CN102844042A - Novel use of polygonatum falcatum or polygonatum sibiricum extract - Google Patents

Abstract

The present invention relates to a novel use of a Polygonatum falcatum or Polygonatum sibiricum extract for preventing and treating obesity or metabolic syndrome, and more specifically, to a pharmaceutical or food composition containing a Polygonatum falcatum or Polygonatum sibiricum extract for preventing and treating obesity, obesity complications or metabolic syndrome, a novel use of a Polygonatum falcatum or Polygonatum sibiricum extract for preparation of a medicine for preventing and treating obesity, obesity complications or metabolic syndrome, and a method for treating obesity, obesity complications or metabolic syndrome by using the extract.; The Polygonatum falcatum or Polygonatum sibiricum extract suppresses differentiation of fat cells and maintains SIRT1 at a high level, thereby reducing body weight, abdominal fat and glucose tolerance, and thus can be helpfully used to prevent and treat obesity, obesity complications or metabolic syndrome.

Description

New application of Polygonatum falciparum or Polygonatum angustifolia extract

technical field

This application is based on Korean Patent Application No. 10-2010-0032921 filed on April 9, 2010 and Korean Patent Application No. 10-2010-0095987 filed on October 1, 2010. Invention References.

The present invention relates to a new application of Polygonatum or Polygonatum angustifolia extract, in particular to a compound containing Polygonatum or Polygonatum as an active ingredient to maintain a high level of SIRT1 protein in cells, reduce body weight, reduce abdominal fat or improve glucose tolerance The pharmaceutical or food composition for the prevention and treatment of obesity, obesity complications or metabolic syndrome, and the prevention and treatment of obesity, obesity complications or metabolic syndrome, as well as the treatment method.

Background technique

With the advancement of medicine and the improvement of living standards, the average life expectancy has been extended, and the amount of exercise has been reduced due to the increase in the population living in cities. As a representative adult metabolic disease, the proportion of obesity is increasing significantly. At the same time, high blood pressure, abnormal lipid metabolism, and hyperglycemia caused by increased insulin resistance are on the rise. According to this, people with type 2 diabetes and its complications, myocardial infarction caused by arteriosclerosis, stroke and other fatal diseases The number of patients is on the rise.

Metabolic syndrome (Metabolic Syndrome) is a disease group that conceptualizes the phenomenon that various cardiovascular diseases and type 2 diabetes risk factors form groups with each other. A useful concept that encompasses the description of insulin resistance and the complex and diverse range of metabolic abnormalities and clinical states associated with it. When metabolic syndrome is present, the risk of cardiovascular disease or type 2 diabetes increases. Although this symptom has been known for a long time, in 1988, Reaven claimed that the common cause of these symptoms is insulin resistance due to poor insulin action in the body, and named it Syndrome X, insulin resistance syndrome. In 1998, the World Health Organization replaced the term "insulin resistance syndrome" and decided to call it "metabolic syndrome" because there was no conclusive evidence that insulin resistance could fully explain all the elements of the symptom.

The cause of metabolic syndrome is that even though there is insulin in the body, high blood sugar is not improved due to its resistance, resulting in an increase in insulin concentration. Excessive secretion of insulin to lower blood sugar can not regulate blood sugar to normal, resulting in proliferation of vascular cells, thickening of blood vessel walls, or promoting the reabsorption of sodium by the kidneys, resulting in increased blood pressure, and can also promote fat decomposition. At the same time of neutral fat, it reduces high-density cholesterol (HDL-cholesterol), and at the same time, it promotes the storage of fat components in the internal organs. Such as the interaction of these factors will lead to disease. Diabetes caused by abnormal blood glucose metabolism, increased neutral fat caused by abnormal lipid metabolism, high blood pressure caused by increased high-density cholesterol/sodium content, gout caused by increased uric acid, etc. all belong to this category. The cause of this insulin resistance is not yet clear, but it is known that abdominal obesity is the most influential factor, and excessive psychological stress and aging are also the causes. In addition, insulin resistance has been considered as a single cause of metabolic syndrome in the past, but recently, in addition to insulin resistance, obesity, adipocyte disorders, and the combined effects of various factors of metabolic syndrome have been added, and it is speculated that it is three main causes .

Metabolic syndrome was judged according to the following criteria. According to the standards of the US NCEP (National Cholesterol Education Program) published in 2001, abdominal obesity with a waist circumference of 40 inches (102cm) for men and 35 inches (88cm) for women, neutral fat (triglycerides) above 150mg/dL, and HDL cholesterol for men 40mg/dL dL, female below 50mg/dL, blood pressure above 130/85mmHg, fasting glucose (fasting glucose) above 110mg/dL, among these five risk factors, if a patient has more than three, it is judged as metabolic syndrome. A recent research report pointed out that for Orientals, a waist circumference of 90 cm for men and 80 cm for women is classified as abdominal obesity. If this rule is used, about 25% of the total population of Korea will show symptoms of metabolic syndrome.

Due to population aging and environmental changes, the incidence and prevalence of metabolic syndrome have increased sharply, resulting in not only a very high mortality rate, but also a high incidence of complications, resulting in huge economic and social losses. However, most of the drugs currently used are not only low in efficacy, but also have a high incidence of side effects when taken for a long time. In terms of improving the quality of life, there is an urgent need to develop therapeutic drugs.

At present, in developed countries including the United States, Europe and Japan, it is estimated that there are more than 300 million obese people, and in developing countries, it is also increasing by more than 1% every year, so the proportion of obese people in the world is on the rise. Even the World Health Organization (WHO) defines obesity as a "disease requiring treatment." As far as the United States is concerned, obesity is the second leading cause of indirect death after smoking, and the annual expenditure for this is more than 110 billion U.S. dollars. The economic burden is heavy and it has a very profound impact on society.

Worldwide patent applications related to obesity treatment agents showed an increasing trend from 1999 to 2004, especially in the United States, which showed a sharp increase during this period. The development has little effect. About 90% of obesity-related patents are related to appetite suppression, diet regulation, and fat metabolism, but recently the share of patents related to the regulation of fat proliferation and energy metabolism has gradually increased. Xenical) or Reductil (Reductil) and the limitations of existing obesity therapeutic agents and the necessity of improving and developing new mechanism obesity therapeutic agents.

