Anti-obesity agent, Anti-inflammatory agent, brain function improving agent, liver function improving agent, bone strengthening agent, blood sugar level improving agent, muscle enhancing agent, oral composition, and cosmetic composition

Abstract

Provided are: an anti-obesity agent, an anti-inflammatory agent, a brain function improving agent, a liver function improving agent, a bone strengthening agent, a blood sugar level improving agent, and a muscle enhancing agent each containing a compound represented by general formula (1) as an active ingredient; and an oral composition and a cosmetic composition each containing at least any one of the above-mentioned agents. (In general formula (1), R1 represents H or a group represented by general formula (2). In general formula (2), * represents a bond.)

Description

Anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengthening agents, blood sugar level improving agents, muscle strengthening agents, oral compositions, and cosmetic compositions

[0001] The present invention relates to an anti-obesity agent, an anti-inflammatory agent, a brain function improver, a liver function improver, a bone strengthener, a blood sugar level improver, a muscle strengthener, an oral composition, and a cosmetic composition.

[0002] In recent years, lifestyle habits such as overeating and lack of exercise have led to an increase in body fat and an increase in obesity. This increase in obesity is not only seen in humans, but also in pets and livestock. Obesity can lead to adult diseases such as hyperlipidemia and arteriosclerosis, so it is not only a problem in terms of beauty but also a major health issue.

[0003] Methods for preventing and treating obesity include, for example, restricting dietary intake and burning fat through various aerobic exercises. These methods are not effective because they are difficult to achieve results in a short period of time and may cause physical and mental pain. For this reason, methods for preventing and treating obesity using anti-obesity agents (e.g., pharmaceuticals, foods and beverages, feeds, cosmetic compositions, etc.) are commonly used.

[0004] As an active ingredient of an anti-obesity agent, a substance that inhibits the activity of enzymes involved in carbohydrate or fat metabolism, such as lipase, α-glucosidase, etc. Known examples of substances that have such inhibitory effects include catechin and plant extracts (see, for example, Patent Documents 1 and 2).

[0005] Inflammatory diseases, such as contact dermatitis (rash), psoriasis, pemphigus vulgaris, atopic dermatitis, and other skin inflammatory diseases accompanied by rough skin, as well as rheumatoid arthritis, osteoarthritis, and asthma, have a wide variety of causes and onset mechanisms. The causes include those due to the release of histamine, prostaglandin E2 (PGE ２ It is known that the cause is increased production of cyclooxygenase-2 (COX-2) (increased activity of cyclooxygenase-2).

[0006] Histamine release is a phenomenon in which histamine in mast cells is released outside the cells, and the released histamine causes an inflammatory reaction. Therefore, attempts have been made to prevent or treat allergic diseases and inflammatory diseases using substances that inhibit or suppress histamine release. However, it is difficult to directly evaluate histamine release, and histamine release can be evaluated using the release of hexosaminidase, which has been confirmed to be released simultaneously with histamine release, as an indicator. Therefore, by inhibiting the release of hexosaminidase, histamine release can also be inhibited, which is thought to be effective in preventing, treating, or improving inflammatory diseases, etc.

[0007] Histamine also mediates intercellular communication as a local neurotransmitter, promoting gastric acid secretion in the digestive tract and functioning as a neurotransmitter in the central nervous system, contributing to maintaining a waking state. Excessive histamine release can cause ulcers due to gastric hyperacidity in the digestive tract and contributes to sleep disorders in the central nervous system. As mentioned above, inhibiting the release of hexosaminidase can simultaneously inhibit the release of histamine, which is believed to prevent, treat, or improve gastric ulcers, sleep disorders, and other conditions caused by gastric hyperacidity. For example, extracts from wisteria tea (see, for example, Patent Document 3) are known to have the effect of inhibiting hexosaminidase release.

[0008] In recent years, as society has become increasingly aging, the desire to stay healthy both physically and mentally has become stronger. As people age, their memory and learning abilities gradually decline. Furthermore, in diseases such as Alzheimer's disease and Parkinson's disease, cognitive impairment due to neurodegeneration has become a major problem. Meanwhile, the number of patients with brain function problems, including mood disorders such as depression caused by various stressors such as work environment, family circumstances, and interpersonal relationships, is increasing year by year, even among those who are not elderly.

[0009] Methods for improving brain function that have been studied include improving the supply of nutrients and oxygen to nerve cells in the brain (for example, increasing intracerebral glucose, improving blood flow, etc.); improving neurotransmission that takes place in the synaptic cleft (supplying neurotransmitter precursors, increasing neurotransmitter release, activating receptors, inhibiting the conversion of released neurotransmitters, etc.); and so on.

[0010] In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein waste products such as amyloid beta and alpha-synuclein accumulate in the brain without being removed, and this accumulation of waste products is thought to be one of the causes of the aforementioned neurodegenerative diseases. While the lymphatic system contributes to the removal of protein waste products in other parts of the body, the brain does not have a lymphatic system, and therefore it was thought that protein waste products were broken down and removed in the brain. However, in recent years, it has been discovered that cerebrospinal fluid (CSF) flowing through perivascular spaces and astrocytes contributes to the removal of protein waste products in the brain, and that aquaporin 4 (AQP4), a water channel highly expressed in astrocytes, significantly contributes to the flow of CSF (see Non-Patent Document 1). Furthermore, it has been reported that the flow of CSF increases during sleep and anesthesia, and the rate of amyloid beta removal also increases (see Non-Patent Document 2). This series of brain pathways has been named the "glymphatic system" and has attracted attention. Therefore, if the flow rate of this glymphatic system can be increased, waste proteins such as amyloid beta and alpha-synuclein can be efficiently removed from the brain, which is expected to lead to the prevention, treatment, or improvement of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.

[0011] Furthermore, it is becoming clear that activation of astrocytes, microglia, and the like is associated with various brain dysfunctions. For example, in the aging brain, microglia become activated, leading to increased production of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, etc.) and nitric oxide (NO), a neuropathic factor, and other neuropathic factors, resulting in neuropathies (see, for example, Patent Document 4). It has been found that the progression or chronicity of neuropathies is associated with cognitive dysfunction, depression, and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (see Non-Patent Document 3). Therefore, if neuropathies can be suppressed, it is possible to improve cognitive function (memory ability, learning ability, etc.) that has declined due to neuropathies caused by aging, etc., and it is also believed that this could lead to the prevention, treatment, or amelioration of cognitive dysfunction, mood disorders, and even neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (see Non-Patent Document 4). On the other hand, it is also known that interleukin-10 (IL-10) acts as a neuroprotective factor that suppresses neurological disorders in the brain (see Non-Patent Documents 5 and 6).

[0012] The liver is an extremely important organ for humans, performing many vital functions, such as metabolizing and storing various nutrients absorbed by the intestine, as well as producing and secreting bile, detoxifying and excreting. However, the liver is susceptible to acute or chronic damage caused by various factors, such as irregular lifestyles, stress, viruses, drugs, alcohol, malnutrition, and hepatic circulatory system disorders, which can lead to diseases (liver dysfunction) such as acute hepatitis, chronic hepatitis, fatty liver, jaundice, and cirrhosis.

[0013] Glutathione is a tripeptide composed of three amino acids, glutamic acid, cysteine, and glycine, and is a compound containing the major intracellular cysteine ​​residue. In the liver, glutathione not only protects hepatocytes from various oxidative stresses but also directly contributes to the expression of liver functions such as drug metabolism by forming conjugates with harmful substances such as drugs and reactive compounds and excreting them extracellularly. However, the exertion of glutathione's effects also results in the consumption of glutathione. In fact, it is known that when liver damage is induced in rats with galactosamine or other substances, the amount of glutathione in hepatocytes decreases. Therefore, promoting glutathione production in the liver is thought to suppress liver damage and ultimately lead to improved liver function. Amber hot water extract (see, for example, Patent Document 5) is known to have the effect of promoting glutathione production.

[0014] Furthermore, in order to promote cell proliferation, it is important to supply cells with the energy necessary for cell division. ATP is an example of an energy substance in living organisms, and increasing the amount of ATP production is thought to promote intracellular energy metabolism and lead to cell proliferation. However, it has been reported that the amount of ATP, an energy substance, is reduced in cells with reduced function or aging cells compared to normal cells (see, for example, Patent Document 6). Therefore, if ATP production in cells can be promoted, it is thought that the cells can be activated, cell division can be promoted, and the proliferation ability of the cells can be restored.

[0015] Bone is a tissue whose main components are hydroxyapatite, a type of calcium phosphate, and type I collagen. It not only supports our bodies but also plays an important role in maintaining blood calcium levels and producing blood. Bone is formed by osteoblasts, which differentiate from mesenchymal stem cells, calcifying bone matrix proteins and matrix vesicles, and is then resorbed (destroyed) by osteoclasts. Thus, bone formation and resorption (destruction) are constantly repeated (bone remodeling), and normal bone density is maintained by balancing this bone metabolism (see Non-Patent Document 7).

[0016] In recent years, the aging of society and changes in dietary habits have disrupted the balance of bone remodeling, leading to an increase in the number of patients with bone diseases. Osteoporosis, a representative example of bone-related disease, is a disease caused mainly by a decrease in bone density due to increased bone resorption. In addition to osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontal disease are also bone-related diseases closely associated with abnormal bone remodeling.

[0017] Therefore, it is believed that promoting bone formation and correcting abnormalities in bone remodeling can prevent, treat, and improve bone-related diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontal disease. Royal jelly, glucosamine, and chondroitin sulfate (see Patent Document 7) are known as components that promote bone formation.

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

[0019] Substrates of DPPIV include hormones called incretins. Incretins are a collective term for hormones secreted from the intestinal tract in response to nutrient stimulation and promote insulin secretion from pancreatic β cells in a blood glucose-dependent manner. Known examples include GLP-1 and GIP. These incretins not only promote blood glucose-dependent insulin secretion, but also suppress glucagon secretion from pancreatic α cells, lower blood pressure, inhibit gastric emptying, and even suppress food intake by acting on the hypothalamus (see Non-Patent Document 8). However, because incretins are degraded by DPPIV, the half-life of GLP-1 in vivo is known to be approximately 1.5 minutes. Therefore, if the enzymatic activity of DPPIV can be inhibited, the half-life of incretins in vivo can be extended, which is expected to be useful in treating type 2 diabetes, obesity, hypertension, insulin resistance, and the like through the aforementioned incretin action.

[0020] Furthermore, DPPIV is identical to CD26, a T cell activation marker, and is known to use many immunoregulatory peptides as substrates and regulate their activity. Therefore, it is believed that regulating DPPIV activity can control immune responses, such as autoimmune diseases such as rheumatoid arthritis and transplant rejection. Furthermore, DPPIV is known to be involved in the metabolism of several neuropeptides and growth hormones; cancer invasion, metastasis, angiogenesis, etc.; and HIV infection of lymphocytes. Therefore, it is believed that inhibiting DPPIV activity can treat diseases such as pain, neurodegenerative diseases, and neuropsychiatric disorders (e.g., sciatica, Alzheimer's disease, depression, etc.); growth hormone deficiency and diseases for which growth hormone is used in the treatment; cancer (e.g., T-cell lymphoma, acute lymphoblastic leukemia, thyroid cancer, basal cell carcinoma, breast cancer, etc.); and HIV infection (AIDS).

[0021] When we exercise, it is our muscles that are responsible for the movement, and strengthening muscle function is necessary to improve athletic ability. This is not limited to athletes; for the general public, muscles are extremely important for everyday light exercise, maintaining posture, and other healthy daily activities. Furthermore, muscles not only function to move the body, but also have various functions such as using glucose to control blood sugar levels, regulating body temperature through heat production, and regulating fat mass through the use of lipids, and are therefore thought to be important for maintaining health.

[0022] Muscles are formed by the fusion of mononuclear myoblasts to form elongated, multinucleated myotubes. The myotubes then aggregate and align to form muscle fibers, generating the muscle's great strength. Thus, myogenesis is a complex process consisting of myoblast proliferation and differentiation, muscle cell recognition, adhesion, and fusion. Medium-chain fatty acids such as decenoic acid, decenedioic acid, and sebacic acid (see, for example, Patent Document 8) are known to promote myoblast proliferation.

[0023] JP 2016-027812 A JP 2012-051916 A JP 2003-012532 A JP 2022-183626 A JP 2010-235551 A JP 2003-321373 A JP 2019-062931 A JP 2020-089278 A

[0024] Jeffrey J Iliff et al. , Sci Transl Med. , 2012, Vol. 4, issue 147, pp. 147ra111Lulu Xie et al. , Science, 2013, Vol. 342, issue 6156, pp. 373-377 Akio Susumura, Clinical Neurology, 2014, Volume 54, No. 12, pp. 1119-1121 Akira Moji, Journal of Psychiatry and Neurology, 2012, Volume 114, Issue 2, pp. 124-133 Diana M. Norden et al. , Glia, 2014, Vol. 62, issue 6, pp. 881-895Anton Reiner et al. , Int. J. Mol. Sci. , 2015, Vol. 16, issue 1, pp. 758-787 Shu Takeda, Journal of the Japanese Kidney Society, 2014, Volume 56, Issue 8, p. 1188-1195. Nobuyuki Yasuda et al., Japanese Pharmacological Journal, 2005, Volume 125, Issue 6, p. 379-384

[0025] The present invention aims to provide an anti-obesity agent having an excellent anti-obesity effect and being highly safe, an anti-inflammatory agent having an excellent anti-inflammatory effect and being highly safe, a brain function improving agent having an excellent brain function improving effect and being highly safe, a liver function improving agent having an excellent liver function improving effect and being highly safe, a bone strengthening agent having an excellent bone strengthening effect and being highly safe, a blood sugar level improving agent having an excellent blood sugar level improving effect and being highly safe, a muscle strengthening agent having an excellent muscle strengthening effect and being highly safe, and oral compositions and cosmetic compositions containing these.

