0185] There are no particular limitations on the types of oral compositions mentioned above, and they can be appropriately selected according to the purpose. Examples include beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, alcoholic drinks, coffee drinks, and caffeinated soft drinks (containing concentrated stock solutions and conditioning powders); frozen treats such as ice cream, shaved ice, and ice cream; noodles such as buckwheat noodles, udon noodles, rice noodles, dumpling wrappers, shumai wrappers, Chinese noodles, and instant noodles; sweets such as sugar, candy, chewing gum, chocolate, candy sheets, bagged snacks, biscuits, jelly, jam, cream, baked goods, and bread; seafood such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oysters, saury, squid, cockles, scallops, abalone, sea urchin, salmon roe, and baby abalone; fish cakes, ham, etc. Processed aquatic and livestock products such as sausages; dairy products such as processed milk and fermented milk; oils and oil-based processed products such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and sauces; seasonings such as sauces and condiments; steamed and boiled foods such as curry, stews, chicken and egg rice bowls, porridge, mixed porridge, Chinese rice bowls, fried pork chop rice bowls, tempura rice bowls, eel rice bowls, beef stew rice bowls, oden, mapo tofu, beef rice bowls, meat sauce, egg drop soup, omelet rice, dumplings, shumai, hamburgers, and meatballs; home-style dishes such as salads and pickles; various forms of health, beauty, and nutritional supplements; pharmaceuticals and quasi-drugs such as tablets, powders, capsules, granules, extracts, syrups, beverages, lozenges, and mouthwashes; oral cooling agents, halitosis prevention agents, and toothpaste for oral use.

[0186] There are no particular limitations on the method for manufacturing the above-mentioned oral composition, and a suitable method can be selected from known methods depending on the type of the oral composition.

[0187] There are no particular restrictions on the amount, duration, or interval of use of the above-mentioned oral composition, and it can be appropriately selected according to the purpose.

[0188] The oral composition of the present invention is suitable for human use, and, provided that each of its respective effects is achieved, it is also suitable for animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cattle, pigs, monkeys, etc.).

[0189] The oral composition of the present invention contains at least one selected from the group consisting of the above-mentioned anti-obesity agent, the above-mentioned anti-inflammatory agent, the above-mentioned brain function improver, the above-mentioned liver function improver, the above-mentioned bone strengthening agent, the above-mentioned blood glucose level improver, and the above-mentioned muscle strengthening agent. Therefore, when administered orally, each of these components is useful in exerting an effect selected from the group consisting of excellent anti-obesity effect, excellent anti-inflammatory effect, excellent brain function improvement effect, excellent liver function improvement effect, excellent bone strengthening effect, excellent blood glucose level improvement effect, and excellent muscle strengthening effect.

[0190] (Cosmetic composition) The cosmetic composition of the present invention contains at least one selected from the group consisting of the anti-obesity agent of the present invention, the anti-inflammatory agent of the present invention, the brain function improver of the present invention, the liver function improver of the present invention, the bone enhancer of the present invention, the blood glucose improver of the present invention, and the muscle enhancer of the present invention, and may further contain other ingredients as needed.

[0191] <Anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar improvers, and muscle strengtheners> The content of at least one of the above-mentioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar improvers, and muscle strengtheners in the cosmetic composition is not particularly limited and can be appropriately selected according to the purpose. Furthermore, the content of at least one of the above-mentioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar improvers, and muscle strengtheners is preferably higher, but there is no particular upper limit, and it can be appropriately selected according to the purpose. In addition, the cosmetic composition may be at least one of the above-mentioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar improvers, and muscle strengtheners.

[0192] <Other Ingredients> The above-described cosmetic composition may further contain, as needed and without prejudice to the purpose and effect of the present invention, various main agents, auxiliary agents, and other ingredients commonly used in the manufacture of cosmetic compositions.

[0193] The other ingredients in the above-mentioned cosmetic composition are not particularly limited and can be appropriately selected according to the purpose. Examples include astringents, bactericides, antibacterial agents, ultraviolet absorbers, cell activators, oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, and fragrances. They can be used alone or in combination with two or more. When these ingredients are used in combination with at least one selected from the group consisting of the above-mentioned anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar improvers, and muscle strengtheners, they sometimes act synergistically to exert the superior effects generally expected above.

[0194] The content of the other ingredients in the above-described cosmetic composition is not particularly limited, as long as it does not impair the effect of the present invention, and can be appropriately selected according to the purpose.

[0195] -use- There are no particular limitations on the uses of the above-mentioned cosmetic compositions, and appropriate choices can be made from general uses of cosmetic compositions. For example, skin cosmetic compositions such as lotions, emulsions, creams, ointments, beauty serums, facial masks, gels, lipsticks, lip glosses, foundations, bath preparations, soaps, and shower gels can be used; scalp and hair cosmetic compositions such as conditioners, hair growth tonics, hair creams, hair lotions, fragrances, shampoos, and rinses can also be used.

[0196] The cosmetic composition described above may incorporate at least one of the following selected ingredients—the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthener, the blood sugar improver, and the muscle strengthener—in any cosmetic composition in a manner that does not impair their activity. It may be a cosmetic composition in which at least one of the following selected ingredients—the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthener, the blood sugar improver, and the muscle strengthener—is used as the main ingredient.

[0197] There are no particular limitations on the manufacturing method of the above-mentioned cosmetic composition, and a suitable method can be selected from known methods depending on the type of cosmetic composition.

[0198] There are no particular restrictions on the amount, duration, or interval of use of the above-mentioned cosmetic composition, and it can be appropriately selected according to the purpose.

[0199] The cosmetic composition of the present invention is suitable for human use, and can also be used on animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cattle, pigs, monkeys, etc.) as long as they exert their respective effects.

[0200] The cosmetic composition of the present invention contains at least one selected from the group consisting of the above-mentioned anti-obesity agent, the above-mentioned anti-inflammatory agent, the above-mentioned brain function improver, the above-mentioned liver function improver, the above-mentioned bone strengthening agent, the above-mentioned blood glucose level improver, and the above-mentioned muscle strengthening agent. Therefore, when applied to the skin, each of them is useful in exerting an effect of at least one selected from the group consisting of excellent anti-obesity effect, excellent anti-inflammatory effect, excellent brain function improvement effect, excellent liver function improvement effect, excellent bone strengthening effect, excellent blood glucose level improvement effect, and excellent muscle strengthening effect.

[0201] Example The following examples illustrate the invention in detail, but the invention is not limited by these examples.

[0202] (Experiment 1: Test on the inhibition of α-glucosidase activity) -Preparation of the test sample solution- The mangiferin used as the test sample was a solution of M3547 (batch number: SLBQ6689V, manufactured by SIGMA) dissolved in dimethyl sulfoxide (DMSO).

[0203] In addition, the mangiferin used as the test sample was a solution of ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) dissolved in DMSO.

[0204] -Preparation of crude enzyme solution- As an α-glucosidase, 1 g of rat-derived intestinal acetone powder (I1630 SIGMA) was suspended in 10 mL of 0.1 mol / L phosphate buffer (pH 7.0) (hereinafter sometimes referred to as "PB"). After stirring at 4°C for 1 hour, the mixture was centrifuged at 3,500 rpm for 15 minutes and the resulting supernatant was used as the crude enzyme solution.

[0205] -Determination of the test sample solution- Add 65 μL of PB solution, 30 μL of crude enzyme solution, and 5 μL of test sample solution to a 48-well plate. Additionally, add the test sample solution to achieve the final concentrations shown in Tables 1 and 2 below. Add 400 μL of 10 mmol / L maltose PB solution or 20 mmol / L sucrose PB solution as a matrix, and incubate at 37°C for 30 minutes. After the reaction, stop the reaction by immersion in boiling water for 2 minutes. After cooling with ice, determine the amount of glucose produced by decomposition using a glucose CII-Testwako (manufactured by Fujifilm and Koko Pure Chemical Industries, Ltd.).

