JP7437731B2 - Pharmaceutical compositions and food and drink products for the prevention and treatment of lifestyle-related diseases - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act (1) The 31st Annual and International Meeting of the Japanese Association for Animal Cell Technology (JAACT2018 Tsu kuba) Program & Abstracts (31st Japanese Society for Animal Cell Engineering 2018 International Conference (JAACT2018 Tsukuba) Program and Publication date: November 5, 2018 (2) The 4th International Conference on Pharma and Food (ICPF2018) Program and Abstracts Publication date: 2012 Year 11 14th of the month

The present invention relates to pharmaceutical compositions for the prevention and/or treatment of various lifestyle-related diseases and health foods due to the differentiation of various cells and the metabolic regulating effect of a lignan compound derived from Piper Cubeba.

Lifestyle-related diseases are a group of diseases whose onset and progression are affected by lifestyle habits such as eating habits, exercise habits, rest, smoking, and drinking, and include obesity, diabetes, dyslipidemia, hyperuricemia, and hypertension. This includes periodontal disease, osteoporosis, etc., and is also closely related to pathological conditions such as arteriosclerosis, gout, kidney damage, and sarcopenia, and countermeasures are required. Tissues and organs important for controlling these diseases include adipose tissue, liver, and muscle. In addition, cells important for the onset and treatment of these diseases include fat cells, hepatocytes, and muscle cells, and biomolecules such as adiponectin and peroxisome proliferator-activated receptors. :PPAR), 5'adenosine monophosphate-activated protein kinase (AMPK), and xanthine oxidase.

Diabetes is mainly classified into type 1 diabetes, which is caused by decreased insulin secretion, and type 2 diabetes, which is caused by a weakening of the effect of insulin called insulin resistance. Pioglitazone, an agonist of the nuclear receptor PPARγ, is known as the main therapeutic drug for type 2 diabetes. PPARγ agonists such as pioglitazone are thought to induce adipocyte differentiation and production of adipokines such as adiponectin, increase insulin sensitivity, improve insulin resistance, and exert antidiabetic effects. Eicosanoids and the like are known as natural PPARγ agonists (Patent Document 1). Triterpene compounds derived from rice bran, Luo Hanguo, shimeji mushroom, chrysanthemum, and rye are known as naturally derived adiponectin production promoters, and are used as anti-arteriosclerotic agents, anti-obesity agents, anti-diabetic agents, and liver fibrosis inhibitors. It has been shown that it can be used (Patent Document 2).

Muscles are the main organs that take up and consume sugar, and are important in regulating blood sugar levels. In addition to insulin signals, AMPK signals are known to play an important role in glucose uptake in muscles. AMPK is a type of phosphorylating enzyme that is activated not only by exercise and adiponectin but also by starvation, and is an important enzyme responsible for energy regulation. Metformin, a biguanide drug that activates AMPK, is known to improve glucose tolerance and insulin resistance and exhibit antidiabetic and antiobesity effects by regulating glycolipid metabolism (Non-patent Literature 1). Naturally derived AMPK activators such as 5,7-dimethoxyflavone are known, and are useful for the prevention and treatment of glucose intolerance, hyperlipidemia, hypertension, coronary artery disease, arteriosclerotic disease, obesity, etc. It is useful for increasing muscle mass and strength (Patent Document 3). Activation of AMPK by adiponectin is involved in improving skeletal muscle function and is known to be useful in improving sarcopenia (Non-Patent Document 2). In addition, adiponectin suppresses gluconeogenesis in the liver through AMPK activation, and also suppresses fat synthesis and fat accumulation, thereby improving non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD). (Non-patent Document 3).

Nucleic acids and purines are metabolized in the liver and excreted as uric acid, but excessive intake or decreased excretion of purines can lead to hyperuricemia, in which the concentration of uric acid in the blood increases. If this hyperuricemia continues, urate crystals will be deposited in or around the joints, leading to the development of so-called gout symptoms such as acute arthritic attacks, gouty tophi, joint dysfunction, and joint deformation. It causes many complications such as disability and vascular disorders. Xanthine oxidase is an enzyme that catalyzes the conversion of hypoxanthine to xanthine and then to uric acid in nucleic acid metabolism, and allopurinol, an inhibitor of xanthine oxidase, is used as a treatment for gout. As a naturally occurring xanthine oxidase inhibitor, a blood uric acid level lowering agent containing pomegranate extract as an active ingredient is known (Patent Document 4).

