WO2010089874A1 - Ppar-γ-expression-enhancing agent, adiponectin-production-enhancing agent, ucp-activating agent, and pharmaceutical preparation, food or beverage comprising any one of the agents - Google Patents

Abstract

Disclosed are: a PPAR-γ-expression-enhancing agent which comprises procyanidin B2 as an active ingredient and has an activity of enhancing the expression of PPAR-γ; an adiponectin-production-promoting agent which comprises procyanidin B2 as an active ingredient and has an activity of promoting the production of adiponectin; an UCP-activating agent which comprises procyanidin B2 as an active ingredient and has an activity of enhancing the expression of UCP; an anti-diabetes agent, an anti-obesity agent, an agent for reducing the accumulation of a visceral fat or an agent for inhibiting the accumulation of a visceral fat, which comprises any one of the PPAR-γ-expression-enhancing agent, the adiponectin-production-promoting agent and the UCP-activating agent; and a food or beverage comprising any one of the PPAR-γ-expression-enhancing agent, the adiponectin-production-promoting agent and the UCP-activating agent. It becomes possible to provide a pharmaceutical preparation, a food or a beverage which does not cause any adverse side effect, is harmless for a human body, and is expected to have an effect of enhancing the expression of PPAR-γ, an effect of promoting the production of adiponectin, an effect of enhancing the expression of UCP, an effect of ameliorating obesity, diabetes or the like which is induced by the effect of enhancing the expression of PPAR-γ, the effect of promoting the production of adiponectin or the effect of enhancing the expression of UCP, or the like.

Description

PPAR-γ expression enhancer, adiponectin production promoter, UCP activator, and pharmaceuticals and foods using them

The present invention relates to a PPAR-γ [peroxisome proliferators-activated receptor γ] expression enhancer, adiponectin production promoter, UCP [uncoupling protein] activator and use thereof This is related to pharmaceuticals and foods.

Prevention and treatment of obesity is a very important issue in maintaining and improving health. Obesity causes type 2 diabetes, hypertension, hyperlipidemia and the like. Furthermore, these diseases are also basic diseases such as stroke and ischemic heart disease. Currently, these diseases are understood as a series of metabolic abnormalities based on insulin resistance caused by obesity. Recent molecular biological studies have revealed the existence of various factors involved in obesity and insulin resistance.

One of the factors attracting attention as the above factor is adiponectin. Adiponectin (Acrp30, AdipoQ, GBP28) is an adipocytokine that improves insulin resistance. Adiponectin is identified as a gene that is most abundantly expressed in human adipose tissue (Non-patent Document 1). In obesity, diabetes, and ischemic heart disease, adiponectin concentration in blood is decreased, and it has been confirmed that adiponectin has an anti-diabetic action and an anti-arteriosclerosis action (Non-Patent Documents 2 to 6). Hypoadiponectinemia due to obesity and fat accumulation is considered to lead to insulin resistance syndrome such as diabetes and hyperlipidemia, systemic metabolic syndrome, arteriosclerosis and the like (Non-patent Document 7).

Along with adiponectin, PPAR (peroxisome-proliferators-activated receptor) is also a factor involved in obesity and insulin resistance. PPAR is a transcription factor belonging to the nuclear receptor superfamily, and has α, γ, and δ subtypes in mammals. PPAR forms a heterodimer with a retinoid X receptor (RXR) and induces expression of a target gene having a PPAR response element (PPRE) in its promoter region in a ligand-dependent manner.

Of these subtypes, PPAR-γ is known to control adipocyte differentiation and hypertrophy. Studies using PPAR-γ hetero-deficient mice have revealed that PPAR-γ mediates obesity and insulin resistance. Suppressing hypertrophic adipogenesis by suppressing the intrinsic activity of PPAR-γ is considered to be useful as an anti-obesity / anti-diabetic treatment (Non-patent Document 7).

Thus, since PPAR and adiponectin act as insulin resistance improving substances, it is considered effective for the prevention and treatment of obesity and diabetes. Appropriate dietary management is fundamental in the prevention and treatment of diabetes. Therefore, if a food that can activate and enhance production of PPAR and adiponectin is developed, it can be an effective means for preventing and treating diabetes. Furthermore, it can be expected to be effective against other diseases based on insulin resistance.

