Adiponectin secretion promoter

Abstract

The present invention provides an adiponectin secretion promoter containing a dried powder of marigold, preferably marigold leaves, and a food or drink containing the same for promoting adiponectin secretion.

Description

Technical Field

[0001] The present invention relates to an adiponectin secretion promoter.

Background Art

[0002] Cirsium brevicaule A. Gray is a plant belonging to the genus Cirsium of the Asteraceae family. Cirsium brevicaule A. Gray in Japan widely grows wild on the coasts of islands south of Kagoshima. Cirsium brevicaule A. Gray has traditionally been used not only as a food ingredient but also as a crude drug in the Okinawa Islands and the Amami Islands. The present inventors have reported that when Cirsium brevicaule A. Gray powder was simultaneously given to mice fed a high-fat diet, the blood fatty acid concentration decreased, the subcutaneous fat amount decreased, the liver fat amount decreased, and the expression of fatty acid synthase was suppressed (Patent Document 1, Non-Patent Document 1).

[0003] Adiponectin is a kind of cytokine (adipokine) secreted from adipocytes and is known as a good adipokine. Adiponectin is known to be closely related to lifestyle-related diseases such as cardiovascular diseases, diabetes, and obesity. When a high-fat diet is loaded on type 2 diabetic model mice, hypertrophy of adipocytes and aggravation of insulin resistance are induced, and at this time, the blood adiponectin concentration significantly decreases. On the other hand, when adiponectin is supplemented to obese type 2 diabetic model mice loaded with a high-fat diet, insulin resistance is improved (Non-Patent Document 2). Adiponectin gene-deficient mice exhibit various symptoms of metabolic syndrome such as insulin resistance, abnormal glucose tolerance, abnormal lipid metabolism, and hypertension. Therefore, it is considered that the decrease in adiponectin level due to obesity is at least partly the cause of impaired glucose tolerance, abnormal lipid metabolism, and hypertension.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005] [Non-Patent Document 1] Inafuku M, et al. Cirsium brevicaule A. GRAY leaf inhibits adipogenesis in 3T3-L1 cells and C57BL / 6 mice, Lipids Health Dis. 2013 Aug 15;12:124. [Non-Patent Document 2] Yamauchi T, et al., The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity, Nature med 7: 941-946, 2001. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] The present invention aims to provide a novel adiponectin secretion-promoting agent that is safe and low-toxicity, and can be administered over a long period of time. [Means for solving the problem]

[0007] To solve the above problems, the present invention includes the following inventions. [1] An adiponectin secretion promoter containing Cirsium japonicum. [2] The adiponectin secretion promoter according to [1], which contains dried powder of Cirsium japonicum. [3] Food and beverages for promoting adiponectin secretion containing the adiponectin secretion promoter described in [1] or [2] above. [Effects of the Invention]

[0008] The present invention provides a safe and low-toxicity adiponectin secretion promoter that is effective in humans and can be taken long-term. [Modes for carrying out the invention]

[0009] The inventors conducted a clinical trial involving 24 Japanese adult men and women whose LDL cholesterol levels were in the borderline or mild range (120-159 mg / dL) or whose triglyceride levels were in the high-normal range or slightly elevated range (120-199 mg / dL) in order to investigate the effects of thistle on human lipid metabolism. The results showed that after ingesting dried thistle powder three times a day (3g x 3 / day) for 12 weeks, blood adiponectin levels significantly increased at 8 and 12 weeks after ingestion. Therefore, it was revealed that thistle is useful as an active ingredient in an adiponectin secretion promoter.

[0010] The present invention provides an adiponectin secretion promoter containing Cirsium japonicum. Cirsium japonicum can be used after any number of cultivation days. The part used is not particularly limited and may be any of the leaves, stems, roots, rhizomes, fruits, seeds, seed coats, flowers, etc. Preferably, it is the leaves of Cirsium japonicum.

[0011] In the adiponectin secretion promoter of the present invention, the Japanese thistle may be used fresh or dried. It may also be used in the form of dried powder, freeze-dried powder, juice, extract, etc. The Japanese thistle can be dried by known drying methods such as natural drying, hot air drying, cold air drying, reduced pressure drying, or freeze-drying. Powdering can be done by, for example, crushing the dried Japanese thistle using a commercially available pulverizer and then removing the non-powdered material. Juicing can be done using a commercially available juicer. The extract can be obtained by performing an extraction operation on the Japanese thistle using a solvent. The Japanese thistle used in the extraction operation may be fresh Japanese thistle that has been finely chopped or crushed, or dried Japanese thistle that has been crushed or powdered.