[0026] The means for solving the above problems are as follows: <1> An anti-obesity agent characterized by containing a compound represented by the following general formula (1) as an active ingredient. However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the formula (2), * represents a bond. <2> An anti-inflammatory agent characterized by containing a compound represented by the following formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the formula (2), * represents a bond. <3> A brain function enhancer comprising a compound represented by the following formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the formula (2), * represents a bond. <4> A liver function improver characterized by containing a compound represented by the following formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the above general formula (2), * represents a bond. <5> A bone strengthening agent characterized by containing a compound represented by the following general formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the formula (2), * represents a bond. <6> A blood sugar level-improving agent characterized by containing a compound represented by the following formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond. <7> A muscle strengthening agent characterized by containing a compound represented by the following general formula (1) as an active ingredient. However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond. <8> An oral composition comprising 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 strengthening agent described in <5>, the blood glucose level improving agent described in <6>, and the muscle strengthening agent described in <7>. <9> A cosmetic composition comprising 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 strengthening agent described in <5>, the blood glucose level improving agent described in <6>, and the muscle strengthening agent described in <7>.

[0027] According to the present invention, it is possible to provide an anti-obesity agent having an excellent anti-obesity effect and being highly safe, an anti-inflammatory agent having an excellent anti-inflammatory effect and being highly safe, a brain function improving agent having an excellent brain function improving effect and being highly safe, a liver function improving agent having an excellent liver function improving effect and being highly safe, a bone strengthening agent having an excellent bone strengthening effect and being highly safe, a blood sugar level improving agent having an excellent blood sugar level improving effect and being highly safe, a muscle strengthening agent having an excellent muscle strengthening effect and being highly safe, and oral compositions and cosmetic compositions containing these.

[0028] (Anti-obesity agent, anti-inflammatory agent, brain function improver, liver function improver, bone strengthener, blood sugar level improver, and muscle strengthener) 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 strengthener of the present invention, the blood sugar level improver, and the muscle strengthener 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 necessary. However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond.

[0029] <<Compound Represented by General Formula (1)>> Examples of the compound represented by general formula (1) include compounds represented by the above R １ Mangiferin represented by the following structural formula (1), wherein R is a group represented by the general formula (2), １ and norathyriol represented by the following structural formula (2) in which is H. These may be used alone or in combination of two or more.

[0030] Mangiferin, represented by the structural formula (1), is a C-glycoside that is abundantly found in plants such as mango, Salacia, Hercampuri, etc. C-glycoside is extremely stable because the carbon of the sugar is bonded to the carbon of the compound via a carbon-carbon bond.

[0031] The mangiferin may be a commercially available product, may be prepared from a plant by a known method, or may be produced by organic synthesis by a known method. The mangiferin may be purified, or may be unpurified or crudely purified, which is prepared from a plant and contains components other than mangiferin.

[0032] Commercially available mangiferin products include, for example, M3547 (lot number: SLBQ6689V, manufactured by SIGMA).

[0033] -Norathyriol- Norathyriol represented by the structural formula (2) is the aglycone of mangiferin.

[0034] The norathyriol may be a commercially available product or may be produced by a known method. In addition, the norathyriol may be purified, or may be an unpurified or crude product containing components other than norathyriol.

[0035] Commercially available products of norathyriol include, for example, ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA).

[0036] The method for producing norathyriol is not particularly limited and can be appropriately selected from known methods, for example, a chemical method, a microbial conversion method using a microorganism, etc. Among these, the method for producing norathyriol is preferably a microbial conversion method from an environmental viewpoint.

[0037] Examples of the chemical method include organic synthesis and decomposition using an acid catalyst.

[0038] Examples of the microbial conversion method include the use of 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), Bacillus sp. and a method of converting mangiferin to norathyriol using a microorganism such as Bacillus sp. KM7-1 strain (see JP 2022-001026 A). Among these, the microbial conversion method using Bacillus sp. KM7-1 strain is preferred because it allows for simple, efficient, safe, and environmentally friendly production of norathyriol from mangiferin.

[0039] <<Other Components>> The other components in the anti-obesity agent, anti-inflammatory agent, brain function improver, liver function improver, bone strengthening agent, blood sugar level improving agent, and muscle strengthening agent are not particularly limited and can be appropriately selected depending on the purpose, as long as 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, UV absorbers, surfactants, thickeners, alcohols, powder components, colorants, aqueous components, water, skin nutrients, etc. These may be used alone or in combination of two or more.

[0040] The content of the other ingredients in the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthening agent, the blood sugar level improving agent, and the muscle strengthening agent is not particularly limited, and can be selected appropriately depending on the purpose, as long as it does not impair the effects of the present invention.

[0041]

[0039] The following describes one embodiment of the action 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 strengthening agent of the present invention, the blood glucose level improving agent of the present invention, and the muscle strengthening agent of the present invention. Note that the present invention is not limited to the following embodiment, and can be modified within the scope of those skilled in the art, such as other embodiments, additions, modifications, or deletions, and any aspect is within the scope of the present invention as long as it exhibits the action and effect of the present invention.

[0042] <Anti-obesity agent> The compound represented by the general formula (1), which is the active ingredient of the anti-obesity agent of the present invention, has at least one action selected from the group consisting of an α-glucosidase activity inhibitory action and a lipase activity inhibitory action, and can be used as the active ingredient of the anti-obesity agent by utilizing these actions.

[0043] Therefore, the anti-obesity agent has at least one action selected from the group consisting of an α-glucosidase activity inhibitory action and a lipase activity inhibitory action.

[0044] α-Glucosidase is an enzyme that catalyzes the hydrolysis of α-1,4-glucosidic bonds in sugars, and is a digestive enzyme expressed as a membrane enzyme in small intestinal epithelial cells in mammals. Among α-glucosidases, the one that breaks down maltose into glucose is called maltase, and the one that breaks down sucrose into glucose is called sucrase. As such, α-glucosidase is involved in the metabolism of carbohydrates and fats in the body, and inhibiting its activity can have an anti-obesity effect.

[0045] Lipase is an enzyme that hydrolyzes the ester bonds that make up lipids, and in mammals, it is synthesized in the pancreas and secreted into pancreatic juice as a digestive enzyme that hydrolyzes triglycerides (neutral fats). As lipase is thus involved in fat metabolism in the body, inhibiting its activity can have an anti-obesity effect.

[0046] The fact that the compound represented by the general formula (1) has at least one of an excellent α-glucosidase activity inhibitory effect and an excellent lipase activity inhibitory effect and is useful as an anti-obesity agent was not previously known and is a new finding made by the present inventors.

[0047] The α-glucosidase activity inhibitory effect of the anti-obesity agent can be confirmed as being useful as an anti-obesity agent when the amount of glucose is reduced in the presence of α-glucosidase and its substrate (e.g., maltose, sucrose, etc.) when the amount of glucose is reduced in the presence of the anti-obesity agent compared to the amount of glucose in the absence of the anti-obesity agent. The amount of glucose can be measured using a commercially available kit for measuring α-glucosidase activity inhibition (e.g., Glucose CII-Test Wako, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.).

[0048] Whether the anti-obesity agent has an inhibitory effect on α-glucosidase activity in a subject can be confirmed, for example, by comparing serum glucose levels before and after administration of the anti-obesity agent to the subject. Specifically, if the serum glucose level is measured before and after administration of the anti-obesity agent to the subject, and the serum glucose level after administration of the anti-obesity agent is lower than the serum glucose level before administration, it can be determined that the anti-obesity agent has an inhibitory effect on α-glucosidase activity.

[0049] The lipase activity inhibitory effect of the anti-obesity agent can be confirmed to be effective as an anti-obesity agent when, in the presence of lipase and its substrate (e.g., dimercaprol tributyrate (BALB)), the amount of dimercaprol (BAL; a hydrolysate of BALB) is reduced when the anti-obesity agent is added compared to the amount of dimercaprol when the anti-obesity agent is not added. The BAL amount can be measured using a commercially available lipase activity measurement reagent (e.g., Lipase Kit S, manufactured by Sumitomo Bakelite Co., Ltd.).

[0050] The content of the compound represented by general formula (1) in the 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 purpose, but the content of mangiferin in the anti-obesity agent is preferably 100 μmol / L or more, more preferably 200 μmol / L or more, based on the total amount of the anti-obesity agent.In addition, the content of norathyriol in the anti-obesity agent is preferably 100 μmol / L or more, more preferably 200 μmol / L or more, based on the total amount of the anti-obesity agent.

[0051] The anti-obesity agent may be the compound represented by the general formula (1) itself.In addition, the content ratio of mangiferin and norathyriol in the anti-obesity agent is not particularly limited, and it may contain only one of them, or may contain two kinds at a content ratio that is suitably selected.In addition, the content of the compound represented by the general formula (1) in the anti-obesity agent is preferably as high as possible, and its upper limit is not particularly limited, and it can be suitably selected according to purpose.

[0052] The present invention also includes an α-glucosidase activity inhibitor containing the compound represented by the general formula (1) as an active ingredient, and a lipase activity inhibitor containing the compound represented by the general formula (1) as an active ingredient.

[0053] <Anti-inflammatory Agent> The compound represented by the general formula (1), which is the active ingredient of the anti-inflammatory agent of the present invention, has an inhibitory effect on the release of hexosaminidase and prostaglandin E2 (PGE ２ ) production inhibitory activity, and these activities can be utilized to use the compound as an active ingredient of the anti-inflammatory agent.

[0054] Therefore, the anti-inflammatory agent has the effect of inhibiting the release of hexosaminidase and PGE ２ The inhibitory effect on the production of steroid hormones is at least one selected from the group consisting of:

[0055] Hexosaminidase is an enzyme that hydrolyzes N-acetyl-D-hexosaminide to produce N-acetyl-D-hexosamine residues, and is localized in lysosomes in mammals. It is known that hexosaminidase is released simultaneously with the release of histamine, and that inhibiting the release of hexosaminidase can also inhibit the release of histamine. Therefore, inhibiting the release of hexosaminidase can exert an anti-inflammatory effect.

[0056] PGE ２ PGE is a physiologically active substance biosynthesized from arachidonic acid, an unsaturated fatty acid. ２ The physiological functions of PGE are known to be fever, pain, vasodilation, and childbirth. ２ By suppressing the production of , an anti-inflammatory effect can be achieved.

[0057] The compound represented by the general formula (1) has an excellent hexosaminidase release inhibitory effect and an excellent PGE ２ It was not previously known that the compound has at least one of the effects of inhibiting the production of inflammatory cytokines and is useful as an anti-inflammatory agent, and this is a new discovery made by the present inventors.

[0058] The hexosaminidase release inhibitory effect of the anti-inflammatory agent can be measured by measuring the absorbance at 415 nm of p-nitrophenol (PNP), which is liberated when the agent reacts with p-nitrophenyl N-acetyl β-D-glucosaminide (p-NAG), a substrate for hexosaminidase, in the presence of hexosaminidase. That is, a lower absorbance indicates greater inhibition of hexosaminidase release. Specifically, when cells, preferably basophilic leukemia cells, are cultured in the presence of the anti-inflammatory agent and in the absence of the anti-inflammatory agent, the culture supernatant obtained is reacted with p-NAG. If the absorbance of PNP obtained from the culture supernatant obtained from the culture in the presence of the anti-inflammatory agent is lower than the absorbance of PNP obtained from the culture in the absence of the anti-inflammatory agent, the anti-inflammatory agent can be confirmed to have a hexosaminidase release inhibitory effect and to be useful as an anti-inflammatory agent.

[0059] The ability of the anti-inflammatory agent to inhibit hexosaminidase release in a subject can be confirmed, for example, by comparing serum hexosaminidase activity before and after administration of the anti-inflammatory agent to a subject. Specifically, if the serum hexosaminidase activity after administration of the anti-inflammatory agent to a subject is reduced compared to the serum hexosaminidase activity before administration, it can be confirmed that the anti-inflammatory agent has an ability to inhibit hexosaminidase release and is useful as an anti-inflammatory agent. Serum hexosaminidase activity can be measured, for example, using a commercially available hexosaminidase activity measurement kit (e.g., Beta Hexosaminidase Activity Assay Kit, manufactured by Cosmo Bio Co., Ltd.).

[0060] The anti-inflammatory agent PGE ２ The production inhibitory effect is the same as that of PGE when the anti-inflammatory agent is not added. ２ When the anti-inflammatory agent was added, the PGE ２ When the amount of PGE2 is decreased, the anti-inflammatory agent ２ It can be confirmed that the PGE2 has a production inhibitory effect and is useful as an anti-inflammatory agent. ２The amount is commercially available PGE ２ A kit for measuring the amount of PGE ２ The measurement can be performed using an EIA Kit (manufactured by Cayman Chemical Co.).

[0061] The anti-inflammatory agent is a PGE inhibitor for a subject. ２ The anti-inflammatory agent has a production inhibitory effect, for example, by measuring the PGE production before and after administration to a subject. ２ This can be confirmed by comparing the amount of PGE produced in a sample such as serum, saliva, urine, or blood before and after administration of the anti-inflammatory agent to a subject. ２ The amount of PGE produced in the sample before and after administration of the anti-inflammatory agent was measured. ２ The amount of PGE produced in the sample after administration of the anti-inflammatory agent is compared to the amount of PGE produced. ２ If the production is decreased, the anti-inflammatory agent is PGE ２ It can be judged that it has a production inhibitory effect.

[0062] The content of the compound represented by the general formula (1) in the anti-inflammatory agent is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0063] In particular, from the viewpoint of the hexosaminidase release inhibitory effect of the anti-inflammatory agent, the content of norathyriol in the 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, relative to the total amount of the anti-inflammatory agent. Note that, from the viewpoint of the hexosaminidase release inhibitory effect, the higher the content of norathyriol in the anti-inflammatory agent, the better, and its upper limit is not particularly limited and can be appropriately selected depending on the purpose.