Japanese Patent Application Publication No. 2000-355538 Japanese Patent Application Publication No. 2005-068132 Japanese Patent Application Publication No. 2017-031121 Japanese Patent Application Publication No. 2006-016340

Latest Medicine 70:632-639, 2015 Journal of the Japanese Geriatrics Society 55:13-24, 2018 Mebio 33:32-37, 2016

The present invention aims to address various lifestyle-related diseases (obesity, diabetes, hyperuricemia, dyslipidemia, etc.) and pathological conditions related to these diseases (gout, arteriosclerosis, non-alcoholic fatty liver, sarcopenia, renal disorder, etc.) ), as well as health foods and drinks, including adipocyte differentiation promoters, sugar uptake promoters, adiponectin production promoters, PPARγ activators, and AMPK activators. , to provide a uric acid production inhibitor.

The present inventors used fat cells, muscle cells, liver cells, etc., to search for natural materials with abundant dietary experience that would solve the above-mentioned problems. ) and Hinokinin activate PPARγ, induce adiponectin production, and promote sugar uptake in adipocytes, and activate AMPK and promote sugar uptake in muscle cells. The present invention was completed based on the discovery that the drug activates AMPK in hepatocytes, promotes sugar uptake, and suppresses uric acid production.

That is,
The present invention is as follows.
[1] A prophylactic and/or therapeutic agent for lifestyle-related diseases, which contains at least one or more of cubevin or hinokinin as an active ingredient.
[2] PPARγ activator containing at least one or more of cubevin or hinokinin as an active ingredient
[3] An adiponectin production promoter containing at least one of cubebin and hinokinin as an active ingredient.
[4] An AMPK activator containing at least one of cubevin or hinokinin as an active ingredient.
[5] A sugar uptake promoter containing at least one or more of cubevin or hinokinin as an active ingredient.
[6] A uric acid production inhibitor containing at least one or more of cubevin or hinokinin as an active ingredient.
[7] An insulin resistance improving agent containing any one of [1] to [6] as an active ingredient.
[8] A prophylactic and/or therapeutic agent for diabetes, which contains any one of [1] to [6] as an active ingredient.
[9] A prophylactic and/or therapeutic agent for hyperuricemia, which contains any one of [1] to [6] as an active ingredient.
[10] A prophylactic and/or therapeutic agent for sarcopenia containing any one of [1] to [6] as an active ingredient
[11] A lipid metabolism improving agent containing any one of [1] to [6] as an active ingredient
[12] A prophylactic and/or therapeutic agent for steatohepatitis containing any one of [1] to [6] as an active ingredient
[13] A method for preventing and/or treating lifestyle-related diseases, comprising:
A method comprising the step of administering the composition according to [1] to [12] containing at least one cubebin or hinokinin to humans and animals suffering from the above-mentioned diseases.

The preventive and/or therapeutic agent for lifestyle-related diseases of the present invention has a PPARγ activating effect, can promote adiponectin production, activate AMPK, and promote sugar uptake, and can also inhibit uric acid production. Can be suppressed. Therefore, it is possible to improve insulin resistance and regulate glycolipid metabolism, and to prevent and/or treat and improve obesity, diabetes, dyslipidemia, nonalcoholic steatohepatitis, sarcopenia, and arteriosclerosis. Can be used. It can also be used to prevent and/or treat and improve hyperuricemia, and can be used to prevent and/or treat and improve gout and renal disorders.

1 is a photograph of cells showing the effects of cubebin and hinokinin on fat accumulation, which is an indicator of adipocyte differentiation. It is a graph showing the effects of cubebin and hinokinin on fat accumulation, which is an indicator of adipocyte differentiation. It is a graph showing the effect of cubevin and hinokinine on mRNA expression of PPARγ and adiponectin in adipocytes. It is a graph showing the PPARγ ligand action of cubebin and hinokinin. 1 is a graph showing the effects of cubevin and hinokinine on sugar uptake by muscle cells, hepatocytes, and fat cells. FIG. 2 is a diagram showing the effects of cubebin and hinokinin on AMPK activation in hepatocytes. It is a graph showing the effect of cubebin and hinokinine on uric acid production in hepatocytes.

The prophylactic and/or therapeutic agent for lifestyle-related diseases of the present invention contains cubebin or hinokinin as an active ingredient. Qubebin has a structural formula shown in formula (1) below. Hinokinin has a structural formula shown in formula (2) below.