[0206] -Determination of the blank in the test sample solution- In the determination of the test sample solution, 400 μL of matrix was not added. Instead, 400 μL of PB solution was added. Otherwise, the glucose content was determined using the same method as in the determination of the test sample solution.

[0207] -Determination of the control solution- In the determination of the test sample solution, 5 μL of the test sample solution was not added, but 5 μL of DMSO was added. Otherwise, the glucose content was determined using the same method as the determination of the test sample solution.

[0208] -Determination of blank control solution- In the determination of the test sample solution, 5 μL of the test sample solution was not added, 5 μL of DMSO was added, and 400 μL of the matrix was not added. Instead of the matrix, 400 μL of PB solution was added. Otherwise, the glucose content was determined using the same method as the determination of the test sample solution.

[0209] Calculation of the inhibition rate of α-glucosidase activity- Based on the measured values ​​obtained by measuring the test sample solution, measuring the test sample solution blank, measuring the control solution, and measuring the control solution blank, the α-glucosidase activity inhibition rate is calculated using the following formula (1).

[0210] α-glucosidase activity inhibition rate (%) = {1 - (AB) / (CD)} × 100 Equation (1) In the above formula (1), “A”, “B”, “C” and “D” are respectively as follows: A: The amount of glucose in the test sample solution (both the test sample and the matrix). B: Glucose content in the blank test sample solution (test sample with or without matrix addition). C: Glucose content in the control solution (test sample with no additives and sample with matrix additives). D: Glucose content in the control solution blank (test sample without additives and matrix without additives). <Results> α-Glucosidase is an enzyme with maltase activity that breaks down maltose into glucose and sucrase activity that breaks down sucrose into glucose. The inhibition rate of α-glucosidase (maltase) activity when maltose is used as a substrate is shown in Table 1 below, and the inhibition rate of α-glucosidase (sucrase) activity when sucrose is used as a substrate is shown in Table 2 below.

[0211] Mangiferin was found to inhibit both maltase and sucrase activity. Furthermore, mangiferin was found to inhibit sucrase activity.

[0212] [Table 1] [Table 2] (Experiment 2: Lipase Activity Inhibition Test) <Experimental Methods> The assay for inhibiting the activity of porcine pancreatic lipase was performed using the Lipase Activity Assay Kit S (manufactured by Sumitomo Phenolic Resin Co., Ltd.) and the following method was employed.

[0213] -Preparation of the test sample solution- The mangiferin used as the test sample was a solution of M3547 (batch number: SLBQ6689V, manufactured by SIGMA) dissolved in PBS(-).

[0214] In addition, the mangiferin used as the test sample was a solution of ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) dissolved in PBS(-).

[0215] -Preparation of lipase solution- The lipase solution was prepared by dissolving porcine pancreatic lipase (manufactured by SIGMA) in PBS (-) at a concentration of 0.03 mg / mL.

[0216] -Determination of the test sample solution- Add 10 μL of the test sample solution, 250 μL of the chromogenic solution, 10 μL of the lipase solution, and 5 μL of the esterase inhibitor to a 48-well plate. After pre-incubation at 30°C under darkness for 5 minutes, add 25 μL of the matrix solution to start the reaction. The test sample solution is added to the final concentrations shown in Table 3 below. After reacting at 30°C under darkness for 30 minutes, add 500 μL of the reaction stop solution to stop the reaction. After the reaction stops, measure the absorbance at a wavelength of 412 nm.

[0217] -Determination of the blank in the test sample solution- Add 10 μL of the test sample solution, 250 μL of the chromogenic solution, 10 μL of the lipase solution, and 5 μL of the esterase inhibitor to a 48-well plate, and pre-incubate at 30°C in the dark for 5 minutes. The test sample solution is added to the final concentrations shown in Table 3 below. After reacting at 30°C in the dark for 30 minutes, add 500 μL of reaction stop solution to stop the reaction. After the reaction stops, add 25 μL of matrix solution and measure the absorbance at a wavelength of 412 nm.

[0218] -Determination of the control solution- In the determination of the test sample solution, 10 μL of the test sample solution was changed to 10 μL of PBS(-). Otherwise, the determination was carried out in the same way as the determination of the test sample solution.

[0219] -Determination of blank control solution- Add 10 μL of PBS(-), 250 μL of chromogenic solution, 10 μL of lipase solution, and 5 μL of esterase inhibitor to a 48-well plate, and pre-incubate at 30°C in the dark for 5 minutes. After reacting at 30°C in the dark for 30 minutes, add 500 μL of reaction stop solution to stop the reaction. After the reaction stops, add 25 μL of matrix solution and measure the absorbance at a wavelength of 412 nm.

[0220] -Calculation of lipase activity inhibition rate- Based on the absorbance obtained by measuring the test sample solution, measuring the test sample solution blank, measuring the control solution, and measuring the control solution blank, the lipase activity inhibition rate is calculated using the following formula (2).

[0221] Lipase activity inhibition rate (%) = {1 - (AB) / (CD)} × 100 Equation (2) In the above formula (2), “A”, “B”, “C”, and “D” are as follows: A: Absorbance of the test sample solution (both the test sample and the matrix) at a wavelength of 412 nm. B: Absorbance of the blank test sample solution (test sample added and matrix added after the reaction was stopped) at a wavelength of 412 nm. C: Absorbance of the control solution (test sample with no additives and no matrix additives) at a wavelength of 412 nm. D: Absorbance at 412 nm for the control solution blank (sample without additives and sample with matrix added after reaction cessation). <Results> The lipase activity inhibition rates are shown in Table 3 below. Both mangiferin and mangiferin were confirmed to inhibit lipase activity.

[0222] [Table 3] (Experiment 3: Inhibition of Aminohexosidase) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was a solution in which M3547 (batch number: SLBQ6689V, manufactured by SIGMA) was dissolved in a silica (Siraganian) buffer (pH 7.2).

[0223] In addition, the mangiferin used as the test sample was a solution in which ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) was dissolved in silica buffer (pH 7.2).

[0224] In addition, the silica buffer was prepared by mixing 119 mM NaCl, 5 mM KCl, 0.4 mM MgCl2, 1 mM CaCl2, 40 mM NaOH, 25 mM PIPES, 5.6 mM glucose, and 0.1 volume % BSA.

[0225] -Preculture of rat basophilic leukemia cells- Rat basophilic leukemia cells (RBL-2H3) were cultured in S-MEM (prepared by GIBCO) containing 15% fetal bovine serum (FBS) and then recovered by trypsin treatment. The recovered cells were cultured to a density of 4.0 × 10⁶ cells / mL. 5 Cells were diluted using S-MEM containing 15% FBS to achieve a final concentration of 0.5 μg / mL for DNP-specific IgE (SIGMA). 100 μL was then seeded into each well of a 96-well plate and incubated overnight at 37°C with 5% CO2. After incubation, the culture medium was removed, and the cells were washed twice with 100 μL of silica buffer.