In recent years, research on uncoupling protein (UCP), which is a membrane protein present in the inner mitochondrial membrane, is also underway. UCP is considered to generate heat by eliminating the proton concentration gradient in the inner membrane caused by respiration without synthesizing ATP. And since UCP can heat the energy stored as fat in the cells without going through other energy consumption processes, it is considered that UCP plays an important role in maintaining the body temperature of a thermostat animal. Moreover, since it has such a function, it is considered that it is one of the important factors which determine the energy metabolic efficiency of a thermostat animal. Currently, three types of UCP have been identified and are called UCP-1, UCP-2, and UCP-3. In particular, UCP-2 is expressed in a wide variety of tissues, and by activating UCP-2, energy consumption can be increased without exercising, so it is an effective means of preventing and treating obesity. sell. UCP-2 is also thought to be involved in the response to infectious diseases such as diabetes and colds.

From the above, in the prevention and treatment of obesity, diabetes and the like, enhanced expression of PPAR-γ, promotion of adiponectin production, and activation of UCP can be effective means. In recent years, various types of drugs having such functions have been researched and developed. However, many conventional drugs have strong side effects, and therefore, few drugs are preferably included in daily foods and drinks. Is the actual situation. Under such circumstances, adiponectin secretion containing, as an active ingredient, green tea catechin (epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, catechin gallate, epigallocatechin, gallocatechin, epicatechin, (+)-catechin) developed recently. The composition for promoting the secretion of adiponectin and the composition for promoting adiponectin containing proanthocyanidins contained in the grape extract as an active ingredient are derived from plants conventionally used as food, and are used for daily foods and drinks. It can be said that the safety is high in application (see Patent Documents 1 to 3).
JP 2006-131512 A JP 2006-182706 A WO2004 / 78741 Maeda K, Okubo K, Shimomura I, et al: cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (Adipose Most Abundant Gene transcript 1). Biochem Biophys Res Communi 1996; 221: 286-289 Hotta K, Funahashi T, Arita Y, et al: Plasma concentrations of anovel, adipose-specific protein, adiponectin, in type 2 diabetic patients.Arterioscler Thromb Vasc Biol 2000; 20: 1595-1599. Ouchi N, Kihara S, Arita Y, et al: Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulati on 1999; 100: 2473-2476. Kondo H, Shimomura I, Matsukawa Y, et al: Association of adiponectin / ACRP 30 / AdipoQ mutation with type 2 diabetes mellitus. A candidate gene for the insulin resistance syndrome. Diabetes 2002; 51: 2325-2328. Maeda N, Shimomura I, Kishida K, et al: Diet-induced insulin resistance in mice lacking adiponectin / ACRP 30.Nature Medicine 2002; 8: 731-737. Matsuda M, Shimomura I, Sata M, et al: Role of adiponectin n preventing vascular stenosis ― the missing link of adipo-vascular axis―. J Biol Chem 2002; 277: 37487-37491. Takashi Kadowaki, Molecular Mechanism of Insulin Resistance by Adipocytes, Proceedings of the 124th Symposium of the Japanese Society of Medical Sciences, "Science of Obesity", p110-121 (2003)

However, the adiponectin secretion-promoting compositions disclosed in Patent Documents 1 to 3 are actually not so high in adiponectin secretion-promoting performance and are compared with the performance of troglitazone (thiazolidinedione-based antidiabetic agent), which is a chemical. And quite inferior. Therefore, further improvement of the performance is expected by further research. Similarly, in the fields of PPAR-γ expression enhancer and UCP activator, development of a drug excellent in PPAR-γ expression enhancement and UCP activity ability is expected with no side effects even if it is included in daily foods and drinks. Has been.

The present invention has been made in view of such circumstances, and is gentle to the human body without causing side effects, and can provide a PPAR-γ expression enhancing effect, an adiponectin production promoting effect, a UCP expression enhancing effect, The purpose is to provide pharmaceuticals and foods and drinks that can be expected to improve obesity, diabetes, etc. due to their effects.