<Embodiment 1: Pharmaceutical composition>
According to the invention,
A pharmaceutical composition for preventing and/or treating lifestyle-related diseases is provided, which contains cubebin or hinoquinin, which is a compound represented by the above chemical formulas (1) to (2).
Cubevin or hinokinin may be used alone or may be blended in any proportion.
The pharmaceutical composition may contain pharmaceutically acceptable excipients, lubricants, binders, disintegrants, coating agents, and the like. It may also contain colorants, fragrances, preservatives, and the like. Examples of excipients include lactose, glucose, corn starch, sorbitol, crystalline cellulose, etc., lubricants include talc, magnesium stearate, polyethylene glycol, hydrogenated vegetable oil, etc., and binders include dimethyl cellulose, polyvinyl alcohol, etc. Polyvinyl ether, methylcellulose, ethylcellulose, gum arabic, gelatin, hydroxypropylcellulose, polyvinylpyrrolidone, etc., and examples of disintegrants include starch, sodium alginate, gelatin powder, calcium carbonate, calcium citrate, dextrin, etc. The form in which it is used is not particularly limited, and it can be in the form of capsules, powder, granules, tablets, liquid, etc. It can also be used as external preparations such as cream, paste, gel, etc., or as a sustained release patch. It can also be used in other forms.

<Embodiment 2: Composition for food and drink>
Cubebin or hinokinin of the present invention can be used as a supplement for preventing or improving lifestyle-related diseases, or can be mixed with food or drink or used as a composition for food or drink.
When used as a supplement, it can be used in the form of tablets or granules, and may be mixed with other useful ingredients.
When used as a food or drink composition, it can be provided as a health food or drink, a food or drink for specified health use, a food with functional claims, a food or drink with nutritional function, a health supplement food or drink, and the like. These foods and drinks can be served as functional foods that are useful for preventing and improving lifestyle-related diseases. It can display functions such as reducing blood sugar levels, improving lipid metabolism, improving sugar metabolism, suppressing increases in blood sugar levels, lowering uric acid levels, and maintaining healthy liver function.
The composition for food and drink can be in various forms such as solid, liquid, powder, granule, paste, etc. Specifically, for example, soft drinks, lactic acid drinks, recreational drinks, coffee, green tea, black tea, oolong tea, etc. beverages; confectionery such as candies, chocolates, biscuits, sweet breads, cakes, rice cakes, and rice cakes; processed vegetable and fruit products such as fruit drinks, vegetable drinks, jams, and pastes; sake, shochu, and wine Alcoholic beverages such as Chinese liquor, whiskey, vodka, brandy, gin, rum, liquor, beer, soft alcoholic beverages, fruit wine, and liqueurs; Dairy products such as yogurt, ice cream, butter, cheese, condensed milk, and powdered milk ; Oil and fat processed products such as dressings, mayonnaise, tempura oil, and salad oil; Seasonings such as soy sauce, sauce, vinegar, mirin, and dressing type seasoning; Powdered juice, powdered soup, instant coffee, instant noodles, instant curry, instant miso soup, Examples include dried foods and drinks such as cooked foods, cooked drinks, and cooked soups, processed grain products such as processed flour products, and processed starch products. For example, it may be used in solid form such as candy, cookies, chewing gum, and biscuits, or in liquid form such as soft drinks, milk, yogurt, and syrup. When used as food or drink, additives commonly used in food or drink, such as citric acid, lactic acid, and casein, can be added.

The pharmaceutical composition may be administered orally, or parenterally, such as intravenously, intramuscularly, subcutaneously, rectally, or transdermally.
The content of cubevin or hinokinine in pharmaceutical compositions containing cubevin or hinokinin, such as drugs, supplements, or food and drink compositions, varies depending on the dosage form, but usually cubevin or hinokinin is It may be contained in an amount of about 0.001 to 50% by weight, preferably about 0.01 to 20% by weight in the composition. In the case of cubevin or hinokinin, the intake amount can be increased or decreased as appropriate depending on the age, gender, weight, type of symptoms, and severity of the person taking it, but the daily intake amount is 0.01 to 300 mg/kg. It is preferable to set the dosage according to each dosage form so that the dosage is adjusted accordingly. Whether in the form of a pharmaceutical composition, an edible composition, or a biocompatible material, it may be administered or ingested once a day or in several divided doses.
The pharmaceutical composition, supplement, or composition for food or drink such as food or drink containing cubebin or hinokinin of the present invention is intended for mammals including humans. Mammals other than humans include primates such as monkeys, rodents such as rats and mice, sheep, pigs, cows, cats, and dogs.