[0012] The solvent used for extraction may be water, alcohols, hexane, chloroform, ethers, esters, or ketones. Examples of alcohols include ethanol, methanol, n-propanol, isopropanol, n-butanol, 1,3-butylene glycol, propylene glycol, and glycerin. Examples of ethers include diethyl ether and propyl ether. Examples of esters include butyl acetate and ethyl acetate. Examples of ketones include acetone and ethyl methyl ketone. A mixed solvent combining two or more of these solvents may also be used. Furthermore, different solvents may be used sequentially in the extraction operation, for example, by performing an extraction operation with hexane, followed by an extraction operation with chloroform on the resulting residue.

[0013] The extract from the Japanese thistle may be in any of the following states: as an extract, as a concentrated or diluted extract, as a solidified extract, or as a dried powder.

[0014] The adiponectin secretion promoter of the present invention may contain dried powder of Cirsium japonicum, freeze-dried powder of Cirsium japonicum, dried powder of Cirsium japonicum leaves, or freeze-dried powder of Cirsium japonicum leaves. Such dried powders and freeze-dried powders can be produced by known methods. Freeze-dried powder of Cirsium japonicum leaves can be produced, for example, by the method described in the examples.

[0015] The adiponectin secretion promoter of the present invention can significantly increase the blood adiponectin concentration, and is therefore suitably used as a pharmaceutical or food product for improving insulin resistance (Non-Patent Literature 2), alleviating liver damage (Fukushima J, et al., Hepatol Res. 2009 Jul;39(7):724-738), and suppressing liver fibrosis (Kamada Y et al., Gastroenterology. 2003 Dec;125(6):1796-807), for which adiponectin supplementation is known to be effective.

[0016] The adiponectin secretion promoter of the present invention can be used for the treatment or improvement of hypoadiponectinemia. Here, hypoadiponectinemia refers to a condition in which improvement in health is expected by promoting adiponectin secretion in the body.

[0017] Furthermore, the adiponectin secretion-promoting agent of the present invention can be used to treat or improve conditions and diseases caused by low adiponectin levels. For example, it can be used to treat or improve metabolic syndrome, lifestyle-related cancers, insulin resistance syndrome, diabetes (including type 1 and type 2 diabetes), diabetic complications (including retinopathy, renal dysfunction, neuropathy, cataracts, coronary artery disease, etc.), arteriosclerosis, coronary artery disease, renal dysfunction, myocardial infarction, hypertension, cerebrovascular disease, hyperlipidemia, hypercholesterolemia, obesity, decreased bone density, liver disease, etc. Moreover, the adiponectin secretion-promoting agent of the present invention can also be used for anti-aging purposes.

[0018] The adiponectin secretion promoter of the present invention can be implemented in the form of a pharmaceutical product. The pharmaceutical product of the present invention contains Cirsium japonicum as the active ingredient and can be formulated according to conventional methods. For example, formulations for oral administration include solid or liquid dosage forms, specifically tablets (including sugar-coated tablets and film-coated tablets), pills, granules, powders, capsules (including soft capsules), syrups, emulsions, and suspensions. These formulations are manufactured by known methods and contain carriers, diluents, or excipients commonly used in the pharmaceutical field. For example, lactose, starch, sucrose, and magnesium stearate are used as carriers and excipients for tablets. Formulations for parenteral administration include, for example, injections and suppositories, and injections include dosage forms such as intravenous injections, subcutaneous injections, intradermal injections, intramuscular injections, drip infusions, and intra-articular injections. Such injections are prepared according to known methods, for example, by dissolving, suspending, or emulsifying the above active ingredient in a sterile aqueous or oily solution commonly used for injections. For injection, aqueous solutions such as physiological saline, isotonic solutions containing glucose or other adjuvants may be used, and may be used in combination with appropriate solubilizers, such as alcohol (e.g., ethanol), polyalcohol (e.g., propylene glycol, polyethylene glycol), or nonionic surfactants (e.g., polysorbate 80, HCO-50). For oily solutions, sesame oil or soybean oil may be used, and may be used in combination with solubilizers such as benzyl benzoate or benzyl alcohol. Suppositories used for rectal administration are prepared by mixing the above active ingredients with a standard suppository base.

[0019] The adiponectin secretion promoter of the present invention can be implemented in the form of food and drink products. Food and drink products include health foods, functional foods, foods for specified health use, foods for patients, dietary supplements, etc. The form of food and drink products is not particularly limited. For example, beverages such as tea beverages, soft drinks, carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, etc., noodles such as buckwheat noodles, udon noodles, Chinese noodles, instant noodles, etc., candies, candies, gums, chocolates, snack foods, biscuits, jellies, jams, creams, baked confectioneries, breads, etc., processed fishery and livestock products such as kamaboko, ham, sausages, etc., dairy products such as processed milk, fermented milk, etc., oils and fats and oil-processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing, etc., seasonings such as sauces, gravies, etc., retort pouch foods such as curry, stew, donburi, rice porridge, mixed rice, etc., frozen confections such as ice cream, sherbet, shaved ice, etc. Dietary supplements can be provided in the form of, for example, tablets, granules, powders, drink agents, etc.

