Composition for preventing, alleviating, or treating fatty liver disease, comprising gintonin derived from red ginseng meal as active ingredient

Abstract

The present invention relates to a composition for preventing, alleviating, or treating fatty liver, comprising gintonin derived from red ginseng meal as an active ingredient. The present invention uses gintonin isolated from by-products of red ginseng, which is widely used as a health functional food, and thus has almost no side effects, is safe, and has the advantage of lowering unit cost to enable long-term administration. In addition, anti-obesity, metabolic rate increase, and liver fat accumulation inhibitory effects thereof were identified through specific experiments, and thus the present invention is expected to be effectively used as a pharmaceutical, food or the like for preventing, alleviating, or treating fatty liver disease.

Description

Composition for preventing, improving, or treating fatty liver disease, containing gintonin derived from red ginseng extract as an active ingredient

[0001] The present invention relates to a composition for preventing, improving, or treating fatty liver disease, including ginseng extract-derived ginseng as an active ingredient.

[0002] Obesity refers to a state in which an excessive amount of body fat accumulates in the body. In 1996, the World Health Organization defined obesity as a disease requiring long-term treatment. Since then, obesity has been recognized as one of the important diseases that modern mankind must overcome. According to the World Health Organization, the number of obese people worldwide will reach 1.038 billion in 2022, which means that one in eight people worldwide is obese. It is predicted that more than half of adults worldwide will be overweight or obese by 2030. In Korea, the adult obesity rate has steadily increased over the past 10 years, and according to the 2020 National Health and Nutrition Examination Survey published by the Korea Disease Control and Prevention Agency, the adult obesity rate was 48% for men and 27.7% for women, a 12.9% increase for men compared to 2011. As the degree of obesity increases, the risk of disease also increases. In the case of severe obesity with a body mass index (BMI) of 30 or higher, which is one of the criteria for diagnosing obesity, it is also called morbid obesity to recognize obesity itself as a disease. Morbid obesity causes various complications, and its contribution has been announced to be 75% for hypertension, 33% for cancer, 44% for diabetes, and 23% for ischemic heart disease. In addition, morbid obesity affects respiratory diseases such as non-alcoholic fatty liver disease, pulmonary dysfunction, and obstructive sleep apnea, and diseases such as gastroesophageal reflux disease, and is also known to be related to the development of various cancers such as breast cancer and endometrial cancer.

[0003] Fatty liver disease (FADL) occurs when fat deposits exceed 5% of the liver's weight, resulting in the accumulation of triglycerides in liver cells. With the rise in obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) in Korea is rapidly increasing, estimated at approximately 30%. Fatty liver disease can progress to steatohepatitis and, not infrequently, cirrhosis or liver cancer, necessitating regular checkups and vigilant attention. The most important treatment for NAFLD is to address obesity, its primary cause, and to suppress fat accumulation in the liver. Existing obesity treatments include appetite suppressants, fat absorption inhibitors, and glucagon-like peptide-1 (GLP-1). However, these drugs have shown minimal efficacy in treating fatty liver disease or have been reported to have significant side effects. Therefore, the development of safe and economical treatments for fatty liver disease that can be used long-term and minimize side effects is crucial.

[0004] Meanwhile, ginseng is a medicinal plant of the Araliaceae family, and depending on the processing method, there are unprocessed fresh ginseng, white ginseng made by drying fresh ginseng, red ginseng made by steaming and drying fresh ginseng, and black ginseng made by steaming and drying fresh ginseng four or more times. When red ginseng is extracted with water or alcohol to produce a concentrated extract product, red ginseng marc is produced. Ginseng and red ginseng are known to contain various types of ginsenosides as effective ingredients, and are widely used as health foods due to their various efficacies, but their high price limits their economic use. Through prior research, the present inventors isolated gintonin, a new physiologically active substance from ginseng (Domestic Patent No. 10-0973202), and identified that the physiologically active functional component of ginseng is lysophosphatidic acid (LPA), and isolated gintonin by extracting red ginseng marc, a by-product of red ginseng, with ethanol (Domestic Patent Publication No. 10-2024-0028016).