[0226] -Determination of the test sample solution- To each well of pre-cultured, washed rat basophilic leukemia cells (RBL-2H3), 30 μL of silica buffer and 10 μL of the test sample solution were added to achieve the final concentrations shown in Table 4 below, and the plates were incubated at 37°C for 10 minutes. Then, 10 μL of DNP-BSA solution diluted with silica buffer was added to achieve a DNP-BSA concentration of 400 ng / mL, and the plates were incubated at 37°C for 15 minutes to release the aminohexosidase. The 96-well plates were then placed on ice to stop the release of the aminohexosidase. 10 μL of cell supernatant from each well and 10 μL of p-NAG solution diluted with 0.1 mol / L citrate buffer to achieve a p-nitrophenyl N-acetyl β-D-glucosamine (p-NAG) concentration of 1 mmol / L were added to a new 96-well plate, and the plates were incubated at 37°C for 1 hour. After the reaction was completed, 250 μL of a 0.1 mol / L Na2CO3 / NaHCO3 mixed aqueous solution was added to each well, and the absorbance at wavelengths of 415 nm and 650 nm was measured. The absorbance at wavelength 415 nm was then subtracted from the absorbance at wavelength 650 nm.

[0227] -Determination of the blank in the test sample solution- In the determination of the test sample solution, 10 μL of p-NAG solution was not added. Instead, 10 μL of citrate buffer was added. Otherwise, the absorbance at wavelengths of 415 nm and 650 nm was measured using the same method as the determination of the test sample solution. The absorbance at wavelength 415 nm was calculated by subtracting the absorbance at wavelength 650 nm from the absorbance at wavelength 415 nm.

[0228] -Determination of the control solution- In the determination of the test sample solution, 10 μL of the test sample solution was not added. Instead, 10 μL of silica buffer solution was added. Otherwise, the absorbance at wavelengths of 415 nm and 650 nm was measured using the same method as the determination of the test sample solution. The value obtained by subtracting the absorbance at wavelength 650 nm from the absorbance at wavelength 415 nm was calculated.

[0229] -Determination of blank control solution- In the determination of the test sample solution, 10 μL of the test sample solution and 10 μL of p-NAG solution were not added. Instead, 10 μL of silica buffer was added, and instead of p-NAG solution, 10 μL of 0.1M citrate buffer was added. Otherwise, the absorbance at wavelengths of 415 nm and 650 nm was measured using the same method as the determination of the test sample solution. The absorbance at wavelength 415 nm was calculated by subtracting the absorbance at wavelength 650 nm from the absorbance at wavelength 415 nm.

[0230] -Calculation of the free inhibition rate of aminohexosidase- Based on the absorbance difference [(absorbance at wavelength 415 nm) - (absorbance at wavelength 650 nm)] obtained by measuring the test sample solution, test sample solution blank, control solution, and control solution blank, the free inhibition rate of aminohexosidase is calculated by the following formula (3).

[0231] The free inhibition rate of aminohexosidase (%) = {1 - (AB) / (CD)} × 100 Equation (3) In the above formula (3), “A” and “B” are as follows: A: Absorbance difference between the test sample solution (with added test sample and with added p-NAG) [(Absorbance at 415 nm) - (Absorbance at 650 nm)] B: Absorbance difference between the blank test sample solution (test sample with added p-NAG and test sample without added p-NAG) [(Absorbance at 415 nm) - (Absorbance at 650 nm)] C: Absorbance difference between the control solution (test sample with no additive and p-NAG additive) [(Absorbance at 415 nm) - (Absorbance at 650 nm)] D: Absorbance difference between the control solution blank (test sample without additive and p-NAG without additive) [(Absorbance at 415 nm) - (Absorbance at 650 nm)] <Results> The free inhibition rate of aminohexosidase is shown in Table 4 below. Mangiferin confirmed a strong inhibitory effect on free aminohexosidase.

[0232] [Table 4] (Experiment 4: PGE2 production inhibition test) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was a solution in which M3547 (batch number: SLBQ6689V, manufactured by SIGMA) was dissolved in DMEM (manufactured by Nissui Pharmaceutical Co., Ltd., the same substance was used in the following test examples) containing 10% by volume FBS.

[0233] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS.

[0234] -Preculture of mouse macrophages- Mouse macrophages (RAW264.7) (obtained from DS Pharmace Biomedical) were cultured in DMEM containing 10% FBS and then recovered using a cell scraper. The recovered cells were spaced to approximately 2.0 × 10⁶ cells per cell volume. 5 Cells were diluted using DMEM containing 10% FBS and seeded at a concentration of 100 μL per well in a 96-well plate. The plates were then incubated at 37°C and 5% CO2 for 18 hours. After incubation, existing COX-1 and a small amount of COX-2 were acetylated to inactivate them. Then, 100 μL of DMEM containing 500 μmol / L aspirin was added, and the plates were incubated at 37°C and 5% CO2 for 4 hours. The cells were then washed three times with PBS(-).

[0235] -Determination of the test sample solution- Pre-cultured, washed mouse macrophages (RAW264.7) were added to each well with 100 μL of the test solution to achieve the final concentration shown in Table 5 below. Then, 100 μL of lipopolysaccharide (LPS, E. coli O111; B4, DIFCO) dissolved in DMEM containing 10 v / mL FBS was added. The cells were incubated at 37°C and 5% CO2 for 16 hours. After incubation, the amount of prostaglandin E2 in the culture supernatant of each well was quantified using the PGE2 EIA Kit (Cayman Chemical).

[0236] -Control (with LPS stimulation) assay- In the determination of the test sample solution, 100 μL of the test sample solution was changed to 100 μL of DMEM containing 10% FBS by volume. Otherwise, the blank of the test sample solution was determined in the same way as the test sample solution.

[0237] -Control (without LPS stimulation) assay- In the determination of the test sample solution, 100 μL of the test sample solution and 100 μL of lipopolysaccharide with a final concentration of 1 μg / mL dissolved in DMEM containing 10% FBS were changed to 200 μL of DMEM containing 10% FBS. Otherwise, the control solution was determined in the same way as the test sample solution.

[0238] -Calculation of the inhibition rate of PGE2- Based on the quantitative values ​​obtained by measuring the test sample solution, measuring the test sample solution blank, and measuring the control solution, the PGE2 inhibition rate is calculated using the following formula (4).

[0239] PGE2 inhibition rate (%) = {1 - (AC) / (BC)} × 100 Equation (4) In the above formula (4), “A”, “B”, and “C” are as follows: A: The amount of prostaglandin E2 in the test sample solution (when the test sample was added and when stimulated by LPS). B: Prostaglandin E2 levels in the control group (with LPS stimulation) (without LPS stimulation or addition to the test sample) C: Prostaglandin E2 levels in the control group (without LPS stimulation) (when the test sample was neither added nor stimulated by LPS) <Results> The PGE2 production inhibition rates are shown in Table 5 below. Mangiferin was confirmed to have an extremely strong inhibitory effect on PGE2 production. In addition, mangiferin was confirmed to have a weak inhibitory effect on PGE2 production.

[0240] [Table 5] (Experiment 5: Assay on the Promoting Effect of Astrocytes on Proliferation) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume of FBS.

[0241] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS.

[0242] -Preculture of mouse-derived astrocyte culture lines- Mouse-derived astrocyte culture (C8-S) (obtained from ATCC) was cultured in DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were cultured to a density of 2.5 × 10⁶ cells / mL. 4 Cell concentrations were diluted with DMEM containing 10% FBS and 100 μL were seeded into each well of a 96-well plate. The plates were then incubated at 37°C and 5% CO2 for 6 hours.

[0243] -Determination of the test sample solution- 100 μL of the test sample solution was added to each well of the pre-cultured mouse-derived astrocyte culture (C8-S) to achieve the final concentration shown in Table 6 below, and the cells were cultured at 37°C and 5% CO2 for 4 days. Cell proliferation promotion was measured using the MTT assay. After culture, the culture medium was removed, and 100 μL of MTT (prepared by Dojin Chemical Research Institute) at a final concentration of 0.4 mg / mL dissolved in PBS(-) was added to each well. After culturing at 37°C and 5% CO2 for 2 hours, the blue formazan generated within the cells was extracted using 100 μL of 2-propanol. The absorbance at 570 nm was measured after extraction. Simultaneously, the absorbance at 650 nm was measured as turbidity, and the amount of blue formazan generated was obtained based on the difference between the two (absorbance at 570 nm - absorbance at 650 nm).