[0064] Also, PGE ２ From the viewpoint of the production inhibitory effect, the content of mangiferin in the 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, relative to the total amount of the anti-inflammatory agent. ２From the viewpoint of the production inhibitory effect, the content of norathyriol in the 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, relative to the total amount of the anti-inflammatory agent. ２ From the viewpoint of the production-inhibiting effect, the higher the amount, the better, and there is no particular upper limit, which can be appropriately selected depending on the purpose.

[0065] In addition, the anti-inflammatory agent may be the compound represented by the general formula (1) itself.In addition, the content ratio of mangiferin and norathyriol in the anti-inflammatory agent is not particularly limited, and it may contain only one of them, or may contain two kinds at a content ratio selected appropriately, but from the viewpoint of the hexosaminidase release inhibitory effect of the anti-inflammatory agent, it is preferable to contain norathyriol.In addition, the PGE ２ From the viewpoint of the production inhibitory effect, it is preferable to contain mangiferin and norathyriol, and it is more preferable to contain norathyriol.

[0066] The present invention also provides a hexosaminidase release inhibitor containing the compound represented by the general formula (1) as an active ingredient, and a PGE inhibitor containing the compound represented by the general formula (1) as an active ingredient. ２ Also included are production inhibitors.

[0067] <Brain function improver> The compound represented by the general formula (1), which is an active ingredient of the brain function improver of the present invention, has at least one action selected from the group consisting of an action of promoting cell proliferation in astrocytes, an action of promoting mRNA expression of aquaporin 4 (AQP4) in astrocytes, an action of suppressing tumor necrosis factor (TNF-α) production in microglia, an action of suppressing the expression of genes related to inflammation-inducing factors in microglia, and an action of increasing the expression of genes related to inflammation-suppressing factors in microglia, and can be used as an active ingredient of the brain function improver by utilizing these actions.

[0068] Therefore, the brain function improver has at least one action selected from the group consisting of an action of promoting cell proliferation in astrocytes, an action of promoting aquaporin 4 (AQP4) mRNA expression in astrocytes, an action of suppressing TNF-α production in microglia, an action of suppressing the expression of genes related to inflammation-inducing factors in microglia, and an action of increasing the expression of genes related to inflammation-inhibiting factors in microglia.

[0069] As mentioned above, it is known that cerebrospinal fluid (CSF) and perivascular spaces flowing through astrocytes, a type of glial cell, contribute to the removal of protein waste products, and that AQP4, a water channel highly expressed in astrocytes, significantly contributes to the flow of cerebrospinal fluid, etc. Therefore, promoting astrocyte proliferation and / or promoting AQP4 mRNA expression can improve brain function.

[0070] Furthermore, as described above, when activated, microglia, a type of glial cell, increase the production of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, etc.), which can cause nerve damage. Therefore, suppressing the production of these inflammatory cytokines in microglia and / or suppressing the expression of inflammation-related genes can improve brain function.

[0071] In the present invention, the inhibitory effect of the brain function improver on the expression of an inflammation-inducing factor-related gene in microglia means the inhibitory effect on the expression of at least one inflammation-inducing factor-related gene, preferably mRNA, selected from the group consisting of TNF-α, iNOS, IL-6, IL-1β, IL-12, and CXCL2 in microglia.

[0072] In the present invention, the effect of increasing the expression of an inflammation suppressor-related gene in microglia by the brain function improver means the effect of increasing the expression of at least one inflammation suppressor-related gene, preferably mRNA, selected from the group consisting of IL-10 and IL-18 in microglia.

[0073] The term "increasing effect of microglia on the expression of an inflammation suppressor-related gene" means that the expression of at least one inflammation suppressor-related gene selected from the group consisting of IL-10 and IL-18 is increased when the brain function improver is applied to activated microglia, compared to the expression of at least one inflammation suppressor-related gene selected from the group consisting of IL-10 and IL-18 when the brain function improver is not applied to activated microglia.

[0074] The fact that the compound represented by the general formula (1) has at least one of an excellent effect of promoting cell proliferation in astrocytes, an excellent effect of promoting AQP4 mRNA expression in astrocytes, an excellent effect of suppressing TNF-α production in microglia, an excellent effect of suppressing the expression of genes related to inflammation-inducing factors in microglia, and an excellent effect of increasing the expression of genes related to inflammation-inducing factors in microglia, and is useful as a brain function improver was completely unknown in the past, and is a new finding by the present inventors.

[0075] The astrocyte cell proliferation promoting effect of the brain function enhancer can be confirmed as being useful as a brain function enhancer when the number of astrocytes after addition of the brain function enhancer is increased compared to the number of astrocytes before addition of the brain function enhancer. The number of astrocytes can be measured using an MTT assay.

[0076] The brain function enhancer's effect of promoting AQP4 mRNA expression in astrocytes can be confirmed as being useful as a brain function enhancer when the expression level of AQP4 mRNA in astrocytes after addition of the brain function enhancer is increased compared to the expression level of AQP4 mRNA in astrocytes before addition of the brain function enhancer. The expression level of AQP4 mRNA in astrocytes can be measured using a two-step RT-PCR method.

[0077] The inhibitory effect of the brain function enhancer on microglial TNF-α production can be confirmed by comparing the amount of TNF-α produced by microglia after the addition of the brain function enhancer with the amount of TNF-α produced by microglia before the addition of the brain function enhancer, thereby confirming that the brain function enhancer has an inhibitory effect on microglial TNF-α production and is useful as a brain function enhancer. The amount of TNF-α produced by microglia can be measured using a sandwich ELISA method.

[0078] The brain function enhancer's inhibitory effect on microglial inflammatory inducer-related gene expression can be confirmed as being useful as a brain function enhancer when the expression level of the inflammatory inducer-related gene in microglia after addition of the brain function enhancer is reduced compared to the expression level of the inflammatory inducer-related gene in microglia before addition of the brain function enhancer. The expression level of the inflammatory inducer-related gene in microglia can be measured using a two-step RT-PCR method.

[0079] The brain function enhancer's effect of increasing the expression of anti-inflammatory factor-related genes in microglia can be confirmed as being useful as a brain function enhancer if the expression level of the anti-inflammatory factor-related genes is increased when the brain function enhancer is applied to activated microglia, compared to the expression level of the anti-inflammatory factor-related genes when the brain function enhancer is not applied to activated microglia. The expression level of the anti-inflammatory factor-related genes in microglia can be measured using a two-step RT-PCR method.

[0080] The content of the compound represented by the general formula (1) in the brain function enhancer is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0081] In particular, from the viewpoint of the astrocyte proliferation promoting effect of the brain function enhancer, the content of the mangiferin in the brain function enhancer is preferably 25 μ mol / L or more, more preferably 100 μ mol / L or more, based on the total amount of the brain function enhancer.In addition, from the viewpoint of the astrocyte proliferation promoting effect of the brain function enhancer, the content of the norathyriol in the brain function enhancer is more preferably 100 μ mol / L or more, based on the total amount of the brain function enhancer.In addition, from the viewpoint of the astrocyte proliferation promoting effect of the brain function enhancer, the content of the compound represented by general formula (1) in the brain function enhancer is preferably as high as possible, and its upper limit is not particularly limited, and can be appropriately selected according to purpose.

[0082] In addition, from the viewpoint of the AQP4 mRNA expression promoting effect of the brain function enhancer in astrocyte, the content of the compound represented by the general formula (1) in the brain function enhancer is preferably 6 μ mol / L or more, more preferably 25 μ mol / L or more, particularly preferably 100 μ mol / L or more, based on the total amount of the brain function enhancer.In addition, from the viewpoint of the AQP4 mRNA expression promoting effect in astrocyte, the content of norathyriol in the brain function enhancer is more preferable, and its upper limit is not particularly limited, and can be appropriately selected according to purpose.

[0083] Furthermore, from the viewpoint of the TNF-α production inhibitory effect of the brain function enhancer, the content of norathyriol in the brain function enhancer is preferably 25 μmol / L or more, and more preferably 100 μmol / L or more, relative to the total amount of the brain function enhancer. Note that, from the viewpoint of the TNF-α production inhibitory effect, the higher the content of norathyriol in the brain function enhancer, the more preferable it is, and the upper limit thereof is not particularly limited and can be appropriately selected depending on the purpose.

[0084] Furthermore, in terms of the brain function enhancer's effect of suppressing microglial inflammatory factor-related gene expression and increasing microglial inflammatory factor-related gene expression, the content of the compound represented by general formula (1) in the brain function enhancer is preferably 6 μmol / L or more, more preferably 25 μmol / L or more, and even more preferably 100 μmol / L or more, relative to the total amount of the brain function enhancer. Note that, in terms of the effect of suppressing microglial inflammatory factor-related gene expression and increasing microglial inflammatory factor-related gene expression, the content of the compound represented by general formula (1) in the brain function enhancer is preferably as high as possible, and the upper limit is not particularly limited and can be appropriately selected depending on the purpose.

[0085] In addition, the brain function enhancer may be the compound itself represented by the general formula (1).In addition, the content ratio of mangiferin and norathyriol in the brain function enhancer is not particularly limited, and the brain function enhancer may contain only one of them, or may contain two kinds at an appropriately selected content ratio, but it is preferable to contain norathyriol.

[0086] The present invention also includes an astrocyte cell proliferation promoter containing the compound represented by the general formula (1) as an active ingredient, an astrocyte aquaporin 4 (AQP4) mRNA expression promoter containing the compound represented by the general formula (1) as an active ingredient, an inhibitor of microglial TNF-α production containing the compound represented by the general formula (1) as an active ingredient, and an agent for increasing the expression of microglial inflammation suppressor-related genes containing the compound represented by the general formula (1) as an active ingredient.

[0087] <Liver function improver> The compound represented by the following general formula (1), which is the active ingredient of the liver function improver of the present invention, has at least one effect selected from the group consisting of glutathione production promoting action, ATP (adenosine triphosphate) production promoting action, and hepatocyte proliferation promoting action, and can be used as the active ingredient of the liver function improver by utilizing these effects.

[0088] Therefore, the liver function improver has at least one action selected from the group consisting of an action of promoting glutathione production, an action of promoting ATP production, and an action of promoting hepatocyte proliferation.

[0089] As described above, glutathione protects hepatocytes from various oxidative stresses in the liver, and also directly contributes to the expression of liver functions such as drug metabolism by forming conjugates with harmful substances such as drugs and reactive compounds and excreting them outside the cells. Therefore, promoting glutathione production in the liver can improve liver function.

[0090] As described above, ATP provides cells with the energy necessary for cell division and promotes cell proliferation. Therefore, promoting ATP production in the liver promotes hepatocyte proliferation, thereby improving liver function.

[0091] The fact that the compound represented by the general formula (1) has at least one of an excellent glutathione production promoting effect, an excellent ATP production promoting effect, and an excellent hepatocyte proliferation promoting effect, and is useful as a liver function improver, was not previously known and is a new discovery by the present inventors.

[0092] The glutathione production-promoting effect of the liver function improver can be confirmed as being useful as a liver function improver when the total glutathione amount is increased when the liver function improver is added compared to the total glutathione amount when the liver function improver is not added. The total glutathione amount can be calculated based on a calibration curve of glutathione standards of known concentrations prepared in advance by adding glutathione reductase to a measurement sample to cause a reaction, adding 5,5'-dithiobis(2-nitrobenzoic acid), and measuring the absorbance at a wavelength of 412 nm for 5 minutes.

[0093] The ATP production promoting effect of the liver function improver can be confirmed as being useful as a liver function improver when the amount of ATP increases when the liver function improver is added compared to the amount of ATP when the liver function improver is not added. The amount of ATP can be measured using a commercially available ATP measurement reagent (for example, a "cellular" ATP measurement reagent). ＴＭ Ver. 2, manufactured by Toyo B-Net Co., Ltd.) can be used for the measurement.

[0094] The hepatocyte proliferation-promoting effect of the liver function improver can be confirmed when the number of hepatocytes increases when the liver function improver is added compared to when the liver function improver is not added, and the liver function improver is therefore useful as a liver function improver. The number of hepatocytes can be measured by an MTT assay.

[0095] The content of the compound represented by the general formula (1) in the liver function improver is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0096] In particular, from the viewpoint of the glutathione production promoting effect of the liver function improver, the content of the norathyriol in the 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 relative to the total amount of the liver function improver.In addition, from the viewpoint of the glutathione production promoting effect, the content of the norathyriol in the liver function improver is preferably as high as possible, and its upper limit is not particularly limited, and can be suitably selected according to purpose.

[0097] In addition, from the viewpoint of the ATP production promoting effect of said liver function improver, the content of said norathyriol in said liver function improver is preferably 1 μmol / L or more, more preferably 6 μmol / L or more, even more preferably 25 μmol / L or more, particularly preferably 100 μmol / L or more, based on the total amount of said brain function improver.In addition, from the viewpoint of the ATP production promoting effect, the content of said norathyriol in said liver function improver is more preferable, and its upper limit is not particularly limited, and can be suitably selected according to purpose.

[0098] In addition, from the viewpoint of the hepatocyte proliferation promoting effect of said liver function improver, the content of said norathyriol in said liver function improver is preferably 20 μ mol / L or more, more preferably 25 μ mol / L or more, based on the total amount of said brain function improver.In addition, from the viewpoint of the hepatocyte proliferation promoting effect, the content of said norathyriol in said liver function improver is more preferably as high as possible, and its upper limit is not particularly limited, and can be suitably selected according to purpose.