SIRT1 is known as the mammalian homologue (~110kD) of Sirtuins (Sir2-related enzymes) proteins that cause lifespan-prolonging effects in yeast, and belongs to class III histone deacetylases that require NAD+ as a cofactor kind. So far, there are seven types of sirtuins found in animals, ranging from SIRT1 to SIRT7. They differ from each other in point of action and function. Among them, SIRT1 is activated in the nucleus and regulates the activity of various substrates related to metabolism, inflammation and degenerative brain diseases.

When food is restricted, the expression and activity of SIRT1 increase in various tissues such as liver, fat, and pancreas in vivo, and transcription factors such as PPARγ and FOXO1, and mitochondrial (Mitochondria) such as UCP1, UCP2, and UCP3 are related to energy metabolism. Direct deacetylation of proteins or deacetylation of co-regulators (coregulators) such as p300, NcoR, and PGC1α lead to indirect activity regulation. Therefore, not only prevent glycolysis in the liver, but also reduce fat accumulation in adipose tissue. In the pancreas, insulin sensitivity is increased, and, in muscle tissue, energy metabolism is increased, thereby causing weight loss through heat dissipation.

A decrease in the demand for therapeutic agents is currently occurring amidst a sharp increase in the obese population. This is in view of dissatisfaction with the side effects and efficacy of existing drugs, and thus it is urgent to develop novel obesity therapeutic agents that can overcome such problems.

Therefore, if a drug that can increase the expression and activity of SIRT1 in the body is developed instead of dietary restriction such as vegetarianism, it may be used as a new therapeutic agent for obesity and obesity complications.

Contents of the invention

technical issues

In the course of research on natural substances that increase the activity of SIRT1, the inventors found that the extract of Polygonatum falciparum or Polygonatum angustifolia of the present invention can increase the activity of SIRT1, explaining its effect on obesity, obesity complications or metabolic syndrome effect, thereby completing the present invention.

Therefore, the object of the present invention is to provide a new application of the Polygonatum plant extract as Polygonatum falciparum or Polygonatum angustifolia.

Technical solutions

In order to achieve the above object, the present invention provides a prevention and treatment of one or more diseases selected from the group consisting of obesity, obesity complications and metabolic syndrome, which contains the extract of Polygonatum falciparum or Polygonatum angustifolia as an active ingredient Pharmaceutical compositions used.

In order to achieve another object of the present invention, the present invention provides a prevention and treatment of more than one disease selected from the group consisting of obesity, obesity complications, and metabolic syndrome, which comprises Polygonatum falciparum or Polygonatum angustifolia extract as an active ingredient. A food composition for relief.

In order to achieve another object of the present invention, the present invention provides a use of Polygonatum falcatum (Polygonatum falcatum) or Polygonatum sibiricum (Polygonatum sibiricum) plant extract, for the preparation of obesity, obesity complications and metabolic syndrome Preparations for the prevention and treatment of one or more diseases selected from the group consisting of.

In order to achieve another purpose of the present invention, the present invention provides a method for preventing and treating more than one disease selected from the group consisting of obesity, obesity complications and metabolic syndrome, characterized in that: Polygonatum falciparum (Polygonatum falcatum) or Polygonatum sibiricum (Polygonatum sibiricum) is administered to an individual in need thereof in an effective dose.

The present invention will be described in detail below.

The composition of the present invention contains the extract of Polygonatum falciparum or Polygonatum angustifolia as an active ingredient, and can be used for the prevention and treatment of one or more diseases selected from the group consisting of obesity, obesity complications or metabolic syndrome.

In particular, the composition of the present invention can use Polygonatum falcatum (Polygonatum falcatum) or Polygonatum sibiricum (Polygonatum sibiricum) extract, more preferably the extract of Polygonatum falcatum or Polygonatum sibiricum rhizome as an active ingredient. In the present invention, Polygonatum sibiricum (Polygonatum sibiricum) recorded as Polygonatum angustifolia is also called Polygonatum sibiricum Delar, Polygonatum sibiricum Redout or Polygonatum sibiricum Redt. Polygonatum includes these plants. On the other hand, the extract of the present invention may be a Polygonatum extract. Polygonatum falcatum in the present invention belongs to the rhizome part of Polygonatum falcatum or Polygonatum angustifolia, more preferably, Polygonatum falcatum in the present invention belongs to the rhizome of Polygonatum falcatum called Chen Huangjing.

The Polygonatum falciparum or Polygonatum angustifolia extract of the present invention can be extracted by means of a known solvent extraction method. For example, it is possible to use water, and alcohols containing 1 to 6 carbons such as ethanol/alcohol/methanol/propanol/isopropanol/butanol from S. , acetone, diethyl ether, chloroform, ethyl acetate, dichloromethane, hexane, cyclohexane, petroleum ether (petroleum ether), diethyl ether, benzene organic solvents or any one of them or their mixed solvents extract. In particular, extraction is performed using one or more solvents selected from the group consisting of ethanol, alcohol, acetone, ethyl acetate, or methylene chloride, or mixing these solvents with other known solvents.

The Polygonatum falciparum or Polygonatum angustifolia extract of the present invention is extracted by means of solvent extraction and can be used directly, or in order to remove impurities and increase the concentration of active ingredients, it can be further separated and extracted by known methods. In order to improve the extraction efficiency, the extract can be concentrated under reduced pressure. As the solvent required for further extraction and extraction, water, one-carbon alcohol to six-carbon alcohol such as ethanol and methanol, ethyl acetate, dichloromethane, three Any one selected from organic solvents such as methyl chloride, n-Hexane, diethyl ether, acetone, and benzene, or their mixed solvents, especially water, n-butanol, ethanol, and ethyl acetate Choose any one or their mixed solvent for extraction and separation. The extracted extract can be used directly or subjected to further re-extraction extraction, when re-isolation, preferably, ethyl acetate can be used. In particular, in order to carry out the extraction process more economically, it is preferable to perform primary extraction with a single solvent or a mixed solvent, and it is preferable to use water, an alcohol having 1 to 6 carbon atoms such as ethanol and methanol, ethyl acetate, dichloromethane, dichloromethane , chloroform, n-Hexane (n-Hexane), diethyl ether, acetone, benzene organic solvents selected any one or their mixed solvents. More preferably, ethanol, alcohol, acetone, ethyl acetate, and dichloromethane can be used. Especially when alcohol is used as the extraction solvent, it can shorten the separation process of the extract, so it is most suitable.