[0005] Accordingly, the inventors of the present invention completed the present invention by further confirming through this study that ginseng extract contained in red ginseng extract has an effect of suppressing obesity and liver fat accumulation.

[0006] The technical problem to be achieved by the present invention is to provide a composition for preventing, improving, or treating fatty liver disease, which contains gintonin derived from red ginseng extract as an active ingredient.

[0007]

[0008] However, the technical problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

[0009] In order to solve the above problem, the present invention provides a pharmaceutical composition for preventing or treating fatty liver disease, which comprises gintonin derived from red ginseng extract as an active ingredient.

[0010] In addition, the present invention provides a food composition for preventing or improving fatty liver disease, which contains gintonin derived from red ginseng extract as an active ingredient.

[0011] As one embodiment of the present invention, the gintonin may be isolated from a red ginseng extract.

[0012] As another embodiment of the present invention, the red ginseng extract may be extracted with at least one solvent selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof.

[0013] As another embodiment of the present invention, the red ginseng extract may be an ethanol extract.

[0014] As another embodiment of the present invention, the gintonin may include lysophosphatidic acid (LPA) as a functional ingredient.

[0015] In another embodiment of the present invention, the fatty liver disease may be non-alcoholic fatty liver disease.

[0016] In addition, the present invention provides a method for preventing or treating fatty liver disease, comprising a step of administering to a subject a composition containing ginseng extract-derived ginseng.

[0017] In one embodiment of the present invention, the subject may be a mammal that is likely to develop fatty liver disease due to environmental or genetic predisposition, exhibits fatty liver symptoms or similar symptoms, or has developed fatty liver disease.

[0018] In another embodiment of the present invention, the administration may be oral administration.

[0019] In addition, the present invention provides a use of ginseng extract-derived ginseng for the preparation of an agent for the prevention or treatment of fatty liver disease.

[0020] The present invention relates to a composition for preventing, improving, or treating fatty liver disease using gintonin derived from red ginseng extract. Since it utilizes gintonin isolated from a byproduct of red ginseng, which is widely used as a health functional food, it has the advantage of being safe with almost no side effects, can be inexpensive, and can be taken for a long period of time. In addition, through specific experiments, its anti-obesity, metabolic increase, and liver fat accumulation inhibitory effects were confirmed, and it is expected to be usefully used as a pharmaceutical or food for preventing, improving, or treating fatty liver disease.

[0021] Figure 1 is a diagram illustrating the process of manufacturing red ginseng extract and separating ginseng.

[0022] Figure 2 shows the weight loss effect through oral administration of red ginseng extract. Figure 2a shows the results of measuring body weight every week in a normal control group (CD+Veh), an obesity-induced control group fed a high-fat diet (HFD+Veh), an obesity-induced group fed a low-concentration extract (HFD+G50), and an obesity-induced group fed a high-concentration extract (HFD+G200), and Figure 2b shows the results of measuring body weight in the last week of extract administration in each of the above mouse groups.

[0023] Figure 3 shows the effect of increasing metabolic amount through oral administration of red ginseng extract. Figure 3a shows the results of measuring metabolic amount while conducting a metabolic cage experiment in each mouse group, Figure 3b shows the results of measuring metabolic amount in each mouse group in the light and night cycle, and Figure 3c shows the results of analyzing the activity of each mouse group in the metabolic cage in the light and night cycle.

[0024] Figure 4 shows the results of measuring the mRNA levels of genes related to brown fat (BAT) after oral administration of red ginseng extract in each mouse group.

[0025] Figure 5 shows the effect of inhibiting liver fat accumulation through oral administration of red ginseng extract. Figure 5a shows the results of measuring the liver weight of each mouse group, Figures 5b and 5c show the results of measuring positive immunity after staining the liver tissue of each mouse group with H&E and Oil red O, respectively, and Figure 5d shows photographs of the liver tissue stained with H&E and Oil red O in each mouse group.