[0099] The liver function improver may be the compound itself represented by the general formula (1).In addition, the content ratio of mangiferin and norathyriol in the liver function improver is not particularly limited, and the liver function improver may contain only one of them, or may contain two kinds of them at a content ratio that is suitably selected, but it is preferable to contain norathyriol.

[0100] The present invention also includes a glutathione production promoter containing a compound represented by the general formula (1) as an active ingredient, an ATP production promoter containing a compound represented by the general formula (1) as an active ingredient, and a hepatocyte proliferation promoter containing a compound represented by the general formula (1) as an active ingredient.

[0101] <Bone strengthening agent> The compound represented by the following general formula (1), which is the active ingredient of the bone strengthening agent of the present invention, has the effect of promoting type I collagen production, and this effect can be utilized to use it as the active ingredient of the bone strengthening agent.

[0102] Therefore, the bone strengthening agent has an effect of promoting type I collagen production.

[0103] As mentioned above, type I collagen is a major component of bone, and therefore, promoting the production of type I collagen in bone can have a bone strengthening effect.

[0104] The fact that the compound represented by the general formula (1) has an excellent type I collagen production promoting effect and is useful as a bone strengthening agent was not previously known, and is a new discovery made by the present inventors.

[0105] The type I collagen production promoting effect of the bone strengthening agent can be confirmed to be effective as a bone strengthening agent when the amount of type I collagen after addition of the bone strengthening agent is increased compared to the amount of type I collagen before addition of the bone strengthening agent. The amount of type I collagen can be measured by sandwich ELISA.

[0106] The content of the compound represented by the general formula (1) in the bone strengthening agent is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0107] In particular, from the viewpoint of the type I collagen production promoting effect of the bone strengthening agent, the content of norathyriol in the bone strengthening agent is preferably 6 μmol / L or more, more preferably 25 μmol / L or more, relative to the total amount of the bone strengthening agent. Note that, from the viewpoint of the type I collagen production promoting effect, the higher the content of norathyriol in the bone strengthening agent, the better, and there is no particular upper limit, which can be appropriately selected depending on the purpose.

[0108] The bone strengthening agent may be the compound itself represented by the general formula (1).In addition, the content ratio of mangiferin and norathyriol in the bone strengthening agent is not particularly limited, and the bone strengthening agent may contain only one of them, or may contain two kinds of them in a content ratio suitably selected, but it is preferable to contain norathyriol.

[0109] The present invention also includes a type I collagen production promoter containing the compound represented by the general formula (1) as an active ingredient.

[0110] <Blood Glucose 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 an inhibitory effect on dipeptidyl peptidase IV (DPPIV) activity, and this effect can be utilized to use it as the active ingredient of the blood glucose level-improver.

[0111] Therefore, the blood glucose level-improving agent has an inhibitory effect on DPPIV activity.

[0112] As described above, DPPIV is an enzyme that degrades incretin, a hormone that promotes insulin secretion from pancreatic β cells in a blood glucose-dependent manner, suppresses glucagon secretion from pancreatic α cells, lowers blood pressure, etc. Therefore, inhibiting the enzymatic activity of DPPIV can improve blood glucose levels.

[0113] The fact that the compound represented by the general formula (1) has an excellent DPPIV activity inhibitory effect and is useful as a blood glucose level improving agent was not previously known at all, and is a new finding made by the present inventors.

[0114] The DPPIV activity inhibitory effect of the blood glucose level-improving agent can be confirmed to be effective as a blood glucose level-improving agent when the DPPIV activity inhibition is increased with the addition of the blood glucose level-improving agent compared to the DPPIV activity without the addition of the blood glucose level-improving agent. The DPPIV activity can be determined by reacting with an incretin or the like (e.g., Gly-Pro-p-NA.Tos[GPNT] solution (manufactured by Peptide Institute, Inc.)), which is a substrate of DPPIV, and measuring the absorbance of p-NA (p-nitroanilide) released from the substrate.

[0115] The content of the compound represented by the general formula (1) in the blood glucose level-improving agent is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0116] In particular, from the viewpoint of the DPPIV activity inhibitory effect of the blood glucose level improving agent, the content of the mangiferin in the blood glucose level improving agent 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, relative to the total amount of the blood glucose level improving agent.In addition, from the viewpoint of the DPPIV activity inhibitory effect, the content of the mangiferin in the blood glucose level improving agent is preferably as high as possible, and its upper limit is not particularly limited, and can be suitably selected according to purpose.

[0117] Furthermore, from the viewpoint of the DPPIV activity inhibitory effect of the blood glucose level improving agent, the content of norathyriol in the blood glucose level improving agent 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, relative to the total amount of the blood glucose level improving agent.

[0118] The blood glucose level improving agent may be the compound itself represented by the general formula (1). The content ratio of mangiferin and norathyriol in the blood glucose level improving agent is not particularly limited, and the agent may contain only one of them, or may contain both of them at an appropriately selected content ratio.

[0119] The present invention also includes a DPPIV activity inhibitor containing the compound represented by the general formula (1) as an active ingredient.

[0120] <Muscle strengthening agent> The compound represented by the following general formula (1), which is the active ingredient of the muscle strengthening agent of the present invention, has the effect of promoting myoblast proliferation, and this effect can be utilized to use it as the active ingredient of the muscle strengthening agent.

[0121] Therefore, the muscle strengthening agent has a myoblast proliferation promoting effect.

[0122] As mentioned above, myoblasts are cells that make up muscles, and therefore, promoting the proliferation of myoblasts in muscles can have a muscle strengthening effect.

[0123] The fact that the compound represented by the general formula (1) has an excellent myoblast proliferation promoting effect and is useful as a muscle strengthening agent was not previously known, and is a new discovery made by the present inventors.

[0124] The muscle-strengthening agent has the effect of promoting myoblast proliferation when the number of myoblasts after the addition of the muscle-strengthening agent is increased compared to the number of myoblasts before the addition of the muscle-strengthening agent. The number of myoblasts can be measured by the MTT assay.

[0125] The content of the compound represented by the general formula (1) in the muscle strengthening agent is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0126] In particular, from the standpoint of the muscle strengthening agent's myoblast proliferation-promoting effect, it is preferable that the content of mangiferin in the muscle strengthening agent is 1 μmol / L or more relative to the total amount of the muscle strengthening agent, 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.

[0127] In addition, the muscle strengthening agent may be the compound itself represented by the general formula (1). In addition, the content ratio of mangiferin and norathyriol in the muscle strengthening agent is not particularly limited, and the muscle strengthening agent may contain only one of them, or may contain two kinds at an appropriately selected content ratio, but it is preferable that the muscle strengthening agent contains mangiferin.

[0128] The present invention also includes a myoblast proliferation promoter containing the compound represented by the general formula (1) as an active ingredient.

[0129] The compound represented by the general formula (1) can be formulated into any dosage form, such as powder, granules, or liquid, using a pharmaceutically acceptable carrier such as dextrin or cyclodextrin, or any other auxiliary agent, according to a conventional method. In this case, examples of the auxiliary agent that can be used include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring / flavoring agents.

[0130] The anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengthening agents, blood sugar level improving agents, and muscle strengthening agents can be incorporated into other compositions (for example, oral compositions, cosmetic compositions, etc., which will be described later) and used. They can also be used as oral administration agents such as tablets, powders, capsules, granules, extracts, and syrups; parenteral administration agents such as injections, drip infusions, and suppositories; ointments, eye drops, external liquids, and patches.

[0131] The method of use 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 improving agent, and the muscle strengthening agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include oral administration, parenteral administration, and external administration.

[0132] The dosage forms of the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthening agent, the blood sugar level improving agent, and the muscle strengthening agent are not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include oral administration agents such as tablets, powders, capsules, granules, extracts, and syrups; parenteral administration agents such as injections, drip infusions, and suppositories; and external administration agents such as lotions, emulsions, creams, ointments, beauty serums, lotions, packs, jellies, lip balms, lipsticks, foundations, bath additives, soaps, body shampoos, astringents, hair tonics, hair creams, hair liquids, pomades, shampoos, and rinses.

[0133] The method for producing the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthener, the blood sugar level improver, and the muscle strengthener in any dosage form is not particularly limited, and any known method can be appropriately selected.

[0134] -Dosage and Administration- The administration method, dosage, administration site, administration period, administration interval, etc. 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 improving agent, and the muscle strengthening agent are not particularly limited and can be selected appropriately depending on the purpose.

[0135] -Uses- The anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthening agent, the blood glucose level improving agent, and the muscle strengthening agent each have excellent anti-obesity effects, excellent anti-inflammatory effects, excellent brain function improving effects, excellent liver function improving effects, excellent bone strengthening effects, excellent blood glucose level improving effects, and excellent muscle strengthening effects, and are highly safe, so they can be used in a wide range of applications, such as pharmaceuticals, quasi-drugs, foods and beverages, and cosmetics. For example, they can be suitably used as active ingredients in oral compositions and cosmetic compositions described below. In this case, the compound represented by general formula (1), preferably at least one of the compound represented by structural formula (1) and the compound represented by structural formula (2), may be blended directly, or a formulation of the compound represented by general formula (1), preferably at least one of the compound represented by structural formula (1) and the compound represented by structural formula (2), may be blended.

[0136] In addition, the anti-obesity agent, the anti-inflammatory agent, the brain function improving agent, the liver function improving agent, the bone strengthening agent, the blood sugar level improving agent, and the muscle strengthening agent can also be used as an active ingredient by blending, as necessary, another ingredient having at least one effect selected from an anti-obesity effect, an anti-inflammatory effect, a brain function improving effect, a liver function improving effect, a bone strengthening effect, a blood sugar level improving effect, and a muscle strengthening effect, together with the compound represented by general formula (1).

[0137] The anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengthening agents, blood sugar level improving agents, and muscle strengthening agents are preferably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as their respective action effects are exerted.

[0138] In addition, the anti-obesity agents, anti-inflammatory agents, brain function improving agents, liver function improving agents, bone strengthening agents, blood sugar level improving agents, and muscle strengthening agents can also be used as reagents for research into the mechanisms of action of the anti-obesity effects, anti-inflammatory effects, brain function improving effects, liver function improving effects, bone strengthening effects, blood sugar level improving effects, and muscle strengthening effects, respectively.

[0139] In addition, compounds represented by the general formula (1) for use in anti-obesity, anti-inflammation, improving brain function, improving liver function, strengthening bones, improving blood sugar levels, or strengthening muscles are also included in the scope of the present invention.

[0140] The scope of the present invention also includes use of a compound represented by the following general formula (1) in the manufacture of an anti-obesity pharmaceutical, an anti-inflammatory pharmaceutical, a pharmaceutical for improving brain function, a pharmaceutical for improving liver function, a pharmaceutical for strengthening bones, a pharmaceutical for improving blood sugar levels, or a pharmaceutical for strengthening muscles.

[0141] (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 strengthener of the present invention, the blood sugar level improver of the present invention, and the muscle strengthener of the present invention, and if necessary, further contains other ingredients.

[0142] <Anti-obesity agent, anti-inflammatory agent, brain function improver, liver function improver, bone strengthening agent, blood glucose level improving agent, and muscle strengthening agent> The content of at least one selected from the group consisting 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 improving agent, and the muscle strengthening agent in the oral composition is not particularly limited and can be appropriately selected depending on the purpose. Note that the content of at least one selected from the group consisting 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 improving agent, and the muscle strengthening agent is preferably as high as possible, and the upper limit thereof is not particularly limited and can be appropriately selected depending on the purpose.

[0143] <Other Components> The oral composition may further contain other components that are commonly used in the production of oral compositions, as needed, within the scope of not impairing the object and effects of the present invention.

[0144] <<Other Components>> The other components in the oral composition are not particularly limited and can be appropriately selected depending on the purpose. Examples include excipients, moisture-proofing agents, preservatives, strengthening agents, thickeners, emulsifiers, antioxidants, sweeteners, acidulants, seasonings, colorants, fragrances, whitening agents, moisturizers, oily components, UV absorbers, surfactants, thickeners, alcohols, powder components, coloring agents, aqueous components, and water. These components may be used alone or in combination of two or more. When used in combination with at least one selected from the group consisting of the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthener, the blood sugar level improver, and the muscle strengthener, these components may act synergistically to provide superior effects beyond those normally expected.

[0145] The content of the other components in the oral composition is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0146] -Use- Examples of the oral composition include orally administered agents and food and beverage products. Here, food and beverage products refer to products that are unlikely to be harmful to human health and are taken orally or by administration through the gastrointestinal tract in normal social life, and are not limited to administrative classifications such as food, medicine, or quasi-drug. Therefore, the food and beverage products refer to a wide range of foods and beverage products that are taken orally, including general foods, health foods (functional food and beverage products), health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims), quasi-drugs, and medicines.

[0147] The type of the oral composition is not particularly limited and can be appropriately selected depending on 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 coffee-containing soft drinks (including concentrated liquids and powders for adjusting these beverages); frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba noodles, udon noodles, vermicelli, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; confectioneries such as candy, candy, gum, chocolate, candy tablets, snacks, biscuits, jelly, jam, cream, baked goods, and bread; seafood such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oysters, saury, squid, ark shells, scallops, abalone, sea urchin, salmon roe, and tokobushi sea bream; and kamaboko and ham. processed seafood and livestock foods such as sausages and other seafood products; dairy products such as processed milk and fermented milk; oils and fats and oil-processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; condiments such as sauces and dressings; retort pouch foods such as curry, stew, oyakodon (chicken and egg rice bowl), rice porridge, rice porridge, Chinese rice bowl, pork cutlet rice bowl, tempura rice bowl, eel rice bowl, hayashi rice, oden, mapo tofu, beef bowl, meat sauce, egg soup, omelet rice, gyoza, shumai, hamburger steak, and meatballs; side dishes such as salads and pickles; health, beauty, and nutritional supplements in various forms; pharmaceuticals and quasi-drugs such as tablets, powders, capsules, granules, extracts, syrups, drinks, lozenges, and mouthwash; oral fresheners used in the oral cavity, such as mouth fresheners and breath fresheners, and toothpastes.