In order to achieve the above object, the first gist of the present invention is a PPAR-γ expression enhancer containing procyanidin B2 as an active ingredient and having a PPAR-γ expression enhancing action.

The second gist of the present invention is an adiponectin production promoter containing procyanidin B2 as an active ingredient and having an adiponectin production promoting action.

The third gist of the present invention is a UCP activator containing procyanidin B2 as an active ingredient and having a UCP expression enhancing action.

The fourth aspect of the present invention is an anti-diabetic agent, an anti-obesity agent, a visceral fat accumulation reducing agent, or a visceral fat accumulation inhibitor comprising the drugs of the first to third aspects.

The fifth aspect of the present invention is a food / beverage product containing the drugs of the first to fourth aspects.

That is, the present inventors have conducted intensive research to solve the above problems. In the course of the research, we focused on procyanidins, for which various physiological effects have been reported. Procyanidins are polymers of epicatechin, and there are polymers such as dimers, trimers, tetramers, pentamers, etc. Isomers also exist. These have different physiological effects. The inventors further advanced research on such procyanidins. As a result, when procyanidin B2 which is a kind of procyanidin dimer is used as an active ingredient in the effect of enhancing the expression of PPAR-γ, the effect of promoting the production of adiponectin, and the effect of enhancing the expression of UCP, it is extremely effective compared to other procyanidins. It was newly confirmed by experiment that this is recognized. In addition, when these effects are exerted, in particular, an improvement effect such as obesity / diabetes can be obtained, and therefore anti-diabetic agents, anti-obesity agents, visceral accumulated fat reducing agents, visceral fat accumulation inhibiting agents It was found that it can also be applied to the use of pharmaceuticals such as Furthermore, since procyanidin B2 does not cause side effects, it is highly safe and can be suitable for inclusion in daily foods and drinks, and it has been found that the intended purpose can be achieved. Reached.

As described above, the PPAR-γ expression enhancer of the present invention contains procyanidin B2 as an active ingredient and has a PPAR-γ expression enhancing action. Moreover, the adiponectin production promoter of this invention contains procyanidin B2 as an active ingredient, and has an adiponectin production promotion effect. The UCP activator of the present invention contains procyanidin B2 as an active ingredient and has a UCP expression enhancing action. These drugs are considered to be free of substances that inhibit their action, etc., so that their actions can be demonstrated effectively in their respective applications. The content ratio of procyanidin B2, which is an active ingredient, is defined so as to be able to do so. As a result, each of the above-mentioned drugs is gentle to the human body without causing side effects, and has an effect of enhancing PPAR-γ expression, an effect of promoting adiponectin production, an effect of enhancing UCP expression, and various diseases related to the prevention and improvement Can be demonstrated.

In particular, when the above-described effects can be exhibited well, excellent effects such as obesity and diabetes can be exhibited. Therefore, the above drugs can be advantageously applied to pharmaceutical uses such as antidiabetic agents, antiobesity agents, visceral fat accumulation reducing agents, visceral fat accumulation inhibitors.

When a food or drink containing the above-mentioned drug containing procyanidin B2 as an active ingredient is continuously consumed in the same manner as a normal food or drink, the adiponectin production promoting effect, UCP expression enhancing effect, PPAR- The effect of enhancing the expression of γ and the accompanying improvement effect such as obesity and diabetes can be obtained.

FIG. 3 is a graph showing differences in the gene expression level of PPAR-γ caused by pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8). FIG. 3 is a graph showing the difference in the gene expression level of adiponectin caused by pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8). FIG. 3 is a graph showing the difference in UCP-2 gene expression level resulting from pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8). FIG. 3 is a graph showing the difference in the gene expression level of PPAR-γ caused by pretreatment of 3T3-L1 cells (pretreatment with samples a to g). FIG. 3 is a graph showing the difference in the gene expression level of adiponectin caused by pretreatment of 3T3-L1 cells (pretreatment with samples a to g). FIG. 6 is a graph showing the difference in UCP-2 gene expression level resulting from pretreatment of 3T3-L1 cells (pretreatment with samples a to g).