In one embodiment of the present invention, after the various samples of 10g are finely pulverized, impregnate with 30ml of 100% methanol, extract repeatedly 3 times at normal temperature, extract 24 hours each time, utilize filtering device to filter the extraction solution, Methanol was removed using a decompression device to obtain a methanol extract. To the methanol extract obtained by the above process, 20 ml of ethyl acetate and 20 ml of water were respectively added, and after mixing, the upper layer was concentrated to obtain the ethyl acetate extract. As a result of measuring the SIRT1 expression increasing performance of the prepared extract, it was found that the SIRT1 expression was higher in the ethyl acetate extract of the present invention (refer to Example 1). In another embodiment of the present invention, a higher expression of SIRT1 was also found in the extraction solution obtained by directly immersing and extracting each sample with 80% ethanol (refer to Example 5).

The composition of the present invention is excellent in the efficacy of preventing and treating obesity, obesity complications or metabolic syndrome.

Obesity refers to the state of excess body fat. Complications of obesity refer to metabolic syndromes that arise as a result of a long-term obese state. Metabolic Syndrome (Metabolic Syndrome) refers to a syndrome in which risk factors such as hyperlipidemia, hypercholesterolemia, hypertension, abnormal glucose metabolism, coagulation defects, and obesity appear simultaneously.

This efficacy of the present invention is confirmed by in vivo and in vitro experiments.

In another aspect, the composition of the present invention has the effect of increasing the level of SIRT1 in vivo. SIRT1 refers to the mammalian homologue (~110kD) of Sirtuins (Sir2-related enzymes) proteins that cause lifespan-extending effects in yeast, and belongs to class III histonedeacetylases that require NAD+ as a cofactor.

In one embodiment of the present invention, through an in vivo experiment, it was found that the composition of the present invention has the effect of increasing the level of SIRT1. The amount of SIRT1 protein in muscle, liver and fat cells was measured after the administration of the composition administration group mice of the present invention and control group mice, and as a result, it was found that the amount of SIRT1 was increased in fat and muscle (see Example 2).

In addition, in one embodiment of the present invention, high-fat obesity diet was supplied to mice to make obesity models, and changes in body weight and abdominal fat were observed after administration of the composition of the present invention. As a result, it was found that the composition-administered group of the present invention had a reduction in body weight and a corresponding decrease in the size and amount of fat in the abdomen, although there was no difference in the amount of feed intake compared to the group given only the obese feed. In addition, glucose tolerance caused by insulin resistance, blood total cholesterol, neutral fat, free fatty acid values and related indicators of metabolic syndrome in tissues were measured. As a result, it was found that in the animals of the composition group of the present invention, the sugar tolerance could be improved by more than 60% (referring to Example 6), and cholesterol, neutral fat and free fatty acid were respectively reduced by more than 27.8%, 27.0%, and 38.2% (referring to Example 3 ).

Therefore, it was confirmed that the composition of the present invention has remarkable efficacy for the prevention and treatment of obesity, obesity complications, and metabolic syndrome.

The composition of the present invention not only exhibits the above effects, but also has minimal side effects on the human body compared with chemically synthesized drugs because the natural medicinal material extract is used as an active ingredient.

Therefore, it can be known that the extract of Polygonatum falciparum or Polygonatum angustifolia of the present invention inhibits adipocyte differentiation, maintains a high level of SIRT1, reduces abdominal fat and significantly reduces body weight in a high-fat food fattening mouse model, and has preventive and therapeutic effects. The role of obesity, obesity complications, or metabolic syndrome.

Therefore, the present invention provides a pharmaceutical composition for the prevention and treatment of obesity, obesity complications or metabolic syndrome, which contains Polygonatum falciparum or Polygonatum angustifolia extract as an active ingredient.

The pharmaceutical composition of the present invention may contain a pharmaceutically effective dose of Polygonatum falciparum or Polygonatum angustifolia extract alone, or additionally contain more than one pharmaceutically acceptable carrier. The pharmaceutical composition of the present invention can be administered to patients by a single dose, or by a fractionated treatment protocol of multiple doses for long-term administration. The above-mentioned so-called pharmaceutically effective dose refers to an amount that exhibits a higher response than that of the negative control group, and preferably refers to an amount sufficient for treating or preventing obesity. The effective dose of Polygonatum falciparum or Polygonatum angustifolia extract of the present invention is 0.001 to 1000 mg/day/kg body weight, but not limited thereto. However, the above-mentioned pharmaceutically effective dose can be appropriately changed according to various factors such as the disease and its severity, the patient's age, body weight, health status, sex, route of administration, and course of treatment.

The composition of the present invention, together with the above-mentioned pharmaceutically acceptable carrier, can be made into various dosage forms according to the route of administration by methods known in the industry. The route of administration may be oral or parenteral, but not limited thereto. The parenteral administration route includes, for example, various routes such as transdermal, nasal, intraperitoneal, intramuscular, subcutaneous, or intravenous.

When the pharmaceutical composition of the present invention is administered orally, it can be prepared into powder, granules, tablets, pills, sugar-coated tablets, capsules, liquids, gels, etc. Dosage forms such as elixirs, syrups, suspensions, and flakes. Suitable carriers include, for example, sugars including lactose/glucose/sucrose/sorbitol/mannitol/xylitol/erythritol and maltitol, and sugars including corn starch/wheat starch/rice starch and potato starch. Starches such as cellulose/methylcellulose/sodium carboxymethylcellulose and hydroxypropylmethylcellulose, and fillers such as gelatin/polyvinylpyrrolidone. In addition, cross-linked polyvinylpyrrolidone, agar, alginic acid, sodium alginate, or the like may be added as a disintegrant depending on the case. Furthermore, the above-mentioned pharmaceutical composition may additionally contain anticoagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like.

In addition, in the case of parenteral administration, the pharmaceutical composition of the present invention can be formulated together with a suitable parenteral carrier in the form of injections, transdermal agents, and nasal inhalants according to methods known in the industry. When preparing the above-mentioned injection, it must be sterilized to protect it from microorganisms such as bacteria and fungi. When making injections, examples of suitable carriers include water, ethanol, polyhydric alcohols (such as glycerin, propylene glycol, and liquid polyethylene glycol, etc.), mixtures thereof, and/or solvents or dispersion media containing vegetable oils , but not limited to this. More preferably, as a suitable carrier, such as Hank's solution, Ringer's solution, PBS (phosphate buffered saline) containing triethanolamine or sterile water for injection, isotonic solution of 10% ethanol, 40% propylene glycol and 5% glucose can be used wait. In order to protect the above-mentioned injections from contamination by microorganisms, various antibacterial and antifungal agents such as paraben, chlorobutane, phenol, sorbic acid, thimerosal, etc. can be added. In addition, the above-mentioned injections may contain isotonic agents such as sugar or sodium chloride in most cases. Transdermal agents include ointments, creams, lotions, gels, liquids for external use, pastes, liniments, aerogels, and the like. The above "transdermal administration" refers to the topical administration of the pharmaceutical composition to the skin, and the effective dose of active ingredients contained in the pharmaceutical composition is delivered into the skin.