[0148] The method for producing the oral composition is not particularly limited, and can be appropriately selected from known methods depending on the type of the oral composition, etc.

[0149] The amount of the oral composition to be used, the period of use, the interval between uses, etc. are not particularly limited and can be appropriately selected depending on the purpose.

[0150] The oral composition of the present invention is preferably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as the respective functional effects are achieved.

[0151] The oral composition of the present invention contains at least one selected from the group consisting of the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthener, the blood glucose level improver, and the muscle strengthener, and is therefore useful in that, when orally administered, it exhibits at least one effect selected from the group consisting of an excellent anti-obesity effect, an excellent anti-inflammatory effect, an excellent brain function improving effect, an excellent liver function improving effect, an excellent bone strengthening effect, an excellent blood glucose level improving effect, and an excellent muscle strengthening effect.

[0152] (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 strengthener of the present invention, the blood sugar level improver of the present invention, and the muscle strengthener of the present invention, and further contains other ingredients as necessary.

[0153] <Anti-obesity agent, anti-inflammatory agent, brain function improver, liver function improver, bone strengthening agent, blood glucose level improver, and muscle strengthening agent> The content of at least one selected from the group consisting 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 in the cosmetic composition is not particularly limited and can be appropriately selected depending on the purpose. Note that the content of at least one selected from the group consisting 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 is preferably as high as possible, and the upper limit is not particularly limited and can be appropriately selected depending on the purpose. Furthermore, the cosmetic composition may be at least one selected from the group consisting 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 itself.

[0154] <Other Components> The cosmetic composition may further contain, as needed, various main ingredients, auxiliary agents, and other ingredients that are commonly used in the production of cosmetic compositions, within a range that does not impair the purpose and effects of the present invention.

[0155] The other components in the cosmetic composition are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include astringents, disinfectants, antibacterial agents, ultraviolet absorbers, cell activators, oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, and fragrances. These may be used alone or in combination of two or more. When used in combination with at least one selected from the group consisting of anti-obesity agents, anti-inflammatory agents, brain function improvers, liver function improvers, bone strengtheners, blood sugar level improvers, and muscle strengtheners, these components may act synergistically to provide superior effects beyond those normally expected.

[0156] The content of the other components in the cosmetic composition is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0157] -Use- The use of the cosmetic composition is not particularly limited and can be appropriately selected from the uses of general cosmetic compositions. Examples include skin cosmetic compositions such as lotion, emulsion, cream, ointment, serum, lotion, pack, jelly, lip balm, lipstick, foundation, bath additive, soap, and body shampoo; and scalp cosmetic compositions such as astringent, hair tonic, hair cream, hair liquid, pomade, shampoo, and conditioner.

[0158] The cosmetic composition may be any cosmetic composition containing at least one selected from the group consisting 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 improving agent, and the muscle strengthening agent, in a manner that does not interfere with the activity of the agent, or may be a cosmetic composition containing at least one selected from the group consisting 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 improving agent, and the muscle strengthening agent as a main ingredient.

[0159] The method for producing the cosmetic composition is not particularly limited, and can be appropriately selected from known methods depending on the type of the cosmetic composition.

[0160] The amount of the cosmetic composition to be used, the period of use, the interval between uses, etc. are not particularly limited and can be appropriately selected depending on the purpose.

[0161] The cosmetic composition of the present invention is suitable for use on humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as the respective functional effects are achieved.

[0162] The cosmetic composition of the present invention contains at least one selected from the group consisting of the anti-obesity agent, the anti-inflammatory agent, the brain function improver, the liver function improver, the bone strengthener, the blood sugar level improving agent, and the muscle strengthener, and is therefore useful in that, when applied to the skin, it exhibits at least one effect selected from the group consisting of an excellent anti-obesity effect, an excellent anti-inflammatory effect, an excellent brain function improving effect, an excellent liver function improving effect, an excellent bone strengthening effect, an excellent blood sugar level improving effect, and an excellent muscle strengthening effect.

[0163] The present invention will be specifically explained below with reference to test examples, but the present invention is not limited to these test examples.

[0164] (Test Example 1: α-Glucosidase Activity Inhibitory Action Test) - Preparation of Test Sample Solution - For mangiferin as a test sample, a solution of M3547 (lot number: SLBQ6689V, manufactured by SIGMA) dissolved in dimethyl sulfoxide (DMSO) was used. For norathyriol as a test sample, a solution of ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) dissolved in DMSO was used.

[0165] - Preparation of crude enzyme solution - α-glucosidase was prepared by suspending 1 g of rat-derived intestinal acetone powder (I1630, manufactured by SIGMA) in 10 mL of 0.1 mol / L phosphate buffer (pH 7.0) (hereinafter, sometimes referred to as "PB") and stirring at 4°C for 1 hour. After centrifugation at 3,500 rpm for 15 minutes, the resulting supernatant was used as a crude enzyme solution.

[0166] - Measurement of test sample solution - 65 μL of PB solution, 30 μL of crude enzyme solution, and 5 μL of test sample solution were added to a 48-well plate. The test sample solutions were added so as to achieve the final concentrations shown in Tables 1 and 2 below. To this, 400 μL of 10 mmol / L maltose PB solution or 20 mmol / L sucrose PB solution was added as a substrate, and the mixture was incubated at 37°C for 30 minutes. After the reaction, the mixture was immersed in boiling water for 2 minutes to stop the reaction. After cooling on ice, the amount of glucose produced by decomposition was measured using a Glucose CII-Test Wako (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.).

[0167] - Measurement of test sample solution blank - The glucose amount was measured in the same manner as in the measurement of the test sample solution, except that 400 μL of substrate was not added in the measurement of the test sample solution, and 400 μL of PB solution was added instead of the substrate.

[0168] - Measurement of control solution - The glucose amount was measured in the same manner as in the measurement of the test sample solution, except that 5 μL of test sample solution was not added, but 5 μL of DMSO was added.

[0169] - Measurement of control solution blank - The glucose amount was measured in the same manner as in the measurement of the test sample solution, except that 5 μL of test sample solution was not added, but 5 μL of DMSO was added, and further, 400 μL of substrate was not added, but 400 μL of PB solution was added instead of the substrate.

[0170] - Calculation of α-glucosidase activity inhibition rate - Based on the measured values ​​obtained from the measurement of the test sample solution, the measurement of the test sample solution blank, the measurement of the control solution, and the measurement of the control solution blank, the α-glucosidase activity inhibition rate was calculated using the following formula (1): α-glucosidase activity inhibition rate (%) = {1 - (A - B) / (C - D)} x 100 ... formula (1) In the formula (1), "A", "B", "C", and "D" are as follows: A: Amount of glucose in the test sample solution (with test sample and substrate added) B: Amount of glucose in the test sample solution blank (with test sample and no substrate added) C: Amount of glucose in the control solution (without test sample and substrate added) D: Amount of glucose in the control solution blank (without test sample and no substrate added)

[0171] <Results> α-Glucosidase is an enzyme that has maltase activity, which breaks down maltose into glucose, and sucrase activity, which breaks down sucrose into glucose. The α-glucosidase (maltase) activity inhibition rate when maltose was used as a substrate is shown in Table 1 below, and the α-glucosidase (sucrase) activity inhibition rate when sucrose was used as a substrate is shown in Table 2 below. Mangiferin was found to have inhibitory effects on maltase activity and sucrase activity. Furthermore, norathyriol was found to have inhibitory effects on sucrase activity.

[0172]

[0173]

[0174] (Test Example 2: Lipase activity inhibitory effect test) <Test method> The porcine pancreatic lipase activity inhibitory effect test was carried out by the following method using a lipase activity measurement reagent, Lipase Kit S (manufactured by Sumitomo Bakelite Co., Ltd.).

[0175] - Preparation of test sample solution - For mangiferin as a test sample, a solution of M3547 (lot number: SLBQ6689V, manufactured by SIGMA) dissolved in PBS(-) was used. For norathyriol as a test sample, a solution of ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) dissolved in PBS(-) was used.

[0176] - Preparation of lipase solution - Porcine pancreatic lipase (manufactured by SIGMA) was dissolved in PBS(-) to a concentration of 0.03 mg / mL to prepare a lipase solution.

[0177] - Measurement of test sample solution - 10 μL of test sample solution, 250 μL of color-developing solution, 10 μL of lipase solution, and 5 μL of esterase inhibitor were added to a 48-well plate and pre-incubated at 30°C for 5 minutes while shielded from light, after which 25 μL of substrate solution was added to initiate the reaction. The test sample solution was added to give the final concentration shown in Table 3 below. After the reaction was allowed to proceed at 30°C for 30 minutes while shielded from light, 500 μL of reaction stop solution was added to stop the reaction. After the reaction was stopped, the absorbance at a wavelength of 412 nm was measured.

[0178] - Measurement of test sample solution blank - 10 μL of test sample solution, 250 μL of color-developing solution, 10 μL of lipase solution, and 5 μL of esterase inhibitor were added to a 48-well plate and pre-incubated at 30°C for 5 minutes while shielded from light. The test sample solution was added so as to give the final concentrations shown in Table 3 below. After the reaction was carried out at 30°C for 30 minutes while shielded from light, 500 μL of reaction stop solution was added to stop the reaction. After the reaction was stopped, 25 μL of substrate solution was added, and the absorbance at a wavelength of 412 nm was measured.

[0179] - Measurement of control solution - Measurement was carried out in the same manner as in the measurement of the test sample solution, except that 10 μL of the test sample solution was replaced with 10 μL of PBS(-).

[0180] - Measurement of control solution blank - 10 μL of PBS(-), 250 μL of color-developing solution, 10 μL of lipase solution, and 5 μL of esterase inhibitor were added to a 48-well plate and pre-incubated at 30°C for 5 minutes while shielding from light. After reacting at 30°C for 30 minutes while shielding from light, the reaction was stopped by adding 500 μL of reaction stop solution. After stopping the reaction, 25 μL of substrate solution was added, and the absorbance at a wavelength of 412 nm was measured.

[0181] - Calculation of Lipase Activity Inhibition Rate - Based on the absorbances obtained by measuring the test sample solution, the test sample solution blank, the control solution, and the control solution blank, the lipase activity inhibition rate was calculated using the following formula (2): Lipase Activity Inhibition Rate (%) = {1 - (A - B) / (C - D)} x 100 ... formula (2) In formula (2), "A", "B", "C", and "D" are as follows: A: absorbance at 412 nm of the test sample solution (with test sample and substrate added) B: absorbance at 412 nm of the test sample solution blank (with test sample added and substrate added after stopping the reaction) C: absorbance at 412 nm of the control solution (without test sample added and substrate added) D: absorbance at 412 nm of the control solution blank (without test sample added and substrate added after stopping the reaction)

[0182] <Results> The lipase activity inhibition rates are shown in the following Table 3. Both mangiferin and norathyriol were found to have an inhibitory effect on lipase activity.

[0183]

[0184] (Test Example 3: Hexosaminidase release inhibitory activity test) <Test method> - Preparation of test sample solution - As the test sample, mangiferin was used as a solution obtained by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in a Siraganian buffer solution (pH 7.2). As the test sample, norathyriol was used as a solution obtained by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in a Siraganian buffer solution (pH 7.2). The Siraganian buffer solution contained 119 mM NaCl, 5 mM KCl, 0.4 mM MgCl. ２ , 1 mM CaCl ２ , 40 mM NaOH, 25 mM PIPES, 5.6 mM glucose, and 0.1% by volume of BSA were mixed.

[0185] - Pre-culture of rat basophilic leukemia cells - Rat basophilic leukemia cells (RBL-2H3) were cultured in S-MEM (GIBCO) containing 15% by volume of fetal bovine serum (FBS), and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 4.0 × 10 ５ The cells were diluted with 15% by volume FBS-containing S-MEM to a concentration of 100 cells / mL, and DNP-specific IgE (manufactured by SIGMA) was added to a final concentration of 0.5 μg / mL. 100 μL of the solution was then seeded into a 96-well plate per well and incubated at 37°C and 5% CO ２ After incubation, the medium was removed and the cells were washed twice with 100 μL of Shiraganian buffer.

[0186] - Measurement of test sample solution - 30 μL of Shiraganian buffer solution and 10 μL of test sample solution were added to each well of pre-cultured and washed rat basophilic leukemia cells (RBL-2H3) to the final concentrations shown in Table 4 below, and the mixture was allowed to stand at 37°C for 10 minutes. Then, 10 μL of DNP-BSA solution prepared by diluting DNP-BSA (manufactured by LSL Co., Ltd.) with Shiraganian buffer to a concentration of 400 ng / mL was added, and the mixture was allowed to stand at 37°C for 15 minutes to release hexosaminidase. The 96-well plate was then placed on ice to stop the release of hexosaminidase. 10 μL of cell supernatant from each well and 10 μL of p-nitrophenyl N-acetyl β-D-glucosaminide (p-NAG) solution diluted with 0.1 mol / L citrate buffer to a concentration of 1 mmol / L were added to a new 96-well plate and reacted at 37°C for 1 hour. After the reaction was completed, each well was added with 0.1 mol / L Na ２ CO ３ / NaHCO ３ 250 μL of the mixed aqueous solution was added, and the absorbance at wavelengths of 415 nm and 650 nm was measured, and the absorbance at wavelength 650 nm was subtracted from the absorbance at wavelength 415 nm to calculate the absorbance.