[0244] -Determination of the control solution- In the determination of the test sample solution, 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 10% FBS by volume. Otherwise, the control solution was determined using the same method as the test sample solution.

[0245] -Calculation of the astrocyte proliferation promotion rate- Based on the amount of blue scab produced by measuring the test sample solution and the control solution, the astrocyte proliferation promotion rate is calculated using the following formula (5).

[0246] Astrocyte proliferation promotion rate (%) = A / B × 100 Equation (5) In the above formula (5), “A” and “B” are as follows: A: The amount of blue formazan produced in cells of the test sample solution (when the test sample was added). B: Blue formazan production in cells of the control solution (without additives to the test sample). <Results> The astrocyte proliferation promotion rate is shown in Table 6 below. Both mangiferin and mangiferin were confirmed to have a significant astrocyte proliferation promotion effect.

[0247] [Table 6] (Experiment 6: Assay on the promoting effect of AQP4 mRNA expression in astrocytes) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume FBS.

[0248] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS.

[0249] -Preculture of mouse-derived astrocyte culture lines- Mouse-derived astrocyte culture (C8-S) (obtained from ATCC) was cultured in DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were then cultured to a density of 5.0 × 10⁶ cells / mL. 4 The cell / mL concentration was diluted with DMEM containing 10% FBS by volume, and 2 mL was seeded into each well of a 6-well plate. The plates were then incubated at 37°C and 5% CO2 until the plates were fully covered.

[0250] -Determination of the test sample solution- After pre-culture, the culture medium was removed from each well of the pre-cultured mouse-derived astrocyte culture (C8-S), and 2 mL of the test sample solution was added to each well at the final concentration shown in Table 7 below. The cells were then incubated at 37°C and 5% CO2 for 24 hours. After incubation, the culture medium was removed, and total RNA was extracted using the RNeasy Mini Kit (Qiagen). The RNA concentration was calculated from the absorbance at 260 nm to obtain a modulated total RNA concentration of 100 ng / μL. This total RNA was used as a template to determine the expression levels of aquaporin 4 (AQP4) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal standard. Detection was performed using a real-time PCR device (Thermal Cycler Dice Real-Time System III, Takara Bio Co., Ltd.) using PrimeScript. TM The reaction was performed using a two-step real-time PCR (RT-PCR) reaction with RT Master Mix (Perfect Real Time, manufactured by Takara Bio Co., Ltd.) and TB Green (registered trademark) Fast qPCR Mix (manufactured by Takara Bio Co., Ltd.).

[0251] -Determination of the control solution- In the determination of the test sample solution, 2 mL of the test sample solution was replaced with 2 mL of DMEM containing 10% FBS by volume. Otherwise, the control solution was determined in the same way as the test sample solution.

[0252] Calculation of the AQP4 mRNA expression promotion rate- The expression level of AQP4 mRNA obtained by measuring the test sample solution and the control solution was corrected by measuring the expression level of GAPDH mRNA obtained by measuring them separately. The expression promotion rate of AQP4 mRNA was calculated using the following formula (6).

[0253] AQP4 mRNA expression promotion rate (%) = A / B × 100 (6) In the above formula (6), “A” and “B” are as follows: A: Corrected value derived from the expression level of AQP4 mRNA and GAPDH mRNA in the test sample solution (when the test sample is added). B: Correction value derived from the expression level of AQP4 mRNA and GAPDH mRNA in the control solution (without additives in the test sample). <Results> The AQP4 mRNA expression promotion rate is shown in Table 7 below. As shown in Table 7 below, both mangiferin and mangiferin confirmed a significant AQP4 mRNA expression promotion effect.

[0254] [Table 7] (Experiment 7: Inhibition of tumor necrosis factor-α (TNF-α) production in microglia) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume FBS.

[0255] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS.

[0256] -Pre-culture of mouse-derived microglial culture lines- Mouse-derived microglial cell line (C8-B4) (obtained from ATCC) was cultured in DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were cultured to a density of 1.0 × 10⁶ cells / mL. 5 The cell / mL concentration was diluted with DME M containing 10% FBS by volume, and 100 μL was seeded into each well of a 96-well plate. The plates were then incubated at 37°C and 5% CO2 until confluence.

[0257] -Determination of the test sample solution- After the pre-culture was completed, the culture medium was removed from each well of the pre-cultured mouse-derived microglial culture (C8-B4), and 100 μL of the test sample solution was added to each well at the final concentration shown in Table 8 below. Then, 100 μL of a mixture of lipopolysaccharide (LPS, E. coli O111; B4, SIGMA) dissolved in DMEM containing 10% FBS at a final concentration of 0.5 μg / mL and interferon-gamma (IFN-γ from mice, R&D Systems) at 5 ng / mL was added, and the mixture was incubated at 37°C and 5% CO2 for 24 hours. After the culture was completed, the amount of TNF-α in the culture supernatant of each well was determined by a sandwich ELISA method using anti-Mouse TNF-α monoclonal antibody (Anti-Mouse TNF-α monoclonal Ab (MM350C), manufactured by Thermo Fisher Scientific) and anti-Mouse TNF-α polyclonal antibody (Anti-Mouse TNF-α polyclonal Ab (P350), manufactured by Thermo Fisher Scientific).

[0258] -Determination of the control solution- In the determination of the test sample solution, 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 10% FBS by volume. Otherwise, the control solution was determined using the same method as the test sample solution.

[0259] -Calculation of the inhibition rate of TNF-α production- Based on the amount of TNF-α obtained by measuring the test sample solution and the control solution, the inhibition rate of TNF-α production is calculated using the following formula (7).

[0260] TNF-α production inhibition rate (%) = {(BA) / B} × 100 Equation (7) In the above formula (7), “A” and “B” are as follows: A: The amount of TNF-α in the test sample solution (when the test sample was added). B: TNF-α levels in the control solution (without additives in the test sample). <Results> The inhibition rate of TNF-α production is shown in Table 8 below. As shown in Table 8 below, mangiferin confirmed a significant inhibitory effect on TNF-α production.

[0261] [Table 8] (Experiment 8: Assay on the effect of increased mRNA expression of inflammation-related genes in microglia) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume FBS.

[0262] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS.

[0263] -Pre-culture of mouse-derived microglial culture lines- Mouse-derived microglial cell line (C8-B4) (obtained from ATCC) was cultured in DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were cultured to a density of 1.0 × 10⁶ cells / mL. 5 The cell / mL concentration was diluted with DMEM containing 10% FBS by volume, and 2 mL was seeded into each well of a 6-well plate. The plates were then incubated at 37°C and 5% CO2 until the plates were fully covered.

[0264] -Determination of the test sample solution- After pre-culture, the culture medium was removed from each well of the pre-cultured mouse-derived microglial culture (C8-B4). 1 mL of the test sample solution was added to each well at the final concentration shown in Table 9 below. Then, 1 mL of a mixture containing 0.5 μg / mL lipopolysaccharide (LPS, E. coli O111; B4, SIGMA) dissolved in DMEM containing 10% FBS and 5 ng / mL interferon-gamma (mouse IFN-γ, R&D Systems) was added. The mixture was incubated at 37°C and 5% CO2 for 24 hours. After incubation, the culture medium was removed, and total RNA was extracted using RNA extraction reagent (ISOGEN II, ISOGEN II). The RNA amount was calculated from the absorbance at 260 nm to obtain a modulated total RNA concentration of 100 ng / μL. Using this total RNA as a template, the expression levels of mRNA from various inflammation-related genes, including TNF-α, iNOS, IL-6, IL-1β, IL-12, CXCL2, IL-10, and IL-18, as well as GAPDH as an internal standard, were measured. Detection was performed using a real-time PCR device (Thermal Cycler Dice Real-Time System III, manufactured by Takara Bio Co., Ltd.) utilizing PrimeScript. TMThe reaction was performed using a two-step RT-PCR reaction with RT Master Mix (Perfect Real Time, manufactured by Takara Bio Co., Ltd.) and TB Green (registered trademark) Fast qPCR Mix (manufactured by Takara Bio Co., Ltd.).