<Embodiment 3: Method for preventing or treating lifestyle-related diseases>
According to the present invention,
A method for preventing or treating lifestyle-related diseases, the method comprising:
A method is provided that includes the step of administering a pharmaceutical composition or food or drink containing cubevin or hinokinin to a human or animal suffering from the above lifestyle-related disease.
When administering the above pharmaceutical composition to a patient, the dosage varies depending on various conditions such as the severity of the patient's symptoms, age, weight, PSA value, urine flow rate, and health condition. In general, it is sufficient to administer once or more times a day using the above-mentioned dosage and usage method, and the frequency and amount of administration may be increased or decreased as appropriate depending on the above-mentioned conditions.
The daily dosage, administration period, and number of administrations of the above-mentioned pharmaceutical composition or pharmaceutical preparation for prevention or treatment of lifestyle-related diseases may be the same as those for the above-mentioned therapeutic agent. Administration of the above-mentioned pharmaceutical composition or pharmaceutical preparation for prevention or treatment of lifestyle-related diseases may be terminated at the discretion of a physician or at the patient's own discretion.

Although the embodiments of the present invention have been described above, these are merely examples of the present invention, and various configurations other than those described above may also be adopted.

EXAMPLES Hereinafter, the present invention will be explained in more detail based on Examples, but the present invention is not limited thereto.

[Example 1] Effect on adipocyte differentiation
PPARγ activators are known to promote adipocyte differentiation. The effect on PPARγ activation was evaluated using fat accumulation, which increases with adipocyte differentiation, as an index.

3T3-L1 mouse preadipocyte cell line (obtained from JCRB cell bank) cells were seeded at 25,000 cells/well in a 24-well plate, cultured in 10% FBS-DMEM medium for 3 days, and then incubated in the presence of insulin (5 μg/mL). Cubevin or hinokinin was added at 10 μM and 30 μM and cultured for 6 days. Similarly, as a positive control (PC), rosiglitazone, a PPARγ agonist, was added at a concentration of 1 μM and cultured for 6 days. After culturing, the cells were fixed with a neutral buffered formalin solution, and intracellular lipid droplets were stained using oil red O staining and photographed and observed under an optical microscope (Figure 1). In addition, the amount of fat accumulation was quantified by dissolving Oil Red O dye and measuring the absorbance using a plate reader (Figure 2).

As a result of cell photo analysis, in the control culture cultured with only insulin, almost no red-stained lipid droplets were observed, whereas when 1 μM rosiglitazone was added, many red-stained lipid droplets were observed. (Figure 1). When cubebin (30 μM) or hinokinin (30 μM) was added, many red-stained lipid droplets were observed (Figure 1). Next, we extracted the oil red O dye taken up into intracellular lipid droplets and quantified the amount of fat accumulation. The results showed that compared to the control (CN) cultured with only insulin added, 1 μM of rosiglitazone was added. In the positive control (PC), the amount of fat accumulation was significantly increased (Figure 2). The amount of fat accumulation was also significantly increased in cells to which cubebin or hinokinin was added (FIG. 2). These results indicate that cubevin and hinokinin promoted adipocyte differentiation, which is thought to be a result of cubebin and hinokinin activating PPARγ.

[Example 2] Effect on gene expression of adipocytes
To confirm the PPARγ activation effect, we analyzed the effect on PPARγ gene expression in adipocytes. Furthermore, in order to clarify the effect on adiponectin production, the effect on adiponectin gene expression in adipocytes was analyzed. After culturing 3T3-L1 cells for 3 days in the presence of insulin (10 μg/mL) with cubevin or hinokinin (50 μM), total RNA was extracted using TRIzol reagent (Life Technologies Japan). cDNA was prepared from total RNA using a commercially available kit, and the mRNA expression levels of PPARγ and adiponectin were analyzed by real-time RT-PCR.

Analysis of relative mRNA expression levels revealed that cubevin and hinokinin promoted PPARγ mRNA expression in 3T3-L1 adipocytes (Figure 3). This indicates that cubevin and hinokinin promoted adipocyte differentiation and also had a PPARγ activating effect. Furthermore, cubevin and hinokinin were shown to strongly induce adiponectin mRNA expression in 3T3-L1 adipocytes (Figure 3). This indicates that cubevin and hinokinin strongly promote the production of adiponectin in adipocytes.