Next, an embodiment of the present invention will be described in detail.

As described above, the PPAR-γ expression enhancer of the present invention contains procyanidin B2 as an active ingredient and has a PPAR-γ expression enhancing action. Moreover, the adiponectin production promoter of this invention contains procyanidin B2 as an active ingredient, and has an adiponectin production promotion effect. The UCP activator of the present invention contains procyanidin B2 as an active ingredient and has a UCP expression enhancing action (particularly a UCP-2 expression enhancing action). These drugs are considered to be free of substances that inhibit their action, etc., so that their actions can be demonstrated effectively in their respective applications. The content ratio of procyanidin B2, which is an active ingredient, is defined so as to be able to do so. The chemical structure (steric structure) of procyanidin B2 is as shown in the following chemical formula (1).

And even if said procyanidin B2 is what was refine | purified and extracted from the composition which the living organisms which exist in nature hold or produce, by carrying out the chemical synthesis | combination by promoting the polymerization of epicatechin, etc. It may be prepared and obtained by a biological method using a microorganism or the like.

Procyanidin B2 is abundant in plants such as black soybean seed coat, apple, cacao, grape, cinnamon, mutamba, hawthorn, bunoki, carambola, mother wort, keclopia, cola (cola nut) and the like. As a method for extracting procyanidin B2 from these plants, for example, the above plant is immersed in an extraction solvent. As an extraction solvent for procyanidin B2, for example, water, or a water-soluble solvent such as methanol, ethanol, isopropanol, n-propanol, and acetone is used. Particularly, when black soybean seed coat is used as a raw material, Since procyanidins of about 1 to 30 mer are contained, procyanidins with a high degree of polymerization are mixed when extracted with lower alcohol or acetone. Therefore, in this case, a 0.01 to 10% by weight sulfuric acid aqueous solution is preferably used as one capable of extracting procyanidin B2 with high purity. Moreover, it is preferable from the point of purity and stability that the extraction temperature by the said extraction solvent is 70 degrees C or less.

A fraction containing procyanidin B2 at a high purity is extracted from the extract thus obtained by adsorption treatment, resin purification treatment, gel filtration treatment, ion exchange treatment, membrane separation treatment, salt precipitation treatment, and the like. Then, by drying and concentrating it, the target procyanidin B2 can be obtained.

The PPAR-γ expression enhancer of the present invention preferably has a procyanidin B2 content in the range of 0.01 to 100% by weight, more preferably from the viewpoint of the effectiveness of its PPAR-γ expression enhancing action. It is in the range of 10 to 100% by weight. In addition, the adiponectin production promoter of the present invention preferably has a procyanidin B2 content in the range of 0.01 to 100% by weight, more preferably 10 to 10% from the viewpoint of the effectiveness of the adiponectin production promoting action. It is in the range of 100% by weight. The UCP activator of the present invention preferably has a procyanidin B2 content in the range of 0.01 to 100% by weight, more preferably 10 to 100, from the viewpoint of the effectiveness of its UCP expression enhancing action. It is in the range of wt%.

Furthermore, the amount of the PPAR-γ expression enhancer of the present invention is preferably set so that the daily procyanidin B2 intake is in the range of 0.1 to 1000 mg, more preferably from the viewpoint of effectiveness. Is in the range of 5 to 500 mg. From the viewpoint of effectiveness, the adiponectin production promoter of the present invention is preferably set in an amount such that the daily procyanidin B2 intake is in the range of 0.1 to 1000 mg, more preferably 5 to 500 mg. Range. From the viewpoint of effectiveness, the UCP activator of the present invention is preferably set so that the daily procyanidin B2 intake is in the range of 0.1 to 1000 mg, more preferably 5 to 500 mg. It is a range.

In addition, since it can exert an excellent effect in preventing and improving obesity / diabetes, etc. by exerting each of the above effects well, an antidiabetic agent, an antiobesity agent, a visceral accumulated fat reducing agent, When applied to the use of a pharmaceutical such as a visceral fat accumulation inhibitor, the procyanidin B2 content and the daily procyanidin B2 intake are in accordance with the ratios defined for the respective drugs.