[0265] -Determination of the control solution- In the determination of the test sample solution, 1 mL of the test sample solution was replaced with 1 mL of DMEM containing 10% FBS by volume. Otherwise, the control solution was determined using the same method as the test sample solution.

[0266] -Determination of the unstimulated control solution- In the determination of the test sample solution, 1 mL of the test sample solution was replaced with 1 mL of DMEM containing 10% FBS by volume, and 1 mL of the mixture of LPS and IFN-γ was replaced with 1 mL of DMEM containing 10% FBS by volume. Otherwise, the determination of the unstimulated control solution was carried out in the same way as the determination of the test sample solution.

[0267] -Calculation of mRNA expression rates of inflammation-related genes- The expression levels of various inflammation-related genes mRNA obtained by measuring the test sample solution, the control solution, and the unstimulated control solution were corrected by the expression level of GAPDH mRNA obtained by measuring them separately, and the mRNA expression rate of various inflammation-related genes was calculated using the following formula (8).

[0268] Expression rate (%) of various inflammation-related genes mRNA = A / B × 100 (Equation 8) In the above formula (8), “A” and “B” are as follows: A: Corrected values ​​for the expression levels of various inflammation-related gene mRNAs in the test sample solution (with test sample added, LPS and IFN-γ stimulation) or the unstimulated control solution (without test sample added, LPS and IFN-γ unstimulated) based on the expression level of GAPDH mRNA. B: Corrected values ​​for the expression levels of various inflammation-related gene mRNAs in the control solution (without additives to the test sample, and without LPS and IFN-γ stimulation) based on the expression level of GAPDH mRNA. <Results> The inhibition rate of TNF-α production is shown in Tables 9 to 11 below. As shown in Tables 9 to 11 below, when comparing the blank with the control, due to stimulation by LPS and IFN-γ, the mRNA expression of TNF-α, iNOS, IL-6, IL-1β, IL-12, and CXCL2, which are inflammation-inducing factors, increased, the mRNA expression of IL-10, which is an inflammation-suppressing factor, decreased, and the mRNA expression of IL-18, which is a member of the IL-1 family, remained unchanged.

[0269] In contrast, it was confirmed that mangiferin reduced the mRNA expression of TNF-α, iNOS, IL-6, IL-1β, and CXCL2, which are inflammatory inducing factors, but also reduced the mRNA expression of IL-10, which is an inflammatory suppressor, and reduced the mRNA expression of IL-18.

[0270] Mangiferin decreases the concentration-dependent mRNA expression of TNF-α, iNOS, IL-6, IL-1β, and CXCL2, which are inflammatory inducing factors, while increasing the mRNA expression of IL-10, which is an inflammatory suppressor, and also increases the mRNA expression of IL-18.

[0271] [Table 9] [Table 10] [Table 11] (Experiment 9: Glutathione production promotion experiment) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 1 volume % FBS.

[0272] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 1 volume % FBS.

[0273] -Pre-culture of normal human hepatocytes- Normal human hepatocytes (obtained from DS Pharmace Biomedical) were cultured in DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were cultured to a density of 1.0 × 10⁶ cells / mL. 5Cells / mL were diluted with DMEM containing 10% FBS and seeded in 200 μL per well of a 48-well plate, and cultured overnight at 37°C and 5% CO2.

[0274] -Determination of the test sample solution- After the initial culture, 200 μL of the test sample was added to each well as shown in Table 12 below as the final concentration, and then incubated at 37°C and 5% CO2 for 24 hours. After the culture, the culture medium was removed from each well, and the sample was washed with 400 μL of PBS(-) and then extracted using protein extraction reagent (M-PER). TM 150 μL of Mammalian Protein Extraction Reagent (ThermoFisher Scientific) was used to extract proteins from cells. 100 μL of this protein extract was used for total glutathione quantification. Specifically, 50 μL of PB, 25 μL of 2 mmol / L NADPH (Fujifilm Kazuki Pure Chemicals Co., Ltd.), and 25 μL of 3.2 units / mL glutathione reductase (SIGMA) were added to 100 μL of the protein extract dissolved in a 96-well plate. After heating at 37°C for 10 minutes, 25 μL of 10 mmol / L 5,5'-dithiobis(2-nitrobenzoic acid) was added, and the absorbance at 412 nm after 5 minutes was measured to determine the OD / min. The total glutathione amount was calculated using oxidized glutathione (Fujifilm Kazuki Pure Chemicals Co., Ltd.) based on a prepared standard curve.

[0275] -Determination of the control solution- In the determination of the test sample solution, the 200 μL of the test sample was replaced with 200 μL of DMEM containing 10% FBS by volume. Otherwise, the control solution was determined using the same method as the test sample solution.

[0276] -Calculation of the glutathione production promotion rate- Based on the total glutathione amount obtained by measuring the test sample solution and the control solution, the glutathione production promotion rate is calculated using the following formula (9).

[0277] Glutathione production promotion rate (%) = A / B × 100 Equation (9) In the above formula (9), “A” and “B” are as follows: A: The amount of glutathione in the cells of the test sample solution (when the test sample is added). B: Glutathione levels in cells of the control solution (without additives in the test sample). <Results> The glutathione production promotion rate is shown in Table 12 below. Mangiferin confirmed a significant glutathione production promotion effect.

[0278] [Table 12] (Experiment 10: Experiment on the Promotion of ATP Production) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume FBS.

[0279] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS.

[0280] -Pre-culture of normal human hepatocytes- Normal human hepatocytes (obtained from DS Pharmace Biomedical) were cultured in DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were cultured to a density of 2.0 × 10⁶ cells / mL. 5 The cell / mL concentration was diluted with DMEM containing 10% FBS by volume, and 100 μL was seeded into each well of a 96-well plate and cultured overnight at 37°C and 5% CO2.

[0281] -Determination of the test sample solution- The culture medium was removed from each well of previously cultured normal human hepatocytes. 100 μL of the test sample solution was added to achieve the final concentration shown in Table 13 below, and the cells were cultured at 37°C and 5% CO2 for 2 hours. The ATP production promotion effect was assessed using a firefly luciferase assay to determine the intracellular ATP level. Specifically, after culture, the ATP was measured using the ATP assay reagent (“Cellular” ATP assay reagent). TM 100 μL of the solution (Ver.2, manufactured by Toyo B-Net Co., Ltd.) was added to each well, and the chemiluminescence amount was measured after the reaction.

[0282] -Determination of the control solution- In the determination of the test sample solution, 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 10% FBS by volume. Otherwise, the control solution was determined using the same method as the test sample solution.

[0283] -Calculation of the ATP production promotion rate- Based on the chemiluminescence amount obtained by measuring the test sample solution, the positive control sample solution, and the control solution, the ATP production promotion rate is calculated using the following formula (10).

[0284] ATP production promotion rate (%) = A / B × 100 Equation (10) In the above formula (10), “A” and “B” are respectively as follows: A: Chemiluminescence levels in cells of the test sample solution (when the test sample is added). B: Chemiluminescence levels in cells of the control solution (without additives in the test sample). <Results> The ATP production promotion rate is shown in Table 13 below. Mangiferin confirmed a significant ATP production promotion effect.