[Example 3] Analysis of PPARγ ligand activity
In order to examine the PPARγ agonist action, the PPARγ ligand activity of cubebin and hinokinin was evaluated using NuLigand kit (Microsystems) according to the attached protocol. 100 μl of the PPARγ solution was dispensed into each well of a 96-well plate, a plate seal was applied, and the plate was left standing at 4° C. overnight. After removing the PPARγ solution, wash with a buffer containing 0.5 μM DTT, add 100 μl of CBP-BAP solution to each well, and add positive control rosiglitazone, cubebin, or hinokinin. The mixture was left standing at 4°C for 1 hour. After washing with buffer, 100 μl of substrate solution (1M Tris-HCl (pH 8.0) solution containing NPP) was dispensed into each well, and after reacting at 37°C for 3 hours, 0.5N NaOH was added to each well. The reaction was stopped by adding 25 μl to each well, and the absorbance at 405 nm was measured.

As a result of the PPARγ ligand assay, compared to the control (CN), the addition of rosiglitazone, a PPARγ agonist, increased the absorbance in a concentration-dependent manner (FIG. 4). Similarly, compared to the control (CN), when cubebin or hinokinin was added, the absorbance increased in a concentration-dependent manner (Figure 4), indicating that cubebin and hinokinin have PPARγ agonist effects. It is shown that.

[Example 4] Effect on glucose uptake in rat-derived L6 muscle cells, human-derived HepG2 hepatocytes, and mouse-derived 3T3-L1 adipocytes Rat-derived L6 myoblasts (purchased from American Type Culture Collection) were treated with 10% FBS-DMEM ( Suspended in high glucose) medium and seeded at 5,000 cells/well in a 96-well plate, cultured for 2 days, exchanged to 2% FBS-DMEM (low glucose) medium, cultured for another 6 days, L6 It was made into muscle cells. Human-derived HepG2 cells (obtained from RIKEN BRC) were suspended in 10% FBS-DMEM (high glucose) medium, seeded in a 96-well plate at 20,000 cells/well, and cultured for 2 days. Mouse-derived 3T3-L1 cells were suspended in 10% CS-DMEM (high glucose) medium and seeded at 5,000 cells/well in a 96-well plate. After culturing for 3 days, isobutylmethylxanthine, dexamethasone, and insulin were added. The medium was changed to 10% FBS-DMEM (high glucose) and cultured for an additional 6 days to prepare 3T3-L1 adipocytes that had differentiated and accumulated fat. Each cell was incubated with KHH(-) buffer (glucose-free Krebs-Henseleit buffer containing 0.1% BSA, 10mM Hepes, and 2mM sodium pyruvate; pH 7.4, 141 mg/L MgSO4, 160 mg/L KH2PO4, After culturing for 2 hours in 350 mg/L KCl, 6,900 mg/L NaCl, 373 mg/L CaCl2・2H2O and 2,100 mg/L NaHCO3, KHH (+ ) buffer (KHH(-) buffer containing 11 mM glucose) and further cultured at 37°C for 6 to 20 hours. The glucose concentration in the culture solution before and after cultivation was measured using Glucose CII Test Wako (Wako Pure Chemical Industries, Ltd.), and the amount of decrease in glucose in the culture solution was calculated from the difference in glucose concentration before and after cultivation. The value was taken as the amount of sugar uptake by the cells.

In L6 muscle cells, a concentration-dependent increase in sugar uptake was observed when cultured with the addition of cubevin or hinokinin compared to the amount of sugar uptake in the control (CN) (Figure 5, A). . Similarly, when HepG2 hepatocytes were cultured with cubevin or hinokinin compared to the control (CN), a concentration-dependent increase in sugar uptake was observed (FIG. 5, B). Furthermore, when differentiated 3T3-L1 adipocytes were cultured with the addition of cubebin or hinokinin, a concentration-dependent increase in sugar uptake was observed compared to the control (CN) (Figure 5, C). These effects were observed in the absence of insulin, indicating that cubevin and hinokinin have the effect of promoting glucose uptake in muscle cells, hepatocytes, and fat cells in an insulin-independent manner. Ta. This also suggests that cubebin and hinokinin activate AMPK, an insulin-independent sugar uptake signaling pathway.