Further, in the above respective drugs of the present invention, the above procyanidin B2 extract may be used directly, but generally, the above extract is dissolved or dispersed in a suitable liquid carrier, What was mixed with the powder carrier is used.

Examples of pharmacologically acceptable carriers include excipients, lubricants, binders and disintegrants in solid preparations, or solvents, solubilizers, suspending agents, and isotonic agents in liquid preparations. , Buffering agents and soothing agents.

In addition, in the preparation of the drug of the present invention, various components usually used for the preparation are arbitrarily used in the preparation. Examples thereof include starch, dextrin, lactose, corn starch, inorganic salts, and the like. Can be given.

Examples of the dosage form of the drug of the present invention include ampoules, tablets, capsules, granules, fine granules, powders, infusions, drinks and the like.

Furthermore, the drug of the present invention can be provided as a form in which it is associated with food and drink. Examples of the foods and drinks include health foods (tablets, powders, granules, concentrated liquids), soft drinks, foods for specified health use, drinks, tea, milk, pudding, jelly, rice cake, gum, yogurt, chocolate, soup, cookies , Snacks, wine, shochu, sake, dressing, boiled beans, tofu, natto, soy milk, roasted beans, dried beans, miso, etc. And the obesity suppression effect comes to be obtained by eating and drinking these food and drink similarly to normal food and drink.

The drug of the present invention is friendly to the human body without causing side effects, and has a PPAR-γ expression enhancing effect, an adiponectin production promoting effect, a UCP expression enhancing effect (particularly a UCP-2 expression enhancing effect), and various diseases related thereto (In particular, obesity and diabetes) can be prevented and improved. Moreover, the above-mentioned effects can be obtained not only in humans but also in animals such as pets and livestock, and the dose is determined based on conditions such as differences in organisms to be administered, sex, weight, age, etc. It is set appropriately according to And as above-mentioned, since the chemical | medical agent of this invention can obtain the obesity suppression effect etc. also in animals, such as a pet and livestock, it can also provide as a form related to pet food and feed. .

Next, examples will be described. However, the present invention is not limited to these examples.

<Experiment method>
Mouse-derived preadipocytes 3T3-L1 were cultured in a DME medium (Dulbecco's modified Eagle medium; hereinafter referred to as “basic medium”) containing 10% by volume of fetal bovine serum using a 24-well plate at 37 ° C., 5 The culture was performed in a volume% CO ₂ atmosphere environment. Then, after this culture, 3T3-L1 cells reached 100% confluence, and then, in the basic medium, three types of reagents, dexamethasone, methylisobutylxanthine, and insulin, respectively, dexamethasone 1 μmol / l, and methylisobutylxanthine 0.1%. Differentiation induction treatment was performed by adding 25 μmol / l insulin to a concentration of 2 μmol / l, and the 3T3-L1 cells were differentiated into adipocytes. The differentiation induction treatment is continued for 3 days, and then the 3T3-L1 cells are cultured for about 1 week by adding only insulin to the basic medium (insulin concentration: 2 μmol / l) to mature the adipocytes. It was. Thus, by adding any one of samples 1 to 8 shown in Table 1 below at a rate of 1% by volume to 3T3-L1 cells differentiated into mature adipocytes and culturing for 12 hours, Was pretreated. In addition, the pre-processing by the difference of the said sample was performed on the same conditions under the same environment. After the pretreatment, the medium is removed, the cells are washed with a phosphate buffer, and then the cells are washed with a basic medium supplemented with 10 ng / ml of inflammation-inducing cytokine TNF-α. Was again cultured for 12 hours (stress treatment).

The sample 4 shown in Table 1 is procyanidin B2, which is a kind of procyanidin dimer, and its chemical structure (steric structure) is as shown in the following chemical formula (1).

Sample 5 shown in Table 1 is procyanidin C1, which is a kind of procyanidin trimer, and its chemical structure (stereostructure) is as shown in the following chemical formula (2).