[0285] [Table 13] (Experiment 11: Hepatocyte proliferation promotion experiment) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 1 volume % FBS.

[0286] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 1 volume % FBS.

[0287] -Pre-culture of normal human hepatocytes- Normal human hepatocytes (obtained from DS Pharmace Biomedical) were cultured in DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were cultured to a density of 1.25 × 10⁶ cells / mL. 4 The cell / mL concentration was diluted with DMEM containing 10% FBS by volume, and 100 μL was seeded into each well of a 96-well plate and cultured overnight at 37°C and 5% CO2.

[0288] -Determination of the test sample solution- Culture medium was removed from each well of previously cultured normal human hepatocytes. 200 μL of the test sample solution was added to each well as shown in Table 14 below, and the cells were cultured at 37°C and 5% CO2 for 3 days. The proliferation-promoting effect on normal human hepatocytes was determined using the MTT assay. After culture, the culture medium was removed, and 100 μL of MTT (prepared by Dojin Chemical Research Institute) dissolved in PBS (-) at a final concentration of 0.4 mg / mL was added to each well. After culturing at 37°C and 5% CO2 for 2 hours, the blue formazan generated intracellularly was extracted using 100 μL of 2-propanol. After extraction, the absorbance at 570 nm was measured. Simultaneously, the absorbance at 650 nm was measured as turbidity. The amount of blue formazan generated was obtained based on the difference between the two (absorbance at 570 nm - absorbance at 650 nm).

[0289] -Determination of the control solution- In the determination of the test sample solution, 200 μL of the test sample solution was replaced with 200 μL of DMEM containing 10% FBS by volume. Otherwise, the control solution was determined using the same method as the test sample solution.

[0290] -Calculation of the rate of hepatocyte proliferation promotion in normal individuals- Based on the amount of blue scab produced by measuring the test sample solution and the control solution, the astrocyte proliferation promotion rate is calculated using the following formula (11).

[0291] Astrocyte proliferation promotion rate (%) = A / B × 100 Equation (11) In the above formula (11), “A” and “B” are as follows: A: The amount of blue formazan produced in cells of the test sample solution (when the test sample was added). B: Blue formazan production in cells of the control solution (without additives to the test sample). <Results> The rate of hepatocyte proliferation promotion in normal human subjects is shown in Table 14 below. As shown in Table 14 below, mangiferin confirmed a significant hepatocyte proliferation promotion effect in normal human subjects.

[0292] [Table 14] (Experiment 12: Experiment on the promoting effect of type I collagen production in osteoblasts) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in FBS-free High-DMEM (high glucose (manufactured by Fujifilm and Kojun Pharmaceutical Co., Ltd.) with 20 mmol / L HEPES, manufactured by SIGMA; the same substance was used for High-DMEM in the following test examples).

[0293] In addition, the mangiferin used as the test sample was a solution in which ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) was dissolved in FBS-free High-DMEM.

[0294] -Preculture of human osteoblastic cells (SaM-1)- Human osteoblastic cells (SaM-1) were cultured in High-DMEM containing 10% FBS and then recovered using trypsin. The recovered cells were then divided into groups of 6 × 10⁶ cells. 4 At a cell / mL concentration, after dilution with High-DMEM containing 10% FBS, 200 μL was seeded into each well of a 96-well plate and cultured at 37°C and 5% CO2 for 3 days.

[0295] -Determination of the test sample solution- After pre-culture, the cells were washed with 100 μL / well of PBS (-), and the medium was replaced with 100 μL / well of FBS-free High-DMEM. After 24 hours of incubation at 37°C and 5% CO2, 100 μL of the test sample was added to each well to achieve the final concentration shown in Table 15 below, and the cells were incubated at 37°C and 5% CO2 for 3 days. After incubation, the amount of type I collagen in the medium of each well was determined by a sandwich ELISA method using a polyclonal antibody to collagen type I (Acris). In addition, the cell viability of each well was determined by the WST8 assay using the Cell Counting Kit-8 (Dongjin Chemical Research Institute).

[0296] -Determination of the control solution- In the determination of the test sample solution, 100 μL of the test sample solution was replaced with 100 μL of FBS-free High-DMEM. Otherwise, the control solution was determined using the same method as the test sample solution.

[0297] Calculation of the type I collagen production promotion rate- Based on the amount of type I collagen obtained by measuring the test sample solution and the control solution, the type I collagen production promotion rate is calculated using the following formula (12).

[0298] Type I collagen production promotion rate (%) = A / B × 100 Equation (12) In the above formula (12), “A” and “B” are as follows: A: Type I collagen content in the test sample solution (when the test sample is added). B: Type I collagen content in the control solution (when the tested sample was not added). <Results> The rate of promotion of type I collagen production is shown in Table 15 below. As shown in Table 15 below, mangiferin confirmed a significant promotion effect on type I collagen production.

[0299] [Table 15] (Experimental Example 13: DPPIV Activity Inhibition Test) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was a solution in which M3547 (batch number: SLBQ6689V, manufactured by SIGMA) was dissolved in 25 mmol / L Tris-HCl buffer (pH 8.0).

[0300] In addition, the mangiferin used as the test sample was a solution in which ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) was dissolved in 25 mmol / L Tris-HCl buffer (pH 8.0).

[0301] -Determination of the test sample solution- For a 96-well plate, 25 μL of the test sample solution and 25 μL of 0.4 μg / mL DPPIV (rhCD26) solution (manufactured by R&D Systems) were added and mixed, and pre-incubated at 37°C for 5 minutes. The test sample solution was added to the final concentration shown in Table 16 below. Then, 50 μL of 0.5 mmol / L Gly-Pro-p-NA·Tos[GPNT] solution (manufactured by Peptide Research Institute Co., Ltd.) prepared with 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the reaction was carried out at 37°C for 90 minutes. After the reaction, the absorbance was measured at a wavelength of 415 nm.

[0302] -Determination of the blank in the test sample solution- For 96-well plates, without adding 0.4 μg / mL DPPIV (rhCD26) solution, 25 μL of the test sample solution and 25 μL of 25 mmol / L Tris-HCl buffer (pH 8.0) were added and mixed, and pre-incubated at 37°C for 5 minutes. The test sample solution was added to the final concentration shown in Table 16 below. Then, 50 μL of 0.5 mmol / L Gly-Pro-p-NA·Tos[GPNT] solution prepared with 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the reaction was carried out at 37°C for 90 minutes. After the reaction, the absorbance was measured at a wavelength of 415 nm.

[0303] -Determination of the control solution- For the 96-well plate, without the test sample solution, 25 μL of 25 mmol / L Tris-HCl buffer (pH 8.0) and 25 μL of 0.4 μg / mL DPPIV (rhCD26) solution were added and pre-incubated at 37°C for 5 minutes. Then, 50 μL of 0.5 mmol / L Gly-Pro-p-NA·Tos[GPNT] solution prepared with 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the reaction was carried out at 37°C for 90 minutes. After the reaction, the absorbance was measured at a wavelength of 415 nm.

[0304] -Determination of blank control solution- For 96-well plates, without the test sample solution and 0.4 μg / mL DPPIV (rhCD26) solution, 50 μL of 25 mmol / L Tris-HCl buffer (pH 8.0) was pre-incubated at 37°C for 5 min. Then, 50 μL of 0.5 mmol / L Gly-Pro-p-NA·Tos[GPNT] solution prepared with 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the reaction was carried out at 37°C for 90 min. After the reaction, the absorbance was measured at a wavelength of 415 nm.