[Example 5] Effect on AMPK activation Activation of AMPK, which is important for glycolipid metabolism and energy metabolism, was investigated using Western blotting using the amount of phosphorylated AMPK (p-AMPK) as an indicator. Human-derived HepG2 cells were suspended in 10% FBS-DMEM (high glucose) medium, 1,000,000 cells were seeded in a 3.5 cm dish, and cultured for 2 days. After culturing in KHH(-) buffer for 2 hours, the culture was exchanged to KHH(+) buffer with or without cubevin or hinokinin, and further cultured at 37°C for 30 to 270 minutes. After culturing, cells were washed with ice-cold PBS and then treated with Complete Lysis-M reagent (Roche Diagnostics Ltd.) supplemented with the phosphatase inhibitor PhosSTOP (Roche Diagnostics Ltd.). The cells were lysed, the cell lysate was centrifuged at 14,000 xg for 5 minutes, and the supernatant was collected and used as a sample. Each sample was separated by SDS-PAGE according to a conventional method, transferred to a PVDF membrane and blocked, and then analyzed by Western blotting using an anti-phosphorylated AMPK antibody and an anti-AMPK antibody.

As a result of analyzing the amount of phosphorylated AMPK (p-AMPK) by Western blotting, it was found that when cultured with the addition of AICAR, an AMPK activating compound, control (CN ), the amount of phosphorylated AMPK was increased (Figure 6). When cultured with the addition of hinokinin, a similar increase in the amount of phosphorylated AMPK was observed after 30, 90, and 270 minutes (FIG. 6). Furthermore, when cultured with the addition of cubebin, the amount of phosphorylated AMPK was clearly increased compared to the control (Figure 6). The amounts of phosphorylated AMPK were CN(+), cubebin (++), hinokinin (+++), and AICAR (+++). At this time, no major changes were observed in the amount of AMPK in any case (Figure 6). This indicates that cubebin and hinokinine increased the amount of phosphorylated AMPK in human hepatocytes, indicating that cubebin and hinokinine have an AMPK activating effect.

[Example 6] Effect on uric acid production The effect on uric acid production was investigated using mouse-derived AML12 hepatocytes (obtained from ATCC). AML12 hepatocytes were suspended in DMEM/F-12 medium containing 10% fetal horse serum, ITS liquid medium supplement (Sigma-Aldrich), and dexamethasone, seeded in a 48-well plate at 62,500 cells/well, and cultured for 3 days. The medium was replaced with DMEM/F-12 medium containing % fetal horse serum, ITS liquid medium supplement (Sigma-Aldrich), and dexamethasone, and further cultured overnight. After that, in KHH(+) buffer containing 100 μM each of uric acid precursors guanosine and inosine, and with or without addition of xanthine oxidase inhibitor allopurinol, cubebin, or hinokinine as a positive control, After culturing for 4 hours, the uric acid concentration in the culture supernatant was measured using Uric Acid C-Test Wako (Wako Pure Chemical Industries, Ltd.), which is determined by uricase colorimetry, and the amount of uric acid produced was analyzed.

As a result of examining uric acid production in AML12 hepatocytes, uric acid production (CN) induced by guanosine and inosine was significantly suppressed by the addition of allopurinol as a positive control (PC) (FIG. 7). Furthermore, when cubebin or hinokinine was added, the amount of uric acid produced induced by guanosine and inosine was reduced in a concentration-dependent manner (FIG. 7). This shows that cubebin and hinokinin have a uric acid production suppressing effect, and are useful for preventing, improving, and treating hyperuricemia.

The present invention has been described above based on examples. Those skilled in the art will understand that this embodiment is merely an example, and that various modifications are possible and that such modifications are also within the scope of the present invention.

The prophylactic and/or therapeutic agent for lifestyle-related diseases containing cubevin or hinokinin as an active ingredient of the present invention is useful as a pharmaceutical preparation, functional food, supplement, etc. for the prevention, improvement, or treatment of lifestyle-related diseases in humans and animals. Yes, PPARγ activator, adiponectin production promoter, AMPK activator, glucose uptake promoter, uric acid production inhibitor, insulin resistance improving agent, antidiabetic agent, antihyperuricemic agent, antisarcopenic agent, lipid It is also useful as a metabolism improving agent and an anti-nonalcoholic steatohepatitis agent.

Claims (2)

A uric acid production inhibitor containing at least one of cubebin and hinokinin as an active ingredient. A prophylactic and/or therapeutic agent for hyperuricemia, which contains at least one of cubebin and hinokinin as an active ingredient.

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