These dosage forms are generally described in the well-known pharmacopoeia literature (Remington's Pharmaceutical Science, 15th Edition, 1975, Mack Publishing Company, Easton, Pennsylvania) in terms of pharmaceutical chemistry.

For administration by inhalation, the compounds used in the present invention may be administered from a pressure pack device or from a suitable propellant such as dichlorofluoromethane, trichlorofluoroethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. Conveniently delivered in the form of a mist in a nebuliser. In the case of a pressurized nebulizer, the dosage unit may be determined by a valve delivering a metered amount. For example, gelatin capsules and tubes for use in an inhaler or insufflator may be formulated to contain a powder mix of the compound and a suitable powder base such as lactose or starch.

In addition, for pharmaceutically acceptable carriers, reference can be made to the following literature (Remington's Pharmaceutical Sciences, 19th ed., 1995, Mack Publishing Company, Easton, PA). Preferably, it can contain 0.001-99.999% by weight of the pharmaceutical composition of the present invention and 99.999-0.001% by weight of a pharmaceutically acceptable carrier.

Furthermore, the pharmaceutical composition of the present invention can be administered in parallel with known compounds that have the effect of preventing and treating obesity, obesity complications, or metabolic syndrome.

Furthermore, the Polygonatum falciparum or Polygonatum angustifolia extract of the present invention may be provided in the form of a food composition for the purpose of improving obesity, obesity complications, or metabolic syndrome. The food composition of the present invention includes all forms of functional food, nutritional supplement, health food and food additives. The food composition of the above type can be prepared in various forms according to common methods known in the industry.

For example, as a health food, the Polygonatum falciparum or Polygonatum angustifolia extract itself can be prepared in the form of tea, fruit juice and beverage for drinking, or made into granules, capsules and powdered for intake. In addition, the Polygonatum falciparum or Polygonatum angustifolia extract of the present invention can be mixed with known substances or active ingredients known to have the effect of improving obesity, obesity complications or metabolic syndrome, and prepared in the form of a composition.

In addition, as functional food, it can be used in beverages (including alcoholic beverages), fruits and their processed foods (for example: canned fruit, bottled canned food, jam, fruit puree, etc.), fish, meat and their processed foods (for example: Ham, sausage, etc.), bread and noodles (e.g. udon noodles, soba noodles, instant noodles, pasta, macaroni, etc.), fruit juices, various beverages, cookies, syrup, dairy products (e.g. butter, Cheese, etc.), edible vegetable oil, margarine, vegetable protein, steamed food, frozen food, various condiments (for example: soybean paste, soy sauce, sauce, etc.) Prepare.

In the food composition of the present invention, the preferred content of the above-mentioned Polygonatum falciparum or Polygonatum angustifolia extract may include 0.001 to 99.999% by weight of the food composition of the present invention, but is not limited thereto.

In addition, in order to use the Polygonatum falciparum or Polygonatum angustifolia extract of the present invention as a food additive, it can be prepared and used in the form of powder or concentrated liquid.

In addition, the present invention relates to preparations for the prevention and treatment of one or more diseases selected from the group consisting of obesity, obesity complications or metabolic syndrome as Polygonatum falcatum or Polygonatum falcatum ( Polygonatum sibiricum) new application of Polygonatum sibiricum plant extract, also relates to the prevention and treatment of one or more diseases selected in the group consisting of obesity, obesity complications or metabolic syndrome, the method is characterized in that: An effective dose of Polygonatum plant extract as Polygonatum falcatum or Polygonatum sibiricum is administered to a subject in need thereof.

In the present invention, the so-called "effective dose" refers to the amount of the composition or preparation of the present invention that achieves drug delivery or prevents and treats obesity, obesity complications, or metabolic syndrome in the individual as the administration target. Quantity, the above-mentioned "subject" may be an animal, preferably a mammal, especially an animal including a human, or may be a cell, tissue, organ, etc. derived from an animal. The aforementioned individual may be a patient in need of treatment.

technical effect

In summary, the present invention relates to a new application of Polygonatum falciparum or Polygonatum angustifolia extract, which can maintain a high level of SIRT 1, reduce body weight, abdominal fat and glucose tolerance, It can be effectively used for the prevention and treatment of obesity, obesity complications or metabolic syndrome.

Description of drawings

Figure 1A is the result of using Western blot (Western blot) to determine the changes in SIRT1 protein expression after treating HEK 293 cell lines with ethyl acetate extracts belonging to the natural medicinal material Polygonatum (Polygonatum), and Figure 1B is in a larger range The results of measuring the expression of SIRT1 protein under the concentrations of Polygonatum angustifolia and Polygonatum angustifolia (C: negative control group; ID1216: ethyl acetate extract of Polygonatum angustifolia; ID1215: ethyl acetate extract of Polygonatum angustifolia; ID1214: ethyl acetate of Polygonatum angustifolia ester extract; ID1213: Polygonatum ethyl acetate extract).

Fig. 2 is the western blot result of measuring whether SIRT1 expression increases in each tissue of mice administered with Polygonatum sinica ethyl acetate extract and Polygonatum angustifolia ethyl acetate extract, and the expression of SIRT1 is determined in the order of liver, fat and muscle tissue ( Vehicle: negative control group).

Fig. 3 is the result of testing the anti-obesity effect of the composition of the present invention in an obese animal model, wherein the body weight of the mice was measured at different times. The value is the average standard deviation value of 9~10 mice, * means p<0.05, ** means p<0.01 means it is significant when compared with high-fat diet (□: normal diet; ■: high-fat diet; ▲ : high-fat feed + sibutramine (100mg/kg feed); ●: high-fat feed + ID1216 (5000mg/kg feed); ◆: high-fat feed + 1215 (5000mg/kg feed)).