[0305] -Calculation of DPPIV activity inhibition rate- Based on the absorbance obtained by measuring the test sample solution, the control solution, and the control blank, the DPPIV activity inhibition rate is calculated using the following formula (13).

[0306] DPPIV activity inhibition rate (%) = {1 - (AB) / (CD)} × 100 Equation (13) In the above formula (13), “A”, “B”, “C”, and “D” are as follows: A: Absorbance of the test sample solution (test sample added, enzyme added) at a wavelength of 415 nm. B: Absorbance of the blank test sample solution (with or without added enzyme) at a wavelength of 415 nm. C: Absorbance of the control solution (test sample with no additives or with added enzymes) at a wavelength of 415 nm. D: Absorbance of the control solution blank (test sample without additives, enzyme without additives) at a wavelength of 415 nm. <Results> The DPPIV activity inhibition rates are shown in Table 16 below. As shown in Table 16 below, both mangiferin and mangiferin were found to have weak DPPIV activity inhibition effects.

[0307] [Table 16] (Experiment 14: Assay on the effect of promoting myoblast proliferation) <Experimental Methods> -Preparation of the test sample solution- The mangiferin used as the test sample was prepared by dissolving M3547 (batch number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 5% FBS by volume.

[0308] In addition, the mangiferin used as the test sample was prepared by dissolving ALB-RS-1643 (batch number: ALB-202105, manufactured by SIGMA) in DMEM containing 5% FBS by volume.

[0309] -Preculture of mouse skeletal muscle-derived myoblasts- Mouse skeletal muscle-derived myoblasts (C2C12) (obtained from DS Pharmace Biomedical) were cultured in DMEM containing 10% FBS and then recovered using a cell scraper. The recovered cells were cultured to a density of 2.0 × 10⁶ cells / mL. 4 The cell / mL concentration was diluted with DMEM containing 5% FBS by volume, and 100 μL was seeded into each well of a collagen-coated 96-well plate (made by IWAKI) and cultured at 37°C and 5% CO2 for 6 hours.

[0310] -Determination of the test sample solution- 100 μL of the test sample solution was added to each well of pre-cultured mouse skeletal muscle-derived myoblasts (C2C12) to achieve the final concentration shown in Table 17 below, and cultured at 37°C and 5% CO2 for 2 days. The myoblast proliferation-promoting effect was determined using the MTT assay. After culture, the culture medium was removed, and 100 μL of MTT (prepared by Dojin Chemical Research Institute) solution (final concentration 0.4 mg / mL, dissolved in PBS-) was added to each well. After culturing at 37°C and 5% CO2 for 2 hours, the blue formazan generated intracellularly was extracted using 100 μL of 2-propanol. The absorbance at 570 nm was measured after extraction. Simultaneously, the absorbance at 650 nm was measured as turbidity, and the amount of blue formazan generated was obtained based on the difference between the two (absorbance at 570 nm - absorbance at 650 nm).

[0311] -Determination of the control solution- In the determination of the test sample solution, 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 5 volume% FBS. Otherwise, the control solution was determined using the same method as the test sample solution.

[0312] -Calculation of the rate of increase in myoblast proliferation- Based on the amount of blue cyanide produced by measuring the test sample solution and the control solution, the myoblast proliferation promotion rate is calculated using the following formula (14).

[0313] Astrocyte proliferation promotion rate (%) = A / B × 100 (Equation 14) In the above formula (14), “A” and “B” are as follows: A: The amount of blue formazan produced in cells of the test sample solution (when the test sample was added). B: Blue formazan production in cells of the control solution (without additives to the test sample). <Results> The rate of myoblast proliferation promotion is shown in Table 17 below. As shown in Table 17 below, mangiferin and mangiferin at low concentrations confirmed a significant myoblast proliferation-promoting effect.

[0314] [Table 17] As an example of the present invention, the following can be cited.

[0315] [1] An anti-obesity agent, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0316] [Chemistry 19] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0317] [Chemistry 20] In the above general formula (2), * represents a bonding bond.

[0318] [2] The anti-obesity agent according to [1] above has one or more effects selected from the group consisting of α-glucosidase activity inhibition and lipase activity inhibition.

[0319] [3] An anti-inflammatory agent, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0320] [Chemistry 21] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0321] [Chemistry 22] In the above general formula (2), * represents a bonding bond.

[0322] [4] The anti-inflammatory agent according to [3] above has one or more effects selected from the group consisting of inhibition of free aminohexosidase and inhibition of prostaglandin E2 production.

[0323] [5] A brain function improver, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0324] [Chemistry 23] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0325] [Chemistry 24] In the above general formula (2), * represents a bonding bond.

[0326] [6] The brain function improver described in [5] above has one or more of the following effects: promoting cell proliferation of astrocytes, promoting the expression of aquaporin 4 mRNA in astrocytes, inhibiting the production of tumor necrosis factor (TNF-α) in microglia, inhibiting the expression of inflammatory inducing factor-related genes in microglia, and increasing the expression of inflammatory suppressor-related genes in microglia.

[0327] [7] A liver function improver, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0328] [Chemistry 25] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0329] [Chemistry 26] In the above general formula (2), * represents a bonding bond.

[0330] [8] The liver function improver described in [7] above has one or more effects selected from the group consisting of promoting glutathione production in hepatocytes, promoting ATP production in hepatocytes, and promoting hepatocyte proliferation.

[0331] [9] A bone strengthening agent, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0332] [Chemistry 27] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0333] [Chemistry 28] In the above general formula (2), * represents a bonding bond.

[0334]

[10] The bone strengthening agent described in [9] above has a type I collagen production promoting effect.

[0335]

[11] A blood glucose level improver, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0336] [Chemistry 29] In the above general formula (1), R1 It represents H or the group represented by the following general formula (2).

[0337] [Chemistry 30] In the above general formula (2), * represents a bonding bond.

[0338]

[12] The blood glucose improver described in

[11] above has an inhibitory effect on dipeptidyl peptidase IV activity.

[0339]

[13] A muscle enhancer, characterized in that it contains a compound represented by the following general formula (1) as an active ingredient.

[0340] [Chemistry 31] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0341] [Chemistry 32] In the above general formula (2), * represents a bonding bond.

[0342]

[14] The muscle enhancer described in

[13] above has a myoblast proliferation promoting effect.

[0343]

[15] An oral composition, characterized in that it contains at least one of the following: an anti-obesity agent selected from any one of [1] to [2], an anti-inflammatory agent selected from any one of [3] to [4], a brain function improver selected from any one of [5] to [6], a liver function improver selected from any one of [7] to [8], a bone enhancer selected from any one of [9] to

[10] , a blood glucose improver selected from any one of

[11] to

[12] , and a muscle enhancer selected from any one of

[13] to

[14] .

[0344]

[16] A cosmetic composition, characterized in that it contains at least one of the following: an anti-obesity agent selected from any one of [1] to [2], an anti-inflammatory agent selected from any one of [3] to [4], a brain function improver selected from any one of [5] to [6], a liver function improver selected from any one of [7] to [8], a bone enhancer selected from any one of [9] to

[10] , a blood glucose improver selected from any one of

[11] to

[12] , and a muscle enhancer selected from any one of

[13] to

[14] .

[0345]

[17] The compounds represented by the following general formula (1) for use in anti-obesity, anti-inflammatory, brain function enhancement, liver function enhancement, bone strengthening, blood glucose improvement, or muscle strengthening.

[0346] [Chemistry 33] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0347] [Chemistry 34] In the above general formula (2), * represents a bonding bond.

[0348]

[18] According to the compound described in

[17] above, the use in the anti-obesity process is the use of one or more compounds selected from the group consisting of inhibition of α-glucosidase activity and inhibition of lipase activity.