After the stress treatment, the medium was removed, and then RNA was extracted from the 3T3-L1 cells using an RNA extraction reagent (QIAzol, manufactured by Qiagen) (use according to the reagent instruction manual). Furthermore, cDNA was synthesized by reverse transcription reaction using the extracted total RNA as a template by Super Script III first strand synthesis system (manufactured by Invitrogen). The cDNA thus obtained was analyzed, and the difference in the expression levels of PPAR-γ, adiponectin, and UCP-2 in 3T3-L1 cells caused by the pretreatment of 3T3-L1 cells with samples 1 to 8 was verified. The extent to which the pretreatment reduces the stress due to TNF-α was confirmed by the expression behavior of the gene. Specifically, this verification was performed by quantifying the expression level (Relative mRNA Levels) of each gene of PPAR-γ, adiponectin, and UCP-2 in the above cDNA by real-time PCR using a light cycler (Roche). . In addition, the primer sequences of each gene are as shown in Table 2 below. In addition, SYBR Premix Ex Taq (manufactured by Takara Bio Inc.) is used as a reaction solution for this determination, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is used as a gene for data correction (normalization). It was.

The difference in the gene expression level of PPAR-γ due to the pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8) by the above quantification is as shown in Table 3 below. FIG. 1 is a graph showing the results.

From the above Table 3 and FIG. 1, it was confirmed that the sample 4 (procyanidin B2) as an example product exhibited the highest PPAR-γ expression enhancing action in the PPAR-γ expression enhancing application. In particular, the PPAR-γ gene expression level of sample 4 was significantly different from the PPAR-γ gene expression levels of all other samples at a risk rate of less than 5%.

In addition, the difference in the gene expression level of adiponectin caused by the pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8) by the above quantification is as shown in Table 4 below. FIG. 2 is a graph showing the results.

From the above Table 4 and FIG. 2, in the adiponectin production promotion application, sample 4 (procyanidin B2) as an example product has a high adiponectin production promotion effect next to troglitazone (sample 8), which is a conventional diabetes therapeutic chemical. It was accepted to show. In particular, the adiponectin gene expression level by the use of sample 4 was significantly different from the adiponectin gene expression level of all other samples except sample 8 at a risk rate of less than 5%.

In addition, the difference in UCP-2 gene expression level due to the above-described quantitative pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8) is as shown in Table 5 below. FIG. 3 is a graph showing the results.

From Table 5 and FIG. 3, it was confirmed that in the UCP-2 expression application, sample 4 (procyanidin B2) as an example product showed the highest UCP-2 expression enhancing action. In particular, the gene expression level of UCP-2 due to the use of sample 4 is significantly different from the UCP-2 gene expression level of sample 1, sample 3, sample 5, sample 6, and sample 7 at a risk rate of less than 5%. Admitted.

From the results of Example 1 above, among the samples used for pretreatment of 3T3-L1 cells differentiated into mature adipocytes, procyanidin B2 (sample 4) has a high PPAR-γ expression enhancing action and adiponectin production promoting action. Since the UCP-2 expression enhancing action was observed, in Example 2, a comparative experiment was conducted with the case where a compound (sample) closer to procyanidin B2 was used in terms of chemical structure, physical properties, and the like.

That is, any of samples a to g shown in Table 6 below was used as a sample used for pretreatment of 3T3-L1 cells differentiated into mature adipocytes. In addition, the pre-processing by the difference of the said sample was performed on the same conditions under the same environment. Otherwise, the experiment was carried out in the same manner as in the experimental method of Example 1, RNA extraction after stress treatment with TNF-α following the above pretreatment and its reverse transcription reaction, and further, each gene expression level (PPAR) by real-time PCR Quantification of -γ, adiponectin and UCP-2 gene expression levels) was also performed in the same manner as in Example 1.

Sample c shown in Table 6 above is procyanidin B1, which is a kind of procyanidin dimer, and its chemical structure (stereostructure) is as shown in the following chemical formula (3).

The difference in the gene expression level of PPAR-γ due to the pretreatment of 3T3-L1 cells (pretreatment with samples a to g) by the above quantification is as shown in Table 7 below. FIG. 4 is a graph showing the results.