Fig. 4 is a graph measuring liver and adipose tissue weights as a result of testing the anti-obesity effect of the composition of the present invention in an obese animal model. The value is the average standard deviation value of 9-10 mice, * means p<0.05, ** means p<0.01 means it is significant when compared with high-fat diet (□: normal diet; ■: high-fat diet; ▲ : High-fat feed + sibutramine (100mg/kg feed) (ND: normal feed group; HF: high-fat feed group; Sibutramine: high-fat feed + sibutramine (100mg/kg feed); ID1216: high-fat Feed + Polygonatum angustifolia ethyl acetate extract (5000mg/kg feed); ID1215: high-fat feed + Polygonatum ethyl acetate extract (5000mg/kg feed)).

Fig. 5 is the result of measuring the blood lipid concentration in an animal model of fattening. Fig. 5 A is the accompanying drawing of comparing blood cholesterol with high-fat diet group, Fig. 5 B is the accompanying drawing of comparing blood neutral fat with high-fat diet group, Fig. 5 C is the accompanying drawing of comparing blood free fatty acid concentration with high-fat diet group (ND : normal feed group; HF: high-fat feed group; Sibutramine: high-fat feed+sibutramine (100mg/kg feed); ID1216: high-fat feed+Pygonatum angustifolia ethyl acetate extract (5000mg/kg feed); ID1215: High-fat feed + Polygonatum ethyl acetate extract (5000mg/kg feed)).

Figure 6 shows the results of the changes in SIRT1 protein expression by Western blot after treating HEK 293 cell lines with the ethanol extracts and ethyl acetate extracts of Polygonatum sinensis and Polygonatum angustifolia respectively (C: negative control group ; ID1216: Polygonatum angustifolia ethyl acetate extract; ID1215: Polygonatum angustifolia ethyl acetate extract; ID1216B: Polygonatum angustifolia 80% ethanol extract; ID1215B: Polygonatum angustifolia 80% ethanol extract).

Fig. 7 is the result of testing the anti-obesity effect of the composition of the present invention in an animal model of fattening, wherein the body weight of the mice was measured at different times. The value is the average standard deviation value of 8 mice, * stands for p<0.05, ** stands for p<0.01, which means it is significant when compared with high-fat diet (□: normal diet; ■: high-fat diet; ◆: high-fat diet Fat feed + ID1215B (250 mg/kg); ▲: high fat feed + ID1215B (500 mg/kg); ●: high fat feed + ID1215B (750 mg/kg)).

Fig. 8 is a graph of liver and adipose tissue weights measured as a result of testing the anti-obesity effect of the composition of the present invention in an animal model of obesity. The value is the average standard deviation value of 8 mice, * represents p<0.05, ** represents p<0.01 and has significant significance when compared with high-fat diet (ND: normal diet group; HF: high-fat diet group; 250mg /kg: high-fat feed + ID1215B-250mg/kg; 500mg/kg: high-fat feed + ID1215B-500mg/kg; 750mg/kg: high-fat feed + ID1215B-750mg/kg).

Fig. 9 is the result of the cold test (Cold test) related to the anti-obesity effect of the composition of the present invention in an animal model of fattening. The value is the average standard deviation value of 8 mice, * stands for p<0.05, ** stands for p<0.01, which means it is significant when compared with high-fat diet (■: high-fat diet; ◆: high-fat diet+ID1215B( 250mg/kg); ▲: high-fat feed + ID1215B (500mg/kg); ●: high-fat feed + ID1215B (750mg/kg)).

Fig. 10 is the result of testing the effects related to metabolic syndrome in the fattening animal model. Fig. 10A is the result of measuring the blood glucose concentration after oral administration of glucose. The value is the average standard deviation value of 8 mice, * means p<0.05 means it has significant significance when compared with high-fat diet (□: normal diet; ■: high-fat diet; ◆: high-fat diet + ID1215B (250mg/ kg); ▲: high-fat feed + ID1215B (500 mg/kg); ●: high-fat feed + ID1215B (750 mg/kg)). Figure 10B compares the area under the curve (AUC, Area under curves) of the obese diet group and the ID1215B administration group after 8 weeks.

Fig. 11 is the result of measuring the blood lipid concentration in an animal model of fattening. Fig. 11 A is the accompanying drawing of comparing blood cholesterol with high-fat diet group, Fig. 11 B is the accompanying drawing of comparing blood neutral fat with high-fat diet group, Fig. 11 C is the accompanying drawing of comparing blood free fatty acid concentration with high-fat diet group (ND : normal feed group; HF: high-fat feed group; 250mg/kg: high-fat feed + ID1215B-250mg/kg; 500mg/kg: high-fat feed + ID1215B-500mg/kg; 750mg/kg: high-fat feed + ID1215B- 750mg/kg).

Fig. 12 is a diagram comparing the differences of fat and liver cells by observing the liver and adipose tissue after 8 weeks with an optical microscope in an obese animal model. Figure 12A is a drawing showing the difference in the size of adipocytes, and Figure 12B is a drawing showing the state of liver cells and the degree of fat vacuoles (ND: normal feed group; HF: high-fat feed group; 250mg/kg: high-fat feed+ID1215B -250mg/kg; 500mg/kg: high-fat feed + ID1215B-500mg/kg; 750mg/kg: high-fat feed + ID1215B-750mg/kg).

Detailed ways

The present invention will be described in detail below based on the examples.

However, the following examples are just examples of the present invention, and the content of the present invention is not limited to the following examples.

<Example 1>

The extract was found to enhance the potency of SIRT1 expression

<1-1>Comparison of enhanced expression of SIRT1 (in vitro)

In order to screen the extract with the highest SIRT1 activity, Polygonatum sibiricum (Polygonatum sibiricum: ID1216), Polygonatum falcatum (Polygonatum falcatum: ID1215), Polygonatum stenophyllum (Polygonatum stenophyllum: ID1214) and Four kinds of ethyl acetate extracts including Polygonatum lasianthum: ID1213.

The extraction method of ethyl acetate extract is that after each sample 10g sample is pulverized, impregnate with 100% methanol of 30ml, extract repeatedly 3 times at normal temperature, each time 24 hours, utilize filtering device to filter extraction solution, utilize reducing Press the device to remove methanol, and obtain no methanol extract. After adding 20 ml each of ethyl acetate and water to the methanol extract obtained by the above-mentioned procedure for extraction, the supernatant was concentrated to obtain an ethyl acetate extract.

Each sample of the ethyl acetate extract was washed twice with ethanol, concentrated under reduced pressure after removing the residual solvent, dissolved in DMSO at a predetermined concentration, and added to serum-free Dulbecco's modified Eagle medium (DMEM) at a ratio of 0.5% (v/v). ), the proteins obtained after culturing HEK 293 cells in this medium for 16-20 hours were subjected to electrophoresis in 8% SDS-PAGE colloid, and then transferred to PVDF membrane (membrane) for support. Technology, the United States) for the detection and retrieval system of immunoblotting (immunoblotting). As a control group, a drug-free DMSO-treated group was used to screen for a drug that increases the expression of SIRT1 compared to the control group.