[0026] The present inventors completed the present invention by confirming that gintonin derived from red ginseng extract has anti-obesity and fatty liver treatment effects in a high-fat diet-induced obesity animal model.

[0027] Specifically, the inventors of the present invention prepared a red ginseng extract containing ginseng root according to the process illustrated in Fig. 1 and administered it orally three times a week for 25 weeks to a high-fat diet-induced obesity mouse model to investigate its anti-obesity effect. As a result, a significant weight loss effect was confirmed in the obesity-induced group (HFD+G200) administered a high concentration of the extract compared to the obese control group (HFD+Veh) that was not administered the extract.

[0028] In addition, the inventors of the present invention analyzed the metabolic changes caused by oral administration of red ginseng extract by conducting a metabolic cage experiment 12 to 15 weeks after oral administration of the extract. As a result, it was found that the metabolic amount significantly increased in the obesity-induced group (HFD+G200) fed a high concentration of red ginseng extract compared to the obese control group, and a tendency for higher activity was confirmed. Furthermore, as a result of analyzing the mRNA expression levels of brown fat-related genes in each mouse group, it was confirmed that the expression of UCP1, a gene involved in thermogenesis and energy homeostasis, was significantly increased in the obesity-induced group fed a high concentration of red ginseng extract.

[0029] In addition, based on the above results, to investigate the effect of red ginseng extract on fatty liver, the livers of each group of mice were extracted, their weights were measured, and histological analysis was performed. As a result, it was shown that the liver weight was reduced in a concentration-dependent manner in the obesity-induced group fed red ginseng extract compared to the obesity-induced control group. Furthermore, the H&E staining results showing the liver tissue structure showed that the stained tissue immunity increased in the group fed the extract, and the Oil red O staining results showing the proportion of fat accumulated in the liver tissue showed that the area of ​​lipid droplets in the liver tissue was reduced in a dose-dependent manner.

[0030] In summary, the above results indicate that red ginseng extract has anti-obesity, metabolic increase, and fatty liver treatment effects.

[0031] In addition, the inventors of the present invention isolated crude gintonin from red ginseng extract ethanol through a previous study (Korean Patent Publication No. 10-2024-0028016), and confirmed that the gintonin contains a large amount of lysophosphatidic acid (LPA), a physiologically active functional ingredient, and phosphatidylcholine, a precursor thereof.

[0032] Accordingly, the present invention provides a pharmaceutical composition for preventing or treating fatty liver disease, which contains gintonin derived from red ginseng extract as an active ingredient.

[0033] In the present invention, “gintonin” is a substance contained in red ginseng marc, and preferably can be separated from a red ginseng marc extract. The gintonin includes lysophosphatidic acid, which is a physiologically active functional ingredient, and may include phosphatidylcholine, which is a precursor thereof. The lysophosphatidic acid may be at least one selected from the group consisting of LPA C18:2, LPA C16:0, and LPA C18:1, but is not limited thereto. The phosphatidylcholine may be at least one selected from the group consisting of PC C16:0-18:2 and PC C18:0-18:2, but is not limited thereto.

[0034] The above gintonin may additionally include, but is not limited to, glucose, arabinose, galactose, xylose, and fucose.

[0035] Additionally, the gintonin may additionally include, but is not limited to, linoleic acid, palmitic acid, oleic acid, and stearic acid.

[0036] In the present invention, “red ginseng marc” refers to ginseng processed by heat and / or pressure, i.e., the residue remaining after extracting red ginseng with water or alcohol to make a red ginseng product, and may be obtained by drying red ginseng after extracting it with water or alcohol, but is not limited thereto.

[0037] The above red ginseng extract includes not only the crude red ginseng extract but also all forms obtained by further processing of the extract.

[0038] The above red ginseng extract may be red ginseng extract itself, a pulverized product thereof, or an extract obtained through an extraction process.

[0039] The above red ginseng extract can be extracted using a conventional solvent under conditions of conventional temperature and pressure according to a conventional method known in the art for extracting extracts from natural materials. For example, in the present invention, the red ginseng extract can be extracted using at least one solvent selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof, preferably using ethanol, and more preferably using 70% ethanol.