[0020] The pharmaceutical product for improving insulin resistance containing the adiponectin secretion promoter of the present invention or the food and drink product for promoting adiponectin secretion containing the adiponectin secretion promoter of the present invention contains as an active ingredient the Japanese thistle, which has been traditionally used as a food material, and thus can be safely used for humans and non-human mammals (for example, rats, mice, rabbits, sheep, pigs, cows, cats, dogs, monkeys, etc.).

[0021] The dosage or intake amount of the above-mentioned pharmaceuticals and foodstuffs can be determined depending on the age and weight of the patient or consumer, symptoms, administration time, dosage form, administration method, combination of drugs, etc. For example, when orally administering the adiponectin secretion promoter of the present invention as a medicine, per adult per day, as the dry powder of thistle, 0.1 g or more, 0.2 g or more, 0.3 g or more, 0.4 g or more, 0.5 g or more, 0.6 g or more, 0.7 g or more, 0.8 g or more, 0.9 g or more, 1.0 g or more may be administered, and 20 g or less, 18 g or less, 16 g or less, 15 g or less, 14 g or less, 13 g or less, 12 g or less, 11 g or less, 10 g or less may be administered. The administration may be carried out in multiple doses (for example, 3 times) per day.

[0022] When ingesting the adiponectin secretion promoter of the present invention as a foodstuff, per adult per day, the dry powder of thistle may be formulated so that the intake amount is 0.1 g or more, 0.2 g or more, 0.3 g or more, 0.4 g or more, 0.5 g or more, 0.6 g or more, 0.7 g or more, 0.8 g or more, 0.9 g or more, 1.0 g or more, or may be formulated so that the intake amount is 20 g or less, 18 g or less, 16 g or less, 15 g or less, 14 g or less, 13 g or less, 12 g or less, 11 g or less, 10 g or less. It may be ingested in multiple doses (for example, 3 times) per day.

Examples

[0023] Hereinafter, the present invention will be described in detail by way of examples, but the present invention is not limited thereto.

[0024] [Example 1: Influence of thistle on human lipid metabolism] <Test method> (1) Subjects Japanese men and women aged 20 to 80 years old at the time of obtaining consent, with LDL cholesterol values in the borderline and mild ranges (120 - 159 mg / dL), or triglyceride values in the normal high and slightly elevated ranges (120 - 199 mg / dL), 24 people were used as subjects.

[0025] (2) Preparation and ingestion of thistle After washing the leaves of the Japanese thistle with water, they were sterilized with hypochlorous acid. Then, they were thoroughly drained and pre-frozen. Next, the Japanese thistle leaves were freeze-dried using a vacuum drying device (Marui Co., Ltd.). The freeze-dried leaves were crushed in a pulverizer, sieved to remove non-powdered material, and obtained freeze-dried Japanese thistle leaf powder. The subjects ingested 3g of Japanese thistle powder three times a day (9g / day) for 12 weeks. Specifically, 3g of Japanese thistle powder was mixed with water (100-150mL) to prepare Japanese thistle green juice for consumption.

[0026] (3)Measurement items • Physical measurements: Height (first time only), weight, body fat percentage • General biochemical tests: glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides • Blood adiponectin ·Free fatty acids

[0027] BMI was calculated using the following formula: BMI = Weight (kg) ÷ Height (m) 2 Glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were measured by LSI Medience Corporation. Adiponectin levels were measured using the Human Adiponectin ELISA Kit (Otsuka Pharmaceutical). Free fatty acids were measured using the NEFA C-Test Wako (Wako Pure Chemical Industries).

[0028] (4) Exam Schedule Physical measurements and blood samples (8 mL) were taken before starting intake of thistle juice, 4 weeks after intake, 8 weeks after intake, and 12 weeks after intake, and each item was measured.

[0029] <Result> Table 1 shows the results of paired t-tests (mean ± standard deviation) comparing measurements at each time point to pre-intake measurements as a baseline. Body weight, BMI, triglycerides, free fatty acids, and fasting blood glucose levels remained unchanged. Body fat percentage significantly increased 8 and 12 weeks after the start of intake. Total cholesterol significantly increased 12 weeks after the start of intake. HDL cholesterol significantly increased 4, 8, and 12 weeks after the start of intake. LDL cholesterol significantly increased 8 and 12 weeks after the start of intake. HbA1c significantly increased 4 and 12 weeks after the start of intake. Adiponectin significantly increased 8 and 12 weeks after the start of intake.

[0030] [Table 1]

[0031] It should be noted that the present invention is not limited to the embodiments and examples described above, and various modifications are possible within the scope of the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention.

Claims

1. A human adiponectin secretion promoter containing dried powder of thistle leaves as an active ingredient, characterized in that at least 9 g of dried powder of thistle leaves is ingested per day for 8 weeks or more.

2. An adiponectin secretion promoter according to claim 1, for the treatment of hypoadiponectinemia in humans.

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