The results are shown in FIG. 1A . It was found that the above four kinds of ethyl acetate extracts all had the activity of enhancing the expression of SIRT1, and the extract of Polygonatum sinensis (ID1215) had the highest activity. In addition, as shown in FIG. 1B , the extract of Polygonatum sinensis (ID1215) also exhibited the effect of enhancing the expression of SIRT1 at a concentration more than 8 times lower than that of Polygonatum angustifolia (ID1216).

<Example 2>

In vivo SIRT1 expression assay for ID1215 and ID1216

In order to confirm whether ID1215 and ID1216 enhance the expression of SIRT1 in vivo, C57BL6 mice were used as objects, and the expression patterns of SIRT1 in various organs were found.

All animal surgeries were performed in accordance with the guidelines of the Animal Ethics Committee of Nitto Pharmaceutical. Eight-week-old C57BL/6 male mice were purchased from Dongfang Biological Company. Keep the breeding room at a temperature of 23°C, a humidity of 50±10%, and a cycle of 12 hours (daylight 08:00-20:00) in the brightness, and start the experiment after adapting to the environment within 1 week. To help absorption, give ID1215 and ID1216 to fasting rats at a dose of 500mg/kg body weight (=500mpk). Five hours after the administration, the mice were killed, and the liver, fat, and muscle were removed. A portion of the excised tissue was snap-frozen in liquid nitrogen for RNA extraction, and then stored at -70°C until use. The rest of the extracted tissues were put into Homogenization buffer (10mM Tris, pH 7.4, 150mM NaCl, 1mM EDTA, 10% glycerol, 0.1% After Triton X-100), the protein was quantitatively determined by BCA quantitative method. To confirm the expression of SIRT1, for other tissues except muscle, 60 μg of protein (100 μg for muscle) was separated in 8% SDS-PAGE gel, supported by PVDF membrane, and blocked with 5% skim milk for 10 Minutes, using anti-Sirt1 antibody to implement Western blot (Western blot).

The results are shown in Figure 2, ID1216 and ID1215 showed similar patterns in both fat and muscle, and increased the expression of SIRT1 protein.

<Example 3>

Anti-obesity efficacy test of ID1215 and ID1216

Both ID1215 and ID1216 are expected to exhibit anti-obesity effects through SIRT1 expression assays. In order to compare the anti-obesity effects of ID1215 and ID1216, which have higher SIRT1 activity enhancing potency in vitro, a DIO model test was carried out.

<3-1>Using high-fat diet to make obesity model of fattening mice

In the experiment, ID1215 and ID1216 were added to a high-fat diet containing 40% fat, and the diet was fed to 8-week-old C57BL6 mice for 12 weeks.

In the high-fat diet, the anti-obesity efficacy positive control group was mixed with 0.01% sibutramine, 0.5% each of ID1215 and ID1216, and kept in cold storage until use. The composition of the feed is shown in Table 1.

【Table 1】

ingredients g/kg Casein 120 DL-Methionine 1.8 Corn starch (Cornstarch) 90 Sucrose 300 Cellulose 30 Corn Oil 30 Salt Mix twenty one Vitamin Mix 6 Choline Bitartrate 1.2 Beef Tallow 400

Animal preparation was the same as in Example 2. Mice were fed a high-fat diet for 12 weeks ad libitum. The test groups were normal feed treatment group (ND) without butter, high-fat feed group (HF) without drug treatment, groups containing 5000 mg each of ID1215 and ID1216 per kg of high-fat feed (ID1215, ID1216), The group (sibutramine) containing 100 mg of sibutramine per kg of high-fat feed was tested in groups of 10 animals.

<3-2> Determination of body weight change

Body weight was measured once a week. After the experiment, mice in all groups recovered plasma, dissected, and measured the weight of liver and abdominal fat. Part of the liver tissue and adipose tissue were stained and observed.

The results are shown in Figure 3. Compared with the high-fat diet group, the body weight of the obese feed administration group added with ID1216 and ID1215 decreased by 8.6% and 25.9% after 12 weeks. Although the drug group had an obesity suppressing effect at the initial stage, the effect disappeared after 8 weeks. In addition, as shown in Table 2 and Figure 4, when the drug-administered group was autopsyed after 12 weeks, compared with the high-fat diet group, the amount of abdominal fat tissue in the ID1216 group decreased by 3.2%, and that in the ID1215-administered group decreased by 41.9%. The reduction in the sibutramine-administered group was 3.2%. In terms of liver mass, the ID1216 group decreased by 6.2% compared to the fat-fed group, and the ID1215 group decreased by 31.2%. In the sibutramine-administered group, the liver weight did not change. As a result of the histological analysis of the liver tissue, it was found that the extensive and fine distribution of fat in the liver tissue of the high-fat diet group became local distribution in the ID1215 administration group, and the relief was mild. (results not shown)

【Table 2】

%Proportion liver Fat ND 68.8 32.3 HF 100.00 100.00 Sibutramine 100.00 96.8 ID1216 93.8 96.8 ID1215 68.8 58.1

<3-3> blood test

After the experiment, blood was collected from the mice of each group, and the plasma was separated. Cholesterol was analyzed with an automatic dry chemical analyzer (A25analyzer, Biosystems), neutral fat was analyzed using Triglyceride assaykit (Cayman), and free fatty acids were measured using NEFA (Wako) according to the manufacturer's instructions.

As a result, as shown in Figure 5 and Table 3, it was found that as an index related to metabolic syndrome, the amount of total cholesterol in the blood was reduced by 10.6% in the ID1216-administered group and 10.6% in the ID1215-administered group compared with the high-fat diet group. 27.8%, in terms of neutral fat and free fatty acid, the ID1216 administration group decreased by 14.9% and 15.4%, respectively, and the ID1215 administration group decreased by 27.0% and 38.2%. ID1216 is expected to have a weak weight gain inhibitory effect and reduction in fat and liver tissue volume, but on the contrary, the improvement effect on metabolic syndrome-related indicators is relatively high. Compared with ID1216, ID1215 has an improvement effect on all metabolic syndrome diseases such as obesity higher.