[0040] In addition, the method for extracting the extract from red ginseng extract can be by a conventional method known in the art, and non-limiting examples thereof include static extraction, hot water extraction, cold extraction, reflux extraction, ultrasonic extraction, etc. Preferably, it can be prepared by reflux extraction at 60°C to 100°C, more preferably at 80°C for 6 to 10 hours, and even more preferably for 8 hours.

[0041] The above-mentioned prepared extract can then be filtered, concentrated, or dried to remove the solvent. Filtration, concentration, and drying can all be performed. For example, filtration can be performed using filter paper or a vacuum filter, concentration can be performed using a vacuum concentrator, and drying can be performed using spray drying or freeze drying, but is not limited thereto.

[0042] In addition, the extract extracted with the above solvent can be further subjected to a fractionation process with a solvent selected from the group consisting of n-butanol, n-hexane, dimethyl chloride, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water, and mixtures thereof.

[0043] The term "prevention" in the present invention refers to any act of suppressing or delaying the symptoms of fatty liver disease by administering ginseng extract or fraction containing ginseng derived from red ginseng according to the present invention.

[0044] The term "treatment" in the present invention refers to any act in which the symptoms of fatty liver disease are improved or beneficially changed by administering red ginseng extract or fraction containing the red ginseng extract or fraction according to the present invention.

[0045] In the present invention, “fatty liver disease” refers to a condition in which fat accumulates in liver cells. In the case of a normal liver, the proportion of fat is less than 5%, but a condition in which more fat accumulates than this is called fatty liver. Fatty liver can be broadly classified into alcoholic fatty liver caused by excessive drinking and non-alcoholic fatty liver related to obesity, diabetes, hyperlipidemia, and drugs. In the present invention, fatty liver may include all fatty liver in which fat accumulates in the liver, and preferably may be non-alcoholic fatty liver whose main cause is obesity, but is not limited thereto.

[0046] The term "active ingredient" in the present invention means an ingredient that exhibits the desired activity alone or can exhibit the desired activity together with a carrier or the like that is inactive in itself.

[0047] The term "pharmaceutical composition" in the present invention refers to a composition manufactured for the purpose of preventing or treating a disease, and may be formulated and used in various forms according to each conventional method. For example, it may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, etc., and may be formulated and used in the form of topical preparations, suppositories, and sterile injectable solutions. Specifically, it may be formulated and used in a form suitable for eye drop administration, such as eye drops, creams, ointments, gels, or lotions.

[0048] The composition of the present invention may be prepared in the form of a pharmaceutical composition for preventing or treating fatty liver disease, which additionally includes an appropriate carrier, excipient, or diluent commonly used in the preparation of pharmaceutical compositions, and the carrier may include a non-naturally occurring carrier.

[0049] In the present invention, carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

[0050] When formulated, it is usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and these solid preparations are prepared by mixing the above-mentioned mulberry leaf extract and its fractions with at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, Tween 61, cacao butter, laurin, and glycerogelatin.

[0051] The pharmaceutical composition of the present invention can be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, etc., depending on the intended method, and the active ingredient of the pharmaceutical composition will vary depending on the age, sex, weight, pathological condition and its severity, administration route, or prescriber's judgment of the subject to be administered. Determination of the application amount based on these factors is within the level of those skilled in the art, and the daily administration dose thereof can be, for example, 0.1 mg / g / day to 100 mg / g / day, more specifically, 5 mg / g / day to 50 mg / g / day, and the administration frequency of the composition of the present invention is not particularly limited thereto, but can be administered once a day or administered several times in divided doses. The above dosage does not limit the scope of the present invention in any way.