[0187] - Measurement of test sample solution blank - When measuring the test sample solution, the absorbance at wavelengths of 415 nm and 650 nm was measured in the same manner as for the test sample solution, except that 10 μL of p-NAG solution was not added and 10 μL of citrate buffer was added instead of p-NAG solution, and the value was calculated by subtracting the absorbance at wavelength 650 nm from the absorbance at wavelength 415 nm.

[0188] - Measurement of control solution - The absorbance at wavelengths of 415 nm and 650 nm was measured in the same manner as in the measurement of the test sample solution, except that 10 μL of test sample solution was not added and 10 μL of Silagahanian buffer was added instead of the test sample solution, and a value was calculated by subtracting the absorbance at a wavelength of 650 nm from the absorbance at a wavelength of 415 nm.

[0189] - Measurement of control solution blank - When measuring the test sample solution, 10 μL of test sample solution and 10 μL of p-NAG solution were not added, and 10 μL of Silagahanian buffer was added instead of the test sample solution, and 10 μL of 0.1 M citrate buffer was added instead of the p-NAG solution. The absorbance at wavelengths of 415 nm and 650 nm was measured in the same manner as in the measurement of the test sample solution, and the value was calculated by subtracting the absorbance at wavelength 650 nm from the absorbance at wavelength 415 nm.

[0190] - Calculation of hexosaminidase release inhibition rate - Based on the absorbance difference [(absorbance at a wavelength of 415 nm) - (absorbance at a wavelength of 650 nm)] obtained by measuring the test sample solution, the test sample solution blank, the control solution, and the control solution blank, the hexosaminidase release inhibition rate was calculated according to the following formula (3): Hexosaminidase release inhibition rate (%) = {1 - (A - B) / (C - D)} x 100 Equation (3) In equation (3), "A" and "B" are as follows: A: absorbance difference of test sample solution (test sample added and p-NAG added) [(absorbance at a wavelength of 415 nm) - (absorbance at a wavelength of 650 nm)] B: absorbance difference of test sample solution blank (test sample added and p-NAG not added) [(absorbance at a wavelength of 415 nm) - (absorbance at a wavelength of 650 nm)] C: absorbance difference of control solution (test sample not added and p-NAG added) [(absorbance at a wavelength of 415 nm) - (absorbance at a wavelength of 650 nm)] D: Absorbance difference of control solution blank (no test sample or p-NAG added) [(absorbance at a wavelength of 415 nm) - (absorbance at a wavelength of 650 nm)]

[0191] <Results> The hexosaminidase release inhibition rate is shown in the following Table 4. Norathyriol was found to have a strong inhibitory effect on hexosaminidase release.

[0192]

[0193] (Test Example 4: PGE ２Production Inhibitory Effect Test) <Test Method> - Preparation of Test Sample Solution - For mangiferin as a test sample, a solution was used in which M3547 (lot number: SLBQ6689V, manufactured by SIGMA Corporation) was dissolved in DMEM containing 10% by volume of FBS (manufactured by Nissui Pharmaceutical Co., Ltd.; the same DMEM was used in the following test examples). For norathyriol as a test sample, a solution was used in which ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA Corporation) was dissolved in DMEM containing 10% by volume of FBS.

[0194] - Pre-culture of mouse macrophage cells - Mouse macrophage cells (RAW264.7) (obtained from DS Pharma Biomedical) were cultured in DMEM containing 10% by volume of FBS and then collected using a cell scraper. The collected cells were collected at a concentration of 2.0 × 10 ５ The cells were diluted with 10% FBS-containing DMEM to a concentration of 100 cells / mL, and then seeded in a 96-well plate at 100 μL per well. The cells were incubated at 37°C and 5% CO ２ After the incubation, 100 μL of DMEM containing 500 μmol / L aspirin was added to inactivate the existing COX-1 and the small amount of COX-2 expressed by acetylation, and the cells were incubated at 37°C and 5% CO ２ The cells were then cultured under PBS for 4 hours, and then washed three times with PBS(-).

[0195] - Measurement of test sample solution - 100 μL of test sample solution was added to each well of pre-cultured and washed mouse macrophage cells (RAW264.7) to give the final concentration shown in Table 5 below, and then 100 μL of lipopolysaccharide (LPS, E. coli O111; B4, manufactured by DIFCO) dissolved in DMEM containing 10% by volume of FBS to a final concentration of 1 μg / mL was added, and the cells were incubated at 37°C and 5% CO ２ After the incubation, the amount of prostaglandin E2 in the culture supernatant of each well was measured by PGE ２ Quantitation was carried out using an EIA kit (manufactured by Cayman Chemical Co.).

[0196] - Measurement of control (with LPS stimulation) - A test sample solution blank was measured in the same manner as the measurement of the test sample solution, except that 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 10% by volume of FBS.

[0197] - Measurement of control (no LPS stimulation) - The control solution was measured in the same manner as the measurement of the test sample solution, except that in the measurement of the test sample solution, 100 μL of the test sample solution and 100 μL of lipopolysaccharide dissolved in DMEM containing 10% by volume FBS at a final concentration of 1 μg / mL were replaced with 200 μL of DMEM containing 10% by volume FBS.

[0198] -PGE ２ Calculation of the production inhibition rate - Based on the quantitative values ​​obtained by measuring the test sample solution, measuring the test sample solution blank, and measuring the control solution, the PGE production inhibition rate was calculated using the following formula (4). ２ The production inhibition rate was calculated. ２ Production inhibition rate (%) = {1 - (A - C) / (B - C)} x 100 Equation (4) In the above equation (4), "A", "B", and "C" are as follows: A: Amount of prostaglandin E2 in the test sample solution (with test sample added and LPS stimulation) B: Amount of prostaglandin E2 in the control (with LPS stimulation) (without test sample added and LPS stimulation) C: Amount of prostaglandin E2 in the control (without LPS stimulation) (without test sample added and without LPS stimulation)

[0199] <Results> PGE ２ The production inhibition rate is shown in Table 5 below. ２ In addition, mangiferin has a weak inhibitory effect on PGE production. ２ A production inhibitory effect was observed.

[0200]

[0201] (Test Example 5: Astrocyte proliferation promotion activity test) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution of M3547 (lot number: SLBQ6689V, manufactured by SIGMA) dissolved in DMEM containing 10% by volume of FBS was used. Furthermore, for norathyriol as a test sample, a solution of ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) dissolved in DMEM containing 10% by volume of FBS was used.

[0202] - Pre-culture of mouse-derived astrocyte culture line - Mouse-derived astrocyte culture line (C8-S) (obtained from ATCC) was cultured in DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 2.5 x 10 ４ The cells were diluted with 10% FBS-containing DMEM to a concentration of 100 cells / mL, and then seeded in a 96-well plate at 100 μL per well. The cells were incubated at 37°C and 5% CO ２ The mixture was incubated under reduced pressure for 6 hours.

[0203] - Measurement of test sample solution - 100 μL of test sample solution was added to each well of the pre-cultured mouse-derived astrocyte culture line (C8-S) to give the final concentration shown in Table 6 below, and the solution was incubated at 37°C and 5% CO ２ The cells were cultured for 4 days under 5% CO. The cell proliferation promoting activity was measured using the MTT assay. After the culture was completed, the medium was removed, and 100 μL of MTT (Dojindo Laboratories) dissolved in PBS(-) at a final concentration of 0.4 mg / mL was added to each well. ２ After culturing for 2 hours under 570 nm, the blue formazan produced in the cells was extracted with 100 μL of 2-propanol. After extraction, the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two (absorbance at a wavelength of 570 nm - absorbance at a wavelength of 650 nm) was taken as the amount of blue formazan produced.

[0204] - Measurement of control solution - The control solution was measured in the same manner as the test sample solution, except that 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 10% by volume of FBS.

[0205] - Calculation of astrocyte proliferation promotion rate - Based on the amount of blue formazan produced obtained by measuring the test sample solution and the control solution, the astrocyte proliferation promotion rate was calculated using the following formula (5): Astrocyte proliferation promotion rate (%) = A / B × 100 ... formula (5) In formula (5), "A" and "B" are as follows: A: Amount of blue formazan produced in cells in the test sample solution (when the test sample was added) B: Amount of blue formazan produced in cells in the control solution (when the test sample was not added)

[0206] <Results> The astrocyte proliferation promotion rate is shown in the following Table 6. Both norathyriol and mangiferin were found to have a significant astrocyte proliferation promotion effect.

[0207]

[0208] (Test Example 6: Test of promoting effect of AQP4 mRNA expression in astrocytes) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used. Furthermore, for norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used.

[0209] - Pre-culture of mouse-derived astrocyte culture line - Mouse-derived astrocyte culture line (C8-S) (obtained from ATCC) was cultured in DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 5.0 × 10 ４ The cells were diluted with DMEM containing 10% by volume of FBS to a concentration of 100 cells / mL, and then seeded in a 6-well plate at 2 mL per well. The mixture was then incubated at 37°C and 5% CO ２ The cells were cultured under 500°C until they became confluent.

[0210] - Measurement of test sample solution - After completion of pre-culture, the medium was removed from each well of the pre-cultured mouse-derived astrocyte culture line (C8-S), and 2 mL of test sample solution was added to each well to give the final concentration shown in Table 7 below. The solution was incubated at 37°C and 5% CO ２ The cells were cultured for 24 hours under 500°C. After the culture was completed, the culture medium was removed, and total RNA was extracted using RNeasy® Mini Kit (Qiagen). The amount of RNA was calculated from the absorbance at 260 nm, and total RNA was prepared to be 100 ng / μL. Using this total RNA as a template, the expression levels of aquaporin 4 (AQP4) and the internal standard glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA were measured. Detection was performed using a real-time PCR device (Thermal Cycler Dice® Real Time System III, Takara Bio Inc.) using PrimeScript. ＴＭ The reaction was carried out by a two-step real-time PCR (RT-PCR) reaction using RT Master Mix (Perfect Real Time, manufactured by Takara Bio Inc.) and TB Green (registered trademark) Fast qPCR Mix (manufactured by Takara Bio Inc.).

[0211] - Measurement of control solution - The control solution was measured in the same manner as the test sample solution, except that 2 mL of test sample solution was replaced with 2 mL of DMEM containing 10% by volume of FBS.

[0212] - Calculation of AQP4 mRNA expression promotion rate - The expression levels of AQP4 mRNA obtained by measurement of the test sample solution and the control solution were corrected by the expression level of GAPDH mRNA obtained in each measurement, and the AQP4 mRNA expression promotion rate was calculated using the following formula (6): AQP4 mRNA expression promotion rate (%) = A / B × 100 ... formula (6) In formula (6), "A" and "B" are as follows: A: AQP4 mRNA expression level in the test sample solution (when the test sample is added) corrected by the expression level of GAPDH mRNA B: AQP4 mRNA expression level in the control solution (when the test sample is not added) corrected by the expression level of GAPDH mRNA

[0213] <Results> The AQP4 mRNA expression promotion rate is shown in the following Table 7. As shown in the following Table 7, both norathyriol and mangiferin were found to have a significant effect of promoting AQP4 mRNA expression.

[0214]

[0215] (Test Example 7: Test of inhibitory effect on tumor necrosis factor-α (TNF-α) production by microglia) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used. For norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used.

[0216] - Pre-culture of mouse-derived microglial culture line - Mouse-derived microglial culture line (C8-B4) (obtained from ATCC) was cultured using DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 1.0 × 10 ５ The cells were diluted with 10% FBS-containing DMEM to a concentration of 100 cells / mL, and then seeded in a 96-well plate at 100 μL per well. The cells were incubated at 37°C and 5% CO ２ The cells were cultured under 500°C until they became confluent.

[0217] - Measurement of test sample solution - After completion of pre-culture, the medium was removed from each well of the pre-cultured mouse-derived microglia culture line (C8-B4), and 100 μL of the test sample solution was added to each well to achieve the final concentration shown in Table 8 below. Subsequently, 100 μL of a mixture of lipopolysaccharide (LPS, E. coli O111; B4, manufactured by SIGMA) and 5 ng / mL interferon-gamma (IFN-γ from mouse, manufactured by R&D Systems) dissolved in DMEM containing 10% by volume FBS to a final concentration of 0.5 μg / mL was added, and the wells were incubated at 37°C and 5% CO ２ After incubation, the amount of TNF-α in the culture supernatant of each well was measured by sandwich ELISA using a TNF-α monoclonal antibody (Anti-Mouse TNF-α monoclonal Ab (MM350C), Thermo Fisher Scientific) and a TNF-α monoclonal antibody (Anti-Mouse TNF-α Polyclonal Ab (P350), Thermo Fisher Scientific).

[0218] - Measurement of control solution - The control solution was measured in the same manner as the test sample solution, except that 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 10% by volume of FBS.

[0219] - Calculation of TNF-α production inhibition rate - Based on the amounts of TNF-α obtained by measuring the test sample solution and the control solution, the TNF-α production inhibition rate was calculated using the following formula (7): TNF-α production inhibition rate (%) = {(B - A) / B} x 100 ... formula (7) In formula (7), "A" and "B" are as follows: A: Amount of TNF-α in the test sample solution (when the test sample was added) B: Amount of TNF-α in the control solution (when the test sample was not added)

[0220] <Results> The TNF-α production inhibition rate is shown in the following Table 8. As shown in the following Table 8, norathyriol was found to have a significant inhibitory effect on TNF-α production.

[0221]

[0222] (Test Example 8: Test for increasing effect of mRNA expression of inflammation-related genes in microglia) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used. For norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used.

[0223] - Pre-culture of mouse-derived microglial culture line - Mouse-derived microglial culture line (C8-B4) (obtained from ATCC) was cultured using DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 1.0 × 10 ５ The cells were diluted with DMEM containing 10% by volume of FBS to a concentration of 10 cells / mL, and then seeded in a 6-well plate at 2 mL per well. The cells were incubated at 37°C and 5% CO ２ The cells were cultured under 500°C until they became confluent.