【table 3】

%Proportion cholesterol neutral fat free fatty acids ND 52.6 55.7 53.2 HF 100.00 100.00 100.00 Sibutramine 112.2 89.7 96.4 ID1216 89.4 83.1 84.6 ID1215 72.2 73.0 61.8

Based on the results of the anti-obesity and metabolic syndrome-related efficacy tests of ID1215 and ID1216 in the above examples, it can be seen that these compositions are non-toxic when administered orally for a long time at a dosage of 500 mg/kg, which is different from Western medicines currently on the market as obesity therapeutic agents. Compared with butramine, it not only shows the same anti-obesity effect, but also can improve various indicators related to obesity and metabolic syndrome.

<Example 4>

Establish optimal extraction conditions for extracts

In the case of using an organic solvent such as ethyl acetate, when it is to be used for food or the human body, the separation and purification process is complicated, and it often occurs that it cannot be used due to the residual organic solvent. Therefore, an extraction method using edible ethanol (alcohol) has been established. Simultaneously, for the purpose of increasing the active ingredient content of the present invention in the extract, increasing the amount of extraction, easy to realize process and reduce production cost during mass production, the best extraction condition test was carried out.

The method for obtaining the ethyl acetate extract is the same as that of Example 1. After pulverizing 10g of the sample, impregnate it with 30ml of 100% methanol, repeat the extraction at room temperature for 3 times, each time for 24 hours, filter the extraction solution with a filter device, remove methanol with a decompression device, and collect the methanol extract. After adding 20 ml each of ethyl acetate and water to the methanol extract obtained through the above process for extraction, the supernatant was concentrated to obtain the ethyl acetate extract.

Meanwhile, in order to simplify the extraction process, 80% ethanol was used and the extraction was performed as follows. Add 30ml of 80% ethanol to the pulverized 10g sample for immersion, repeat the extraction 3 times for 24 hours each time, filter the extraction solution with a filter device, remove the solvent with a decompression device, and obtain 80% ethanol extract. The 80% ethanol extract showed an extraction rate of 17% relative to the weight of the sample, which was 85 times higher than the extraction rate of 0.2% of the ethyl acetate extract.

<Example 5>

SIRT1 expression enhancement test of ethanol extracts of ID1215 and ID1216

Each extract extracted in the above-mentioned Example 4 was dissolved in DMSO at a predetermined concentration, and the method of Example 1 was used to test whether the activity of SIRT1 was improved.

In order to screen the extracts of the solvents that most enhance the activity of SIRT1, the 80% ethanol extracts and ethyl acetate extracts of Polygonatum falcatum and Polygonatum sibiricum of the present invention collected from various places in Korea were compared. thing. As in Example 1, the extract was used to treat HEK293 cells at different concentrations, and Western blot was used to verify the increased expression of SIRT1.

The results are shown in Figure 6, Polygonatum angustifolia 80% ethanol extract (ID1216B) and Polygonatum syringae 80% ethanol extract (ID1215B) showed a similarity with Polygonatum angustifolia ethyl acetate extract (ID1216) and Polygonatum syringae ethyl acetate extraction. SIRT1 expression-enhancing potency similar to the drug (ID1215).

For the 80% ethanol extract (ID1215B) of Rhizoma Polygonatum (ID1215B), which not only has advantages in the safety and economical aspects of the extract, but also has a high effect of enhancing the expression of SIRT1 in cells, it was administered to mice at 250, 500, and 750 mg/kg. Drug, verified anti-obesity efficacy.

<Example 6>

Anti-Obesity Efficacy Test of ID1215B

<6-1>Using high-fat diet to make mouse obesity model

The test is to feed 8-week-old C57BL6 mice with 40% fat-containing feed, and once a day orally, according to the dose of 250, 500, and 750 mg/kg, and feed ID1215B dissolved in PBS to determine Changes in body weight during 8 weeks. After 8 weeks, compare the changes of various obesity and related indicators with the normal diet and obese diet mouse groups.

The test groups were the normal feed treatment group (ND) without butter, the high-fat feed group (HF) without drug treatment, and the group fed ID1215B 250 mg/kg once a day while feeding high-fat feed (ID1215B- 250mg/kg), the group fed with high-fat feed and ID1215B 500mg/kg once a day (ID1215B-500mg/kg), the group fed with high-fat feed and ID1215B 750mg/kg once a day (ID1215B- 750mg/kg), every group of 8 was tested. In order to obtain the same test results as the ID1215B administration group, ND and HF were fed with PBS once a day.

<6-2> Determination of body weight change

Body weight was measured once a week. After the experiment, mice in all groups recovered plasma, dissected, and measured the weight of liver and abdominal fat. A part of liver tissue and adipose tissue were histologically stained and observed.

The results are shown in Figure 7. Compared with the high-fat diet group, the body weight of the ID1215B administration group decreased by 17.0%, 15.4%, and 17.0% in the 250, 500, and 750 mg/kg administration groups after 8 weeks. In addition, as shown in Table 4, Figure 8 and Figure 12, when the drug-administered group was autopsyed after 8 weeks, compared with the high-fat diet group, in all ID1215B-administered groups, the amount of abdominal adipose tissue was reduced by 10%. As above, the size of adipocytes also decreased (see FIG. 12A ). In the 250, 500, and 750 mg/kg administration groups, compared with the high-fat diet group, the mass of the liver decreased by 18.6%, 14.0%, and 24.4%, respectively. As a result of histochemical analysis of the liver tissue, it was found that the fat distributed widely and finely in the liver tissue of the high-fat diet group became localized in the ID1215B-administered group, and the fat was alleviated to a mild degree (see FIG. 12B ).

【Table 4】

<6-3> Low temperature test (cold test)

In order to understand the cause of body weight loss, a low temperature test (cold test) was carried out. The mice were placed in a low-temperature space at 4°C, and the rectal temperature was measured and recorded every 1-2 hours within 8 hours, and compared with the basal body temperature.

The results are shown in Figure 9. The ID1215B administration group overcame the drop in body temperature in the high-fat feed group to a considerable extent. Therefore, it can be seen that the body weight gain inhibition effect due to ID1215B administration is due to the increased heat dissipation caused by the active metabolism in the body. result.

<6-4> Glucose tolerance measurement for insulin resistance

In order to measure the glucose tolerance caused by insulin resistance, blood was taken from the tail of mice fasted for more than 16 hours, and the blood sugar was measured (0 points), 10, 20, 30, 60, 120 minutes after the injection of glucose at 2 g/kg Blood was drawn, blood sugar was measured and recorded.