[0052] In addition, the present invention provides a food composition for preventing or improving fatty liver disease, which comprises red ginseng marc-derived gintonin as an active ingredient. In addition, the red ginseng marc-derived gintonin can be added to food for the purpose of preventing or improving fatty liver disease. When used as a food additive, the substance can be added as is or used together with other foods or food ingredients, and can be used appropriately according to a conventional method. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing a food or beverage, the red ginseng marc-derived gintonin of the present invention is added in an amount of 15 wt% or less, preferably 10 wt% or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount can be below the above range, and since there is no problem in terms of safety, the active ingredient can also be used in an amount above the above range.

[0053] The term “improvement” in the present invention means any act of improving or beneficially changing the symptoms of fatty liver disease by administering the composition.

[0054] The food composition of the present invention may additionally include a food-related acceptable carrier.

[0055] There is no particular limitation on the types of foods to which the composition containing the red ginseng extract-derived gintonin of the present invention can be added, and examples thereof include various beverages, gum, tea, vitamin complexes, health supplements, etc. The food composition may contain other ingredients that do not interfere with the therapeutic effect of fatty liver disease, and the types thereof are not particularly limited. For example, as with conventional foods, various herbal extracts, food-related acceptable food additives, or natural carbohydrates may be contained as additional ingredients.

[0056] The above food additives are added in the manufacture of health functional foods of each formulation, and can be appropriately selected and used by those skilled in the art. For example, they include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc., but the types thereof are not limited by the above examples.

[0057] At this time, the content of red ginseng extract or fraction containing ginseng derived from red ginseng contained in the food is not particularly limited thereto, but may be included in an amount of 0.01 to 100 wt%, specifically 1 to 80 wt%, based on the total weight of the food composition.

[0058] If the food is a beverage, it may be included in a ratio of 1 to 30 g, specifically 3 to 20 g, based on 100 ml. In addition, the composition may include additional ingredients commonly used in food compositions to improve smell, taste, sight, etc. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, etc. In addition, it may include minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), etc. In addition, it may include amino acids such as lysine, tryptophan, cysteine, and valine. In addition, food additives such as preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), sterilizers (bleaching powder and high-purity bleaching powder, sodium hypochlorite, etc.), antioxidants (butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), etc.), coloring agents (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG, monosodium glutamate, etc.), sweeteners (dulcin, cyclamate, saccharin, sodium, etc.), flavorings (vanillin, lactones, etc.), leavening agents (alum, D-potassium hydrogen tartrate, etc.), reinforcing agents, emulsifiers, thickeners (pastes), film agents, gum bases, foam suppressants, solvents, and improvers can be added. The above additives are selected according to the type of food and used in an appropriate amount.

[0059] The food composition of the present invention can be manufactured using methods commonly used in the art, and can be manufactured by adding raw materials and ingredients commonly used in the art. Furthermore, unlike conventional pharmaceuticals, it has the advantage of being free of side effects that can occur with long-term use, as it uses food as a raw material, and can be highly portable.

[0060] In another aspect of the present invention, the present invention provides a method for preventing or treating fatty liver disease, comprising administering to a subject a composition comprising ginseng extract-derived ginseng.

[0061] The term "administration" used in the present invention means introducing the composition of the present invention into a patient by any appropriate method, and the route of administration of the composition is not limited as long as it can reach the target tissue, and non-limiting examples of the route of administration include intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, and nasal administration, and oral administration is preferred.

[0062] The composition of the present invention may be administered daily or intermittently, and may be administered once daily or in two or three divided doses. Furthermore, it may be used alone or in combination with other drug treatments. Taking all of the above factors into consideration, it is important to administer the dose that achieves maximum effect with the minimum amount possible without causing side effects, a determination readily made by those skilled in the art.

[0063] In the present invention, the term "subject" means a mammal that is likely to develop fatty liver disease due to environmental or genetic predisposition, exhibits symptoms of fatty liver disease or similar symptoms, or has developed fatty liver disease.

[0064] In another aspect of the present invention, the present invention provides a use of gintonin derived from red ginseng extract for the preparation of an agent for the prevention or treatment of fatty liver disease.