[0224] - Measurement of test sample solution - After completion of pre-culture, the medium was removed from each well of the pre-cultured mouse-derived microglia culture line (C8-B4), and 1 mL of test sample solution was added to each well to achieve the final concentration shown in Table 9 below. Subsequently, 1 mL of a mixture of lipopolysaccharide (LPS, E. coli O111; B4, manufactured by SIGMA) at a final concentration of 0.5 μg / mL and interferon-gamma (IFN-γ from mouse, manufactured by R&D Systems) at a final concentration of 5 ng / mL, both dissolved in DMEM containing 10% by volume of FBS, was added, and the wells were incubated at 37°C and 5% CO ２The cells were cultured for 24 hours under a constant temperature. After the culture was completed, the culture medium was removed, and total RNA was extracted using an RNA extraction reagent (ISOGEN II, manufactured by ISOGEN II). The amount of RNA was calculated from the absorbance at 260 nm, and total RNA was prepared to be 100 ng / μL. Using this total RNA as a template, the expression levels of mRNA for various inflammation-related genes, TNF-α, iNOS, IL-6, IL-1β, IL-12, CXCL2, IL-10, and IL-18, as well as the internal standard GAPDH, were measured. Detection was performed using a real-time PCR device (Thermal Cycler Dice® Real Time System III, manufactured by Takara Bio Inc.) using PrimeScript. ＴＭ The reaction was carried out by a two-step RT-PCR reaction using RT Master Mix (Perfect Real Time, manufactured by Takara Bio Inc.) and TB Green (registered trademark) Fast qPCR Mix (manufactured by Takara Bio Inc.).

[0225] - Measurement of control solution - The control solution was measured in the same manner as the test sample solution, except that 1 mL of test sample solution was replaced with 1 mL of DMEM containing 10% by volume of FBS.

[0226] Measurement of Unstimulated Control Solution The unstimulated control solution was measured in the same manner as the measurement of the test sample solution, except that 1 mL of the test sample solution was replaced with 1 mL of DMEM containing 10% by volume of FBS, and 1 mL of the mixture of LPS and IFN-γ was replaced with 1 mL of DMEM containing 10% by volume of FBS.

[0227] - Calculation of mRNA expression rate of inflammation-related genes - The mRNA expression levels of various inflammation-related genes 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 in each measurement, and the mRNA expression rates of various inflammation-related genes were calculated using the following formula (8): Expression rate of various inflammation-related genes mRNA (%) = A / B × 100 ... formula (8) In formula (8), "A" and "B" are as follows: A: The corrected value of the expression level of various inflammation-related gene mRNA in the test sample solution (with test sample added and stimulated with LPS and IFN-γ) or the unstimulated control solution (without test sample added and without stimulated with LPS and IFN-γ) based on the expression level of GAPDH mRNA B: The corrected value of the expression level of various inflammation-related gene mRNA in the control solution (without test sample added and stimulated with LPS and IFN-γ) based on the expression level of GAPDH mRNA

[0228] <Results> The inhibition rates of TNF-α production are shown in Tables 9 to 11 below. As shown in Tables 9 to 11 below, when comparing the blank and control, stimulation with LPS and IFN-γ increased the mRNA expression of inflammation-inducing factors TNF-α, iNOS, IL-6, IL-1β, IL-12, and CXCL2, decreased the mRNA expression of inflammation-suppressing factor IL-10, and did not change the mRNA expression of IL-18, a member of the IL-1 family. In contrast, mangiferin decreased the mRNA expression of inflammation-inducing factors TNF-α, iNOS, IL-6, IL-1β, and CXCL2, but also decreased the mRNA expression of inflammation-suppressing factor IL-10, and a decrease in the mRNA expression of IL-18 was also observed. Norathyriol concentration-dependently reduced the mRNA expression of inflammation-inducing factors TNF-α, iNOS, IL-6, IL-1β, and CXCL2, while increasing the mRNA expression of inflammation-suppressing factors IL-10 and IL-18.

[0229]

[0230]

[0231]

[0232] (Test Example 9: Test for glutathione production promoting activity) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 1% by volume of FBS was used. For norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in DMEM containing 1% by volume of FBS was used.

[0233] - Pre-culture of normal human hepatocytes - Normal human hepatocytes (hepatocytes) (obtained from DS Pharma Biomedical) were cultured in DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 1.0 x 10 ５ The cells were diluted with 10% FBS-containing DMEM to a concentration of 100 cells / mL, and then seeded in a 48-well plate at 200 μL per well. The cells were then incubated at 37°C and 5% CO ２ The mixture was incubated overnight under

[0234] - Measurement of test sample solution - After the pre-incubation was completed, 200 μL of the test sample was added to each well so as to give the final concentration shown in Table 12 below, and the cells were further incubated at 37°C and 5% CO ２ After incubation, the medium was removed from each well, and the wells were washed with 400 μL of PBS (-). ＴＭProtein was extracted from the cells using 150 μL of Mammalian Protein Extraction Reagent (Thermo Fisher Scientific). Total glutathione was quantified using 100 μL of this protein extract. Specifically, 50 μL of PB, 25 μL of 2 mmol / L NADPH (Fujifilm Wako Pure Chemical Industries, 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. The absorbance at 412 nm was measured for 5 minutes, and the OD / min was calculated. The total amount of glutathione was calculated based on a calibration curve prepared using oxidized glutathione (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.).

[0235] - Measurement of Control Solution - The control solution was measured in the same manner as the test sample solution, except that 200 μL of the test sample was replaced with 200 μL of DMEM containing 10% by volume of FBS.

[0236] - Calculation of glutathione production promotion rate - Based on the total amount of glutathione obtained by measuring the test sample solution and the control solution, the glutathione production promotion rate was calculated using the following formula (9): Glutathione production promotion rate (%) = A / B × 100 ... formula (9) In formula (9), "A" and "B" are as follows: A: Amount of glutathione in cells in the test sample solution (when the test sample was added) B: Amount of glutathione in cells in the control solution (when the test sample was not added)

[0237] <Results> The rates of promotion of glutathione production are shown in Table 12. Norathyriol was found to have a significant effect of promoting glutathione production.

[0238]

[0239] (Test Example 10: Test of ATP production promoting effect) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used. For norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in DMEM containing 10% by volume of FBS was used.

[0240] - Pre-culture of normal human hepatocytes - Normal human hepatocytes (hepatocytes) (obtained from DS Pharma Biomedical) were cultured in DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 2.0 × 10 ５ The cells were diluted with 10% FBS-containing DMEM to a concentration of 100 cells / mL, and then seeded in a 96-well plate at 100 μL per well. The mixture was incubated at 37°C and 5% CO ２ The mixture was incubated overnight under

[0241] - Measurement of test sample solution - The medium was removed from each well of pre-cultured normal human hepatocytes, and 100 μL of test sample solution was added to the wells to give the final concentration shown in Table 13 below. The cells were incubated at 37°C and 5% CO ２ The cells were cultured under the same conditions for 2 hours. The ATP production promoting effect was measured using the firefly luciferase luminescence method. That is, after the culture was completed, the amount of ATP in the cells was measured using the ATP measurement reagent ("cellular" ATP measurement reagent). ＴＭ Ver. 2, manufactured by Toyo B-Net Co., Ltd.) was added to each well in an amount of 100 μL, and after the reaction, the amount of chemiluminescence was measured.

[0242] - Measurement of control solution - The control solution was measured in the same manner as the test sample solution, except that 100 μL of the test sample solution was replaced with 100 μL of DMEM containing 10% by volume of FBS.

[0243] - Calculation of ATP production promotion rate - Based on the chemiluminescence levels obtained by measuring the test sample solution, the positive control sample solution, and the control solution, the ATP production promotion rate was calculated using the following formula (10): ATP production promotion rate (%) = A / B × 100 ... formula (10) In formula (10), "A" and "B" are as follows: A: Amount of chemiluminescence in cells with the test sample solution (when the test sample was added) B: Amount of chemiluminescence in cells with the control solution (when the test sample was not added)

[0244] <Results> The ATP production promotion rate is shown in the following Table 13. Norathyriol was found to have a significant ATP production promotion effect.

[0245]

[0246] (Test Example 11: Test of hepatocyte proliferation promoting activity) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 1% by volume of FBS was used. For norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in DMEM containing 1% by volume of FBS was used.

[0247] - Pre-culture of normal human hepatocytes - Normal human hepatocytes (hepatocytes) (obtained from DS Pharma Biomedical) were cultured in DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 1.25 x 10 ４ The cells were diluted with 10% FBS-containing DMEM to a concentration of 100 cells / mL, and then seeded in a 96-well plate at 100 μL per well. The cells were incubated at 37°C and 5% CO ２ The mixture was incubated overnight under

[0248] - Measurement of test sample solution - The medium was removed from each well of pre-cultured normal human hepatocytes (hepatocytes), and 200 μL of test sample solution was added to the wells to give the final concentration shown in Table 14 below. The wells were incubated at 37°C and 5% CO ２The cells were cultured for 3 days under 5% CO. The activity of promoting proliferation of normal human hepatocytes was measured using the MTT assay. After the culture was completed, the medium was removed, and 100 μL of MTT (Dojindo Laboratories) dissolved in PBS(-) at a final concentration of 0.4 mg / mL was added to each well. The cells were incubated at 37°C, 5% CO. ２ After culturing for 2 hours under 570 nm, the blue formazan produced in the cells was extracted with 100 μL of 2-propanol. After extraction, the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two (absorbance at a wavelength of 570 nm - absorbance at a wavelength of 650 nm) was taken as the amount of blue formazan produced.

[0249] - Measurement of control solution - The control solution was measured in the same manner as the test sample solution, except that 200 μL of the test sample solution was replaced with 200 μL of DMEM containing 10% by volume of FBS.

[0250] - Calculation of normal human hepatocyte proliferation promotion rate - Based on the amount of blue formazan produced obtained by measuring the test sample solution and the control solution, the astrocyte proliferation promotion rate was calculated using the following formula (11): Astrocyte proliferation promotion rate (%) = A / B × 100 ... formula (11) In formula (11), "A" and "B" are as follows: A: Amount of blue formazan produced in cells in the test sample solution (when the test sample was added) B: Amount of blue formazan produced in cells in the control solution (when the test sample was not added)

[0251] <Results> The normal human hepatocyte proliferation promotion rate is shown in the following Table 14. As shown in the following Table 14, norathyriol was found to have a significant effect of promoting the proliferation of normal human hepatocytes.

[0252]

[0253] Test Example 12: Test of type I collagen production promoting effect in osteoblasts <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA Corporation) in FBS-free High-DMEM (high glucose (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with 20 mmol / L HEPES, manufactured by SIGMA Corporation; in the following test examples, the same High-DMEM was used) was used. Furthermore, for norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA Corporation) in FBS-free High-DMEM was used.

[0254] - Pre-culture of human osteoblasts (SaM-1) - Human osteoblasts (SaM-1) were cultured using High-DMEM containing 10% by volume of FBS, and then harvested by trypsin treatment. The harvested cells were collected at a concentration of 6 x 10 ４ The mixture was diluted with High-DMEM containing 10% by volume of FBS to a concentration of 100 cells / mL, and then seeded in a 96-well plate at 200 μL per well. The mixture was incubated at 37°C and 5% CO ２ The cells were cultured under 5% CO₂ for 3 days.

[0255] After the pre-incubation, the wells were washed with 100 μL / well of PBS(−), and the medium was replaced with 100 μL / well of FBS-free High-DMEM. ２ After culturing for 24 hours under the conditions shown in Table 15, 100 μL of the test sample was added to each well to give the final concentration shown in Table 15 below, and the cells were incubated at 37° C., 5% CO ２ The cells were cultured for 3 days under reduced pressure. After the culture, the amount of type I collagen in the medium in each well was measured by sandwich ELISA using an anti-type I collagen polyclonal antibody (Polyclonal Antibody to Collagen Type I, manufactured by Acris). The cell viability in each well was measured by WST8 assay using Cell Counting Kit-8 (manufactured by Dojindo Laboratories).

[0256] - Measurement of Control Solution - The control solution was measured in the same manner as the test sample solution, except that 100 μL of the test sample solution was replaced with 100 μL of FBS-free High-DMEM.

[0257] - Calculation of 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 was calculated using the following formula (12): Type I collagen production promotion rate (%) = A / B × 100 Formula (12) In formula (12), "A" and "B" are as follows: A: amount of type I collagen in the test sample solution (when the test sample was added) B: amount of type I collagen in the control solution (when the test sample was not added)

[0258] <Results> The rate of promotion of type I collagen production is shown in Table 15. As shown in Table 15, norathyriol was found to have a significant effect of promoting type I collagen production.

[0259]

[0260] (Test Example 13: DPPIV activity inhibitory effect test) <Test method> - Preparation of test sample solution - As mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in 25 mmol / L Tris-HCl buffer solution (pH 8.0) was used. As norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in 25 mmol / L Tris-HCl buffer solution (pH 8.0) was used.

[0261] Measurement of Test Sample Solution 25 μL of the test sample solution and 25 μL of a 0.4 μg / mL DPPIV (rhCD26) solution (manufactured by R&D Systems) were added to a 96-well plate, 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 a 0.5 mmol / L Gly-Pro-p-NA.Tos[GPNT] solution (manufactured by Peptide Institute, Inc.) prepared in 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the mixture was allowed to react at 37°C for 90 minutes. After completion of the reaction, the absorbance at a wavelength of 415 nm was measured.

[0262] - Measurement of test sample solution blank - 25 μL of the test sample solution and 25 μL of 25 mmol / L Tris-HCl buffer (pH 8.0) were added to a 96-well plate without adding 0.4 μg / mL DPPIV (rhCD26) solution, and the mixture was 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 a 0.5 mmol / L Gly-Pro-p-NA.Tos[GPNT] solution prepared in 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the mixture was allowed to react at 37°C for 90 minutes. After completion of the reaction, the absorbance at a wavelength of 415 nm was measured.