[0349]

[19] According to the compound described in

[17] above, the use in the anti-inflammatory activity is selected from one or more of the group consisting of free inhibition of aminohexosidase and inhibition of prostaglandin E2 production.

[0350]

[20] According to the compound described in

[17] above, the use of the above-mentioned brain function enhancement is selected from one or more of the following groups: promoting cell proliferation of astrocytes, promoting the expression of aquaporin 4 mRNA in astrocytes, inhibiting the production of tumor necrosis factor (TNF-α) in microglia, inhibiting the expression of inflammatory inducing factor-related genes in microglia, and increasing the expression of inflammatory suppressor-related genes in microglia.

[0351]

[21] According to the compound described in

[17] above, the use of the above-mentioned liver function enhancement is selected from one or more of the group consisting of promoting the production of glutathione in hepatocytes, promoting the production of ATP in hepatocytes, and promoting the proliferation of hepatocytes.

[0352]

[22] According to the compound described in

[17] above, the use in the above-mentioned bone strengthening is the use in promoting the production of type I collagen.

[0353]

[23] According to the compound described in

[17] above, the use in improving blood glucose levels is the use in inhibiting the activity of dipeptidyl peptidase IV.

[0354]

[24] According to the compound described in

[17] above, the use in muscle strengthening is the use in promoting myoblast proliferation.

[0355]

[25] The use of the compound according to any one of

[17] to

[24] above, which is used for oral administration.

[0356]

[26] The use of the compound according to any one of

[17] to

[24] above, which is used in cosmetics.

[0357]

[27] The use of compounds represented by the following general formula (1) in the manufacture of pharmaceuticals for anti-obesity, anti-inflammatory, brain function improvement, liver function improvement, bone strengthening, blood glucose improvement, or muscle strengthening.

[0358] [Chemistry 35] In the above general formula (1), R 1 It represents H or the group represented by the following general formula (2).

[0359] [Chemistry 36] In the above general formula (2), * represents a bonding bond.

[0360]

[28] Based on the use of the compound described in

[27] above, the above-mentioned anti-obesity pharmaceutical product has one or more effects selected from the group consisting of α-glucosidase activity inhibition and lipase activity inhibition.

[0361]

[29] Based on the use of the compound described in

[17] above, the above-mentioned anti-inflammatory medicine has one or more effects selected from the group consisting of free inhibition of aminohexosidase and inhibition of prostaglandin E2 production.

[0362]

[30] According to the use of the compound described in

[17] above, the above-mentioned pharmaceutical product for improving brain function has one or more effects selected from the group consisting of promoting the expression of aquaporin 4 mRNA in astrocytes, inhibiting the production of tumor necrosis factor (TNF-α) in microglia, inhibiting the expression of inflammatory inducing factor-related genes in microglia, and increasing the expression of inflammatory suppressor-related genes in microglia.

[0363]

[31] Based on the use of the compound described in

[17] above, the above-mentioned pharmaceutical product for improving liver function has one or more effects selected from the group consisting of promoting glutathione production in hepatocytes, promoting ATP production in hepatocytes, and promoting hepatocyte proliferation.

[0364]

[32] Based on the use of the compound described in

[17] above, the above-mentioned pharmaceutical product for bone strengthening has a type I collagen production promoting effect.

[0365]

[33] Based on the use of the compound described in

[17] above, the above-mentioned pharmaceutical product for improving blood glucose levels has an inhibitory effect on dipeptidyl peptidase IV activity.

[0366]

[34] Based on the use of the compound described in

[17] above, the above-mentioned pharmaceutical product for muscle strengthening has a myoblast proliferation promoting effect.

[0367]

[35] The use of the compound according to any one of

[27] to

[34] above, which is used for oral administration.

[0368]

[36] The use of the compound according to any one of

[27] to

[34] above, which is used in cosmetics.

[0369] This international application claims priority based on Japanese Patent Application No. 2023-221743, filed on December 27, 2023, and incorporates the entire contents of Japanese Patent Application No. 2023-221743.

Claims

1. An anti-obesity agent, characterized in that, The active ingredient contains a compound represented by the following general formula (1). [Chemistry 1] In the general formula (1), R 1 Represents H or the group shown in the following general formula (2), [Chemistry 2] In the general formula (2), * represents a bonding bond.

2. The anti-obesity agent according to claim 1, having one or more effects selected from the group consisting of α-glucosidase activity inhibition and lipase activity inhibition.

3. An anti-inflammatory agent, characterized in that, The active ingredient contains a compound represented by the following general formula (1). [Chemistry 3] In the general formula (1), R 1 Represents H or the group shown in the following general formula (2), [Chemistry 4] In the general formula (2), * represents a bonding bond.

4. The anti-inflammatory agent according to claim 3, having one or more effects selected from the group consisting of inhibition of aminohexosidase free activity and inhibition of prostaglandin E2 production.

5. A brain function improver, characterized in that, The active ingredient contains a compound represented by the following general formula (1). [Chemistry 5] In the general formula (1), R 1 Represents H or the group shown in the following general formula (2), [Chemistry 6] In the general formula (2), * represents a bonding bond.

6. The brain function improver according to claim 5, having one or more of the following effects selected from the group consisting of promoting cell proliferation of astrocytes, promoting aquaporin 4 mRNA expression in astrocytes, inhibiting the production of tumor necrosis factor (TNF-α) in microglia, inhibiting the expression of inflammatory inducing factor-related genes in microglia, and increasing the expression of inflammatory suppressor-related genes in microglia.

7. A liver function improver, characterized in that, The active ingredient contains a compound represented by the following general formula (1). [Chemistry 7] In the general formula (1), R 1 Represents H or the group shown in the following general formula (2), [Chemistry 8] In the general formula (2), * represents a bonding bond.

8. The liver function improver according to claim 7, having one or more effects selected from the group consisting of promoting glutathione production in hepatocytes, promoting ATP production in hepatocytes, and promoting hepatocyte proliferation.

9. A bone strengthening agent, characterized in that, The active ingredient contains a compound represented by the following general formula (1). [Chemistry 9] In the general formula (1), R 1 Represents H or the group shown in the following general formula (2), [Chemistry 10] In the general formula (2), * represents a bonding bond.

10. The bone strengthening agent according to claim 9, which has a type I collagen production promoting effect.

11. A blood glucose level improver, characterized in that, The active ingredient contains a compound represented by the following general formula (1). [Chemistry 11] In the general formula (1), R 1 Represents H or the group shown in the following general formula (2), [Chemistry 12] In the general formula (2), * represents a bonding bond.

12. The blood glucose improver according to claim 11, which has an inhibitory effect on dipeptidyl peptidase IV activity.

13. A muscle enhancer, characterized in that, The active ingredient contains a compound represented by the following general formula (1). [Chemistry 13] In the general formula (1), R 1 Represents H or the group shown in the following general formula (2), [Chemistry 14] In the general formula (2), * represents a bonding bond.

14. The muscle enhancer according to claim 13, which has a myoblast proliferation promoting effect.

15. An oral composition, characterized in that, It contains at least one selected from the group consisting of the anti-obesity agent of claim 1, the anti-inflammatory agent of claim 3, the brain function improver of claim 5, the liver function improver of claim 7, the bone enhancer of claim 9, the blood glucose improver of claim 11, and the muscle enhancer of claim 13.

16. A cosmetic composition, characterized in that, It contains at least one selected from the group consisting of the anti-obesity agent of claim 1, the anti-inflammatory agent of claim 3, the brain function improver of claim 5, the liver function improver of claim 7, the bone enhancer of claim 9, the blood glucose improver of claim 11, and the muscle enhancer of claim 13.

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