[0065]

[0066] The present invention is susceptible to various modifications and embodiments. Specific embodiments are illustrated in the drawings and described in detail in the following detailed description. However, this is not intended to limit the present invention to specific embodiments, but rather to encompass all modifications, equivalents, and alternatives falling within the spirit and technical scope of the present invention. In describing the present invention, detailed descriptions of related known technologies will be omitted if they are deemed to obscure the gist of the present invention.

[0067]

[0068] [Example]

[0069] Example 1. Preparation of red ginseng extract and isolation of ginseng

[0070] Domestic red ginseng (KRG) was subjected to hot water extraction for 12 hours to obtain a red ginseng extract (the above process was repeated 7 times), and the remaining residue (red ginseng marc, KRGM) was collected and dried to obtain 1 kg of red ginseng marc. The prepared red ginseng marc was ground into small pieces (>3 mm), and 70% (w / v) ethanol was added thereto, followed by reflux cooling extraction and filtration at 80°C for 8 hours to obtain an ethanol extract of red ginseng marc (the above process was repeated 3 times). Subsequently, the red ginseng marc extract was concentrated in a vacuum concentrator, followed by dialysis and freeze-drying to obtain 80 g of red ginseng marc-derived gintonin (KGRM gintonin) (80 g of KRGM / kg of KRG). Furthermore, as a result of analyzing the LPA C18:2 content of the obtained red ginseng marc-derived gintonin, it was confirmed to be as high as the content of the concentrated gintonin fraction generally obtained from white ginseng, as shown in Table 1 below. In addition, the separation process of gintonin derived from the aforementioned red ginseng extract is illustrated in Figure 1.

[0071]

[0072]

[0073] Example 2. Confirmation of the weight loss effect through oral administration of red ginseng extract.

[0074] To confirm the weight loss effect of the red ginseng extract prepared by the method of Example 1, an experiment was conducted in a mouse model induced with obesity by a high-fat diet. The control group was fed a chow diet (5053) from LabDiet, and the obese mice were fed a 60% kcal fat high-fat diet (D12492) from Research diet. The obese group was orally administered 50 mg / kg (low concentration) or 200 mg / kg (high concentration) of red ginseng extract three times a week using a sonde for 25 weeks while feeding the high-fat diet. The body weight was measured once a week to evaluate the weight loss effect of the red ginseng extract. As a result, as can be seen in Figures 2a and 2b, it was confirmed that the obese mouse group (HFD+G200) fed with a high concentration of red ginseng extract showed a significantly lower body weight than the control group from the 13th week onwards, except for the 18th and 19th weeks. These results showed that gintonin contained in red ginseng extract has an anti-obesity effect.

[0075]

[0076] Example 3. Confirmation of increased metabolic rate through oral administration of red ginseng extract.

[0077] In order to confirm the metabolic increase effect of red ginseng extract, a metabolic cage experiment (metabolic cage, CLAMS equipment) was conducted at 12 to 15 weeks after extract intake during the experiment of Example 2, and the changes in metabolic amount of each mouse group were examined. The metabolic cage experiment was conducted under conditions such as maintaining a temperature of 23°C, maintaining a 12-hour light-dark cycle, and providing food and water ad libitum. The metabolic amount was calculated based on the body weight of the mice and the changes in oxygen and carbon dioxide levels over 24 hours. As shown in Figures 3a and 3b, the metabolic amount significantly increased in the obese mouse group (HFD+G200) fed a high concentration of red ginseng extract. In addition, as a result of the activity analysis within the cage, as can be seen in Figure 3c, there was no significant difference in activity compared to the obese control group (HFD+Veh), but the activity tended to be higher in the obese group fed the extract. This experiment indicates that the weight loss effect caused by extract intake is due to an increase in metabolic amount, not a change in food intake.

[0078] Furthermore, as a result of analyzing the mRNA expression of brown fat, as shown in Fig. 4, in the case of the obese mouse group (HFD+G200) fed a high concentration of red ginseng extract, the expression of UCP1, a gene involved in heat production and energy homeostasis in brown fat, was confirmed to have significantly increased. These results showed that the increase in UCP1 increased thermogenesis and metabolic rate, thereby reducing the body weight of the experimental animals.