[0263] - Measurement of control solution - To a 96-well plate, 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 without adding the test sample solution, mixed, 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 in 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the mixture was allowed to react at 37°C for 90 minutes. After completion of the reaction, the absorbance at a wavelength of 415 nm was measured.

[0264] - Measurement of control solution blank - 50 μL of 25 mmol / L Tris-HCl buffer (pH 8.0) was preincubated at 37°C for 5 minutes in a 96-well plate without adding the test sample solution or 0.4 μg / mL DPPIV (rhCD26) solution. Then, 50 μL of 0.5 mmol / L Gly-Pro-p-NA.Tos[GPNT] solution prepared in 25 mmol / L Tris-HCl buffer (pH 8.0) was added, and the mixture was allowed to react at 37°C for 90 minutes. After completion of the reaction, the absorbance at a wavelength of 415 nm was measured.

[0265] - Calculation of DPPIV activity inhibition rate - Based on the absorbances obtained by measuring the test sample solution, the control solution, and the control solution blank, the DPPIV activity inhibition rate was calculated using the following formula (13): DPPIV activity inhibition rate (%) = {1 - (A - B) / (C - D)} x 100 ... formula (13) In 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 test sample solution blank (test sample added, no enzyme added) at a wavelength of 415 nm C: absorbance of the control solution (test sample not added, enzyme added) at a wavelength of 415 nm D: absorbance of the control solution blank (test sample not added, no enzyme added) at a wavelength of 415 nm

[0266] <Results> The DPPIV activity inhibition rate is shown in the following Table 16. As shown in the following Table 16, both mangiferin and norathyriol were found to have a weak inhibitory effect on DPPIV activity.

[0267]

[0268] (Test Example 14: Myoblast proliferation promoting activity test) <Test method> - Preparation of test sample solution - For mangiferin as a test sample, a solution prepared by dissolving M3547 (lot number: SLBQ6689V, manufactured by SIGMA) in DMEM containing 5% by volume of FBS was used. For norathyriol as a test sample, a solution prepared by dissolving ALB-RS-1643 (lot number: ALB-202105, manufactured by SIGMA) in DMEM containing 5% by volume of FBS was used.

[0269] - Pre-culture of mouse skeletal muscle-derived myoblasts - Mouse skeletal muscle-derived myoblasts (C2C12) (obtained from DS Pharma Biomedical) were cultured in DMEM containing 10% by volume of FBS, and then collected using a cell scraper. The collected cells were collected at a concentration of 2.0 × 10 ４ The cells were diluted with DMEM containing 5% by volume of FBS to a concentration of 100 cells / mL, and then seeded in a collagen-coated 96-well plate (manufactured by IWAKI) at 100 μL per well. The culture medium was then incubated at 37°C and 5% CO ２ The mixture was incubated under reduced pressure for 6 hours.

[0270] - Measurement of test sample solution - 100 μL of test sample solution was added to each well of pre-cultured mouse skeletal muscle-derived myoblast cells (C2C12) to give the final concentration shown in Table 17 below, and the cells were incubated at 37°C and 5% CO ２ The cells were cultured for 2 days under a constant temperature of 37°C and 5% CO. The myoblast proliferation-promoting activity was measured using the MTT assay. After the culture was completed, the medium was removed, and 100 μL of MTT (Dojindo Laboratories) dissolved in PBS(-) at a final concentration of 0.4 mg / mL was added to each well. ２ After culturing for 2 hours under 2-propanol, the blue formazan produced in the cells was extracted with 100 μL of 2-propanol. After extraction, the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two (absorbance at a wavelength of 570 nm - absorbance at a wavelength of 650 nm) was taken as the amount of blue formazan produced. - Measurement of Control Solution - The control solution was measured in the same manner as the test sample solution, except that 100 μL of test sample solution was replaced with 100 μL of DMEM containing 5% by volume of FBS.

[0271] - Calculation of myoblast proliferation promotion rate - Based on the amount of blue formazan produced obtained by measuring the test sample solution and the control solution, the myoblast proliferation promotion rate was calculated using the following formula (14): Astrocyte proliferation promotion rate (%) = A / B × 100 ... formula (14) In formula (14), "A" and "B" are as follows: A: Amount of blue formazan produced in cells in the test sample solution (when the test sample was added) B: Amount of blue formazan produced in cells in the control solution (when the test sample was not added)

[0272] <Results> The myoblast proliferation promotion rate is shown in the following Table 17. As shown in the following Table 17, a significant myoblast proliferation promotion effect was observed for mangiferin and norathyriol at low concentrations.

[0273]

[0274] The present invention provides, for example, the following aspects: [1] An anti-obesity agent characterized by containing, as an active ingredient, a compound represented by the following general formula (1): However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond. [2] The anti-obesity agent according to the above item [1], which has one or more effects selected from the group consisting of an α-glucosidase activity inhibitory effect and a lipase activity inhibitory effect. [3] An anti-inflammatory agent characterized by containing a compound represented by the following general formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond. [4] The anti-inflammatory agent according to the above [3], which has one or more effects selected from the group consisting of an inhibitory effect on hexosaminidase release and an inhibitory effect on prostaglandin E2 production. [5] A brain function improver, characterized by containing a compound represented by the following general formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond. [6] The brain function improver according to the above item [5], which has one or more effects selected from the group consisting of promoting astrocyte cell proliferation, promoting aquaporin 4 mRNA expression in astrocytes, suppressing tumor necrosis factor (TNF-α) production in microglia, suppressing the expression of genes related to inflammation-inducing factors in microglia, and increasing the expression of genes related to inflammation-inducing factors in microglia. [7] A liver function improver, characterized by containing a compound represented by the following general formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond. [8] The liver function improver according to the above [7], which has one or more actions 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 by containing a compound represented by the following general formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond.

[10] The bone strengthening agent according to the above item [9], which has an effect of promoting type I collagen production.

[11] A blood sugar level improving agent, characterized by containing a compound represented by the following general formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). In the general formula (2), * represents a bond.

[12] The blood glucose level improving agent according to the above item

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

[13] A muscle strengthening agent characterized by containing a compound represented by the following general formula (1) as an active ingredient: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). wherein * represents a bond in the general formula (2).

[14] The muscle-strengthening agent according to

[13] , which has a myoblast proliferation-promoting effect.

[15] An oral composition comprising at least one selected from the group consisting of the anti-obesity agent according to any one of [1] to [2], the anti-inflammatory agent according to any one of [3] to [4], the brain function improver according to any one of [5] to [6], the liver function improver according to any one of [7] to [8], the bone strengthening agent according to any one of [9] to

[10] , the blood glucose level improving agent according to any one of

[11] to

[12] , and the muscle-strengthening agent according to any one of

[13] to

[14] .

[16] A cosmetic composition comprising at least one selected from the group consisting of the anti-obesity agent according to any one of [1] to [2], the anti-inflammatory agent according to any one of [3] to [4], the brain function improver according to any one of [5] to [6], the liver function improver according to any one of [7] to [8], the bone strengthener according to any one of [9] to

[10] , the blood sugar level improving agent according to any one of

[11] to

[12] , and the muscle strengthener according to any one of

[13] to

[14] .

[0275]

[17] A compound represented by the following general formula (1) for use in anti-obesity, anti-inflammatory, brain function improvement, liver function improvement, bone strengthening, blood sugar level improvement, or muscle strengthening: However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). wherein * represents a bond in the general formula (2).

[18] The compound according to

[17] , wherein the anti-obesity use is one or more uses selected from the group consisting of inhibiting α-glucosidase activity and inhibiting lipase activity.

[19] The compound according to

[17] , wherein the anti-inflammatory use is one or more uses selected from the group consisting of inhibiting hexosaminidase release and inhibiting prostaglandin E2 production.

[20] The compound according to

[17] , wherein the brain function improvement use is one or more uses selected from the group consisting of promoting astrocyte proliferation, promoting astrocyte aquaporin 4 mRNA expression, suppressing microglial tumor necrosis factor (TNF-α) production, suppressing microglial expression of inflammation-inducing factor-related genes, and increasing microglial expression of inflammation-inhibiting factor-related genes.

[21] The compound according to

[17] , wherein the use for improving liver function is one or more selected from the group consisting of promoting glutathione production in hepatocytes, promoting ATP production in hepatocytes, and promoting hepatocyte proliferation.

[22] The compound according to

[17] , wherein the use for strengthening bones is promoting type I collagen production.

[23] The compound according to

[17] , wherein the use for improving blood sugar levels is inhibiting dipeptidyl peptidase IV activity.

[24] The compound according to

[17] , wherein the use for strengthening muscles is promoting myoblast proliferation.

[25] Use of the compound according to any one of

[17] to

[24] , which is for oral administration.

[26] Use of the compound according to any one of

[17] to

[24] , which is for cosmetics.

[0276]

[27] Use of a compound represented by the following general formula (1) in the manufacture of a pharmaceutical agent for anti-obesity, anti-inflammatory, brain function improvement, liver function improvement, bone strengthening, blood sugar level improvement, or muscle strengthening: However, in the general formula (1), R １represents H or a group represented by the following general formula (2). wherein * represents a bond in the general formula (2).

[28] Use of the compound according to

[27] above, wherein the anti-obesity pharmaceutical agent has one or more effects selected from the group consisting of an α-glucosidase activity inhibitory effect and a lipase activity inhibitory effect.

[29] Use of the compound according to

[17] above, wherein the anti-inflammatory pharmaceutical agent has one or more effects selected from the group consisting of a hexosaminidase release inhibitory effect and a prostaglandin E2 production inhibitory effect.

[30] Use of the compound according to

[17] above, wherein the brain function improving pharmaceutical agent has one or more effects selected from the group consisting of an aquaporin 4 mRNA expression promoting effect in astrocytes, an inhibitory effect on tumor necrosis factor (TNF-α) production in microglia, an inhibitory effect on the expression of inflammation-inducing factor-related genes in microglia, and an increase in the expression of inflammation-inhibiting factor-related genes in microglia.

[31] Use of the compound according to

[17] above, wherein the pharmaceutical 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.

[32] Use of the compound according to

[17] above, wherein the pharmaceutical for strengthening bones has a type I collagen production promoting effect.

[33] Use of the compound according to

[17] above, wherein the pharmaceutical for improving blood sugar levels has a dipeptidyl peptidase IV activity inhibitory effect.

[34] Use of the compound according to

[17] above, wherein the pharmaceutical for strengthening muscles has a myoblast proliferation promoting effect.

[35] Use of the compound according to any one of

[27] to

[34] above, wherein the compound is used for oral administration.

[36] Use of the compound according to any one of

[27] to

[34] above, wherein the compound is used for cosmetics.

[0277] This international application claims priority based on Japanese Patent Application No. 2023-221743, filed on December 27, 2023, the entire contents of which are incorporated herein by reference.

Claims

1. An anti-obesity agent characterized by containing, as an active ingredient, a compound represented by the following general formula (1). However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond.

2. The anti-obesity agent according to claim 1, having at least one action selected from the group consisting of an α-glucosidase activity inhibitory action and a lipase activity inhibitory action.

3. An anti-inflammatory agent characterized by containing, as an active ingredient, a compound represented by the following general formula (1). However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond.

4. The anti-inflammatory agent according to claim 3, having at least one action selected from the group consisting of a hexosaminidase release inhibitory action and a prostaglandin E2 production inhibitory action.

5. A cerebrofunction-improving agent characterized by containing, as an active ingredient, a compound represented by the following general formula (1). However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond.

6. The brain function improving agent according to claim 5, having at least one action selected from the group consisting of an astrocyte cell growth promoting action, an aquaporin 4 mRNA expression promoting action in astrocytes, a tumor necrosis factor (TNF-α) production inhibitory action in microglia, an inflammatory inducer-related gene expression inhibitory action in microglia, and an inflammatory inhibitor-related gene expression enhancing action in microglia.

7. A liver function improver characterized by containing, as an active ingredient, a compound represented by the following general formula (1). However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond.

8. The liver function improving agent according to claim 7, having at least one action selected from the group consisting of a glutathione production promoting action in hepatocytes, an ATP production promoting action in hepatocytes, and a hepatocyte growth promoting action.

9. An osteogenic agent characterized by containing, as an active ingredient, a compound represented by the following general formula (1). However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond.

10. The bone strengthening agent according to claim 9, having a type I collagen production promoting action.

11. A blood glucose level improving agent characterized by containing, as an active ingredient, a compound represented by the following general formula (1). However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond.

12. The blood glucose level improving agent according to claim 11, having a dipeptidyl peptidase IV activity inhibitory action.

13. A muscle strengthening agent characterized by containing, as an active ingredient, a compound represented by the following general formula (1). However, in the general formula (1), R １ represents H or a group represented by the following general formula (2). However, in the general formula (2), * represents a bond.

14. The muscle strengthening agent according to claim 13, having a myoblast growth promoting action.

15. An oral composition, characterized by containing at least any one selected from the group consisting of the anti-obesity agent according to claim 1, the anti-inflammatory agent according to claim 3, the brain function improving agent according to claim 5, the liver function improving agent according to claim 7, the bone strengthening agent according to claim 9, the blood glucose level improving agent according to claim 11, and the muscle strengthening agent according to claim 13.

16. A cosmetic composition, characterized by containing at least any one selected from the group consisting of the anti-obesity agent according to claim 1, the anti-inflammatory agent according to claim 3, the brain function improving agent according to claim 5, the liver function improving agent according to claim 7, the bone strengthening agent according to claim 9, the blood glucose level improving agent according to claim 11, and the muscle strengthening agent according to claim 13.

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