From Table 7 and FIG. 4, it was confirmed that the sample b (procyanidin B2) as an example product exhibited the highest PPAR-γ expression enhancing action in the PPAR-γ expression enhancing use. In particular, the PPAR-γ gene expression level in sample b was significantly different from the PPAR-γ gene expression level in all other samples except sample f at a risk rate of less than 5%.

In addition, the difference in the gene expression level of adiponectin caused by the pretreatment of 3T3-L1 cells (pretreatment with samples a to g) by the above quantification is as shown in Table 8 below. FIG. 5 is a graph showing the results.

From Table 8 and FIG. 5, in the adiponectin production promotion application, the sample b (procyanidin B2) as an example product has a high adiponectin production promotion effect next to troglitazone (sample g), which is a conventional chemical for treating diabetes. It was accepted to show. In particular, the adiponectin gene expression level by using sample b was significantly different from the adiponectin gene expression level by sample a, sample d, sample e, and sample f at a risk rate of less than 5%.

Further, the difference in the gene expression level of UCP-2 due to the pretreatment of 3T3-L1 cells (pretreatment with samples a to g) by the above quantification is as shown in Table 9 below. FIG. 6 is a graph showing the results.

From Table 9 and FIG. 6, it was confirmed that the sample b (procyanidin B2) as an example product exhibited the highest UCP-2 expression enhancing action in UCP-2 expression use. In particular, the gene expression level of UCP-2 by using sample b is significantly different from the gene expression level of UCP-2 by sample a, sample c, sample d, sample e, and sample f at a risk rate of less than 5%. Admitted.

From the above results, even when a compound very similar to procyanidin B2 in chemical structure, physical properties, etc., such as procyanidin B1 (sample c), is used as a sample for pretreatment of mature adipocytes. It can be seen that the PPAR-γ expression enhancing action, the adiponectin production promoting action, and the UCP-2 expression enhancing action as much as when procyanidin B2 (sample b) is used cannot be obtained.

Since the PPAR-γ expression enhancing action, adiponectin production promoting action, and UCP expression enhancing action are closely related to the prevention and improvement of obesity, diabetes and the like, it contains procyanidin B2, which is the product of this example, as an active ingredient. However, it is speculated that a drug capable of exerting each of the above-mentioned effects will have advantageous effects even when used as an anti-diabetic agent, anti-obesity agent, visceral fat accumulation reducing agent, or visceral fat accumulation inhibitor. Is done. Moreover, since these chemical | medical agents do not show a side effect substantially, they can also be contained in food-drinks.

The drug of the present invention contains procyanidin B2 as an active ingredient and has a PPAR-γ expression enhancing action, adiponectin production promoting action or UCP expression enhancing action, and exhibits these effects without showing any side effects. Is effective, so that it is excellent in safety and industrially useful. Further, based on these actions, it can be used as an antidiabetic agent, an antiobesity agent, a visceral accumulated fat reducing agent, a visceral fat accumulation inhibiting agent, or the like. Moreover, since the food / beverage products containing the said chemical | medical agent can be applied to all food / beverage products, it is industrially useful also in the meaning which gives a functional added value to food / beverage products. Furthermore, application to livestock and pet feed is also possible.

Claims (7)

A PPAR-γ expression enhancer comprising procyanidin B2 as an active ingredient and having a PPAR-γ expression enhancing action. An adiponectin production promoter characterized by containing procyanidin B2 as an active ingredient and having an adiponectin production promoting action. A UCP activator comprising procyanidin B2 as an active ingredient and having a UCP expression enhancing action. 4. The drug according to any one of claims 1 to 3, wherein the procyanidin B2 content is set in a range of 0.01 to 100% by weight. The drug according to any one of claims 1 to 4, wherein the daily procyanidin B2 intake is set to be in the range of 0.1 to 1000 mg. An anti-diabetic agent, an anti-obesity agent, a visceral accumulated fat reducing agent, or a visceral fat accumulation inhibiting agent comprising the drug according to any one of claims 1 to 5. A food or drink comprising the drug according to any one of claims 1 to 6.

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