[0079]

[0080] Example 4. Confirmation of the effect of improving fatty liver through oral administration of red ginseng extract.

[0081] Based on the results of the above examples, we sought to determine whether red ginseng extract could improve fatty liver disease. To this end, we measured and compared the liver weights of mice fed a high concentration of red ginseng extract (HFD+G200) to obese mice fed a high-fat diet (HFD) and a high-fat diet control group (HFD). As shown in Figure 5a, the liver weights of the mice fed the extract were significantly reduced compared to the high-fat diet control group.

[0082] From these results, it was expected that the group that consumed the extract would have alleviated liver fat accumulation, so the liver tissue was stained with H&E and oil red-O to perform a histological analysis. H&E staining shows the tissue structure of the liver, and oil red-O staining can be used to stain neutral fat within the tissue, allowing the proportion of fat accumulated in the liver tissue to be confirmed. The stained photographs were used to calculate the area ratio using the ImageJ program. As a result of the H&E staining analysis, the H&E positive area was significantly higher in the two groups fed the extract (HFD+G50, HFD+G200) compared to the obesity-induced control group (HFD+Veh), as shown in the lower figures of Figures 5b and 5d. In addition, as shown in the upper figures of Figures 5c and 5d, the ratio of fat accumulated in the liver was confirmed by comparing the oil red-O positive area. As a result, the area of ​​lipid droplets in the liver of the mouse group fed the high concentration of the extract was 29.9%, which was reduced in a dose-dependent manner compared to 53.1% in the obesity-induced control group. Through these results, it was found that the red ginseng extract according to the present invention, preferably gintonin contained in the red ginseng extract, has an effect of inhibiting liver fat accumulation.

[0083]

[0084] Although the embodiments described above have been described with limited drawings, those skilled in the art will appreciate that various technical modifications and variations can be applied based on the above. For example, appropriate results can still be achieved even if the described techniques are performed in a different order than described, and / or components of the described systems, structures, devices, circuits, etc. are combined or combined in a different manner than described, or are replaced or substituted with other components or equivalents.

[0085] Therefore, other implementations, other embodiments, and equivalents to the claims also fall within the scope of the claims described below.

[0086]

[0087] This invention was completed with the support of the Korea Institute of Science and Technology (KIST) Institutional Research Project (Account Numbers: 2E32210 and 2E32900, Project Name: Future Brain Science and Technology Development Project: AI-Neural Network Research for Predicting and Overcoming Brain Diseases).

Claims

1. A pharmaceutical composition for the prevention or treatment of fatty liver disease, containing gintonin derived from red ginseng extract as an active ingredient.

2. In paragraph 1, A pharmaceutical composition characterized in that the above gintonin is isolated from a red ginseng extract.

3. In paragraph 2, A pharmaceutical composition characterized in that the red ginseng extract is extracted with at least one solvent selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof.

4. In paragraph 2, A pharmaceutical composition characterized in that the above red ginseng extract is an ethanol extract.

5. In paragraph 1, The above gintonin is a pharmaceutical composition characterized in that it contains lysophosphatidic acid (LPA) as a functional ingredient.

6. In paragraph 1, A pharmaceutical composition characterized in that the above-mentioned liver disease is non-alcoholic fatty liver disease.

7. A food composition for preventing or improving fatty liver disease, containing gintonin derived from red ginseng extract as an active ingredient.

8. In paragraph 7, A food composition characterized in that the above gintonin is separated from a red ginseng extract.

9. In paragraph 8, A food composition characterized in that the red ginseng extract is extracted with at least one solvent selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof.

10. In paragraph 8, A food composition characterized in that the above red ginseng extract is an ethanol extract.

11. In paragraph 7, A food composition characterized in that the above gintonin contains lysophosphatidic acid (LPA) as a functional ingredient.

12. In paragraph 7, A food composition characterized in that the above-mentioned liver disease is non-alcoholic fatty liver disease.

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