The results are shown in Figure 10, the area under the curve (AUC, Area under curves) of 250, 500, 750mg/kg dose ID1215B administration groups were 14236*, 8387*, 7789* respectively, compared with the high-fat diet group, decreased respectively 31.6%, 59.7%, 62.6%, improved glucose tolerance (* represents p<0.05).

<6-5> blood test

After the experiment, blood was collected from the mice of each group, and plasma was separated. Toxicity-related indicators and cholesterol were analyzed using an automatic dry chemical analyzer (A25analyzer, Biosystems). Neutral fat and free fatty acids were measured using Triglyceride assay kit (Cayman) and NEFA (Wako), respectively, according to the manufacturer's guidelines.

The results are shown in Table 5 and Figure 11. As an index related to metabolic syndrome, there is no valuable difference in blood cholesterol, but in the ID1215B administration group, the neutral fat was reduced by 30.1%, 42.5%, and 42.5%, respectively. and 47.2%, showing concentration dependence. Free fatty acids were also reduced by 7.1%, 7.1%, and 14.3%, respectively. Therefore, it is expected that ID1215B not only suppresses weight gain but also has the effect of improving multiple metabolic syndrome diseases.

【table 5】

In addition, as shown in Table 6, the ID1215B administration group reduced the hepatotoxicity-related indicators (ALT, AST, etc.) shown in the obese group to a degree similar to that of the normal feed group, and the cardiotoxicity-related indicators ( Sarcosine, BUN, etc.) compared with the normal feed group, did not show significant changes.

【Table 6】

<6-6> Light Microscopic Observation of Liver and Adipose Tissue

After the animal experiment, in order to confirm the changes in the liver and adipose tissue, H&E (hematoxylin and eosin) staining was performed for light microscope observation.

The extracted liver and adipose tissue were cut into a predetermined size, fixed in 10% formalin according to the usual method, washed with water, embedded in paraffin, and made into blocks. The resulting blocks were sliced into 4-m thick sections, and stained with hematoxylin and eosin to observe general changes.

All concentrations of ID1215B administration group did not have the same yellow-brown discoloration as the high-fat feed group, but showed a bright red color similar to that of the normal feeding group, and the scope and degree of vacuolar degeneration were significantly reduced. From the results of fat tissue analysis, it was confirmed that the size of adipocytes was smaller in all doses of the ID1215B-administered group than in the high-fat diet group (see FIG. 12 ).

<Example 7>

Single and repeated dose toxicity test

In order to confirm whether ID1215B induces toxicity when administered orally, single-dose toxicity and 4-week repeated-dose toxicity tests were carried out.

For single toxicity, 6 male ICR mice aged 6 weeks were used as a group. After a single oral administration of ID1215B at 1,000-5,000 mg/kg body weight, observe whether they survived during 2 weeks. After the experimental animals were euthanized, passed Necropsy was performed to observe abnormal organs. In the groups administered with ID1215B at all concentrations, no animals died, no abnormality was found in organs, and it was judged as non-toxic (results not shown).

Toxicity of repeated administration: 6 male ICR mice aged 6 weeks were used as a group. ID1215B was orally administered at 1,000~3,000 mg/kg body weight, once a day, and repeated administration for 28 days. At the same time, observe the weight change and general symptoms And whether they survived, after the experimental animals were euthanized, the abnormal organs were observed through autopsy. In all concentrations of ID1215B administration groups, there were no dead animals, and no abnormalities were found in organs. As shown in Table 7, in the indicators related to liver toxicity such as ALT and AST, and the indicators related to cardiotoxicity such as sarcosine and BUN, there were also no abnormalities. There were no significant changes.

ID1215 also confirmed single (1,000~3,000mg/kg body weight) and 7-day repeated administration toxicity (500~1,500mg/kg body weight) by the above method. There was no vehicle and significant difference in blood biochemical indicators related to toxicity and cardiotoxicity (results not shown).

【Table 7】

Based on the results of obesity and metabolic syndrome-related efficacy and toxicity tests of ID1215B in the above-mentioned examples, it can be known that this composition is not only non-toxic when it is given at a high dose of 5000 mg/kg for a single administration and when it is repeatedly administered at a dose of 3000 mg/kg. 750mg/kg is the maximum dose when administered orally for a long time. It has no toxicity, has anti-obesity effect, and improves various indicators related to metabolic syndrome.

【Possibility of Industrial Utilization】

The present invention relates to a new application of Polygonatum falciparum or Polygonatum angustifolia extract as an active ingredient, which is used to prepare pharmaceutical or food compositions for preventing and treating obesity, obesity complications or metabolic syndrome, A preparation for prevention and treatment of obesity, obesity complications, or metabolic syndrome. , the above-mentioned Polygonatum falciparum or Polygonatum angustifolia extract maintains a high level of SIRT1 protein in cells, and has the effect of reducing body weight, reducing abdominal fat and glucose tolerance, so it can be used as a preventive and therapeutic agent for obesity, obesity complications or metabolic syndrome. Active ingredient of therapeutic pharmaceutical composition or food composition.

Claims (5)

1. a prevention and medicine for treatment compositions that contains more than one diseases of in the group that constitutes by fat, obesity complication and metabolic syndrome, selecting of reaping hook Rhizoma Polygonati extract or narrow leaf Rhizoma Polygonati extract.

2. food compositions is used in a prevention and an improvement that contains more than one diseases of in the group that is made up of obesity, obesity complication and metabolic syndrome, selecting of reaping hook Rhizoma Polygonati extract or narrow leaf Rhizoma Polygonati extract.

3. compositions according to claim 1 and 2 is characterized in that:

Said extract is more than one the solvent extractable matter of in the group that is made up of water, ethanol, ethanol, methanol, propanol, isopropyl alcohol, butanols, acetone, ether, chloroform, ethyl acetate, dichloromethane, hexane, cyclohexane extraction, petroleum ether, diethyl ether, benzene, selecting.

4. prevention and the reaping hook Rhizoma Polygonati extract of therapeutic preparation or purposes of narrow leaf Rhizoma Polygonati extract that is used for being prepared in more than one diseases that the group that is made up of fat, obesity complication and metabolic syndrome selects.

5. the prevention and the Therapeutic Method of more than one diseases of in the group that is made up of fat, obesity complication and metabolic syndrome, selecting is characterized in that: reaping hook Rhizoma Polygonati extract or narrow leaf Rhizoma Polygonati extract with effective dose to its individual administration of needs.

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