Application of jinsi'e glycoside in preparation of products for improving obesity and / or improving glycolipid metabolism

Abstract

This invention belongs to the field of biomedical technology and provides the application of ginsenoside in the preparation of products for improving obesity and / or improving glucose and lipid metabolism. This invention discovers that ginsenoside has a significant improving effect on obesity and glucose and lipid metabolism disorders. Mouse experiments show that, under a high-fat diet, ginsenoside can significantly reduce body weight gain in obese mice, reduce the weight and size of inguinal and epididymal white adipose tissue, significantly improve insulin sensitivity in obese mice, and significantly reduce blood glucose and cholesterol levels in obese mice. It can be used to prepare products for improving obesity and glucose and lipid metabolism, and has broad application prospects.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of ginsenoside in the preparation of products that improve obesity and / or improve glucose and lipid metabolism. Background Technology

[0002] Obesity is a chronic metabolic disease caused by excessive fat accumulation and is closely related to the development of cardiovascular disease, type 2 diabetes, and cancer. In recent years, with changes in lifestyle and dietary structure, the number of obese people worldwide has increased. The causes of obesity include genetics, environment, lifestyle, and the interaction of multiple factors, with excessive intake of high-fat diets being one of the main causes. Currently, controlling diet and increasing exercise are the main means of preventing obesity. However, these interventions have limitations such as long duration, difficulty in maintaining, and a high risk of rebound. Therefore, searching for safe and effective compounds from natural products such as plant extracts to prevent / treat obesity has become a current research hotspot and has significant clinical application value.

[0003] Poliumoside (C 35 H 46 O 19 (Molecular weight 770.72) is a phenylethanol glycoside, a naturally occurring active compound identified as a major component in various medicinal plants, primarily *Callicarpa spicata*. *Callicarpa spicata* glycoside has been reported to possess anti-inflammatory and antioxidant stress-relieving effects and may inhibit the development of colorectal and cervical cancer. Currently, there are no reports of using *Callicarpa spicata* glycoside to improve obesity and related glucose and lipid metabolism. Summary of the Invention

[0004] The purpose of this invention is to provide the application of ginsenoside in the preparation of products that improve obesity and / or improve glucose and lipid metabolism. Ginsenoside has a good effect on improving obesity and related glucose and lipid metabolism disorders. This invention provides new ideas and methods for the effective prevention and treatment of obesity and related glucose and lipid metabolism disorders.

[0005] This invention provides the application of ginsenoside in the preparation of products that improve obesity and / or improve glucose and lipid metabolism.

[0006] As a preferred embodiment, the improvement of glucose and lipid metabolism includes improving glucose and lipid metabolism disorders caused by obesity.

[0007] As a preferred embodiment, the improvement of obesity includes at least one of the following: (1) Reduce weight; (2) Reduce subcutaneous fat weight; (3) Reduce visceral fat weight; (4) Reduce the size of fat cells.

[0008] As a preferred embodiment, the improvement of glucose and lipid metabolism includes at least one of the following: (1) Lowering blood glucose levels; (2) Lower cholesterol levels; (3) Enhance insulin sensitivity.

[0009] As a preferred embodiment, the product includes a drug.

[0010] This invention also provides the use of ginsenoside in the preparation of medicaments for the prevention and / or treatment of obesity-related diseases.

[0011] The present invention also provides a drug for improving obesity and / or improving glucose and lipid metabolism, wherein the raw materials of the drug include an active substance and pharmaceutically acceptable excipients; the active substance includes sclerotinib; and the effective dose of sclerotinib in drinking water is 50-75 μg / mL.

[0012] As a preferred embodiment, the dosage form of the drug includes one or more of the following: tablets, capsules, pills, oral liquid preparations, granules, suspensions, and powders.

[0013] The present invention also provides a method for preparing the drug as described above, comprising the steps of: mixing ginsenoside and pharmaceutically acceptable excipients to obtain the drug.

[0014] Beneficial Effects: This invention provides the application of ginsenosides in the preparation of products for improving obesity and / or improving glucose and lipid metabolism. This invention discovers that ginsenosides have a significant improving effect on obesity and glucose and lipid metabolism disorders. Mouse experiments show that, under a high-fat diet, ginsenosides can significantly reduce body weight gain in obese mice, reduce the weight and size of inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) in obese mice, significantly improve insulin sensitivity in obese mice, and significantly reduce blood glucose and cholesterol levels in obese mice. It can be used to prepare products for improving obesity and glucose and lipid metabolism, and has broad application prospects.

[0015] This invention discloses for the first time a novel application of ginsenosides in the preparation of products related to improving obesity and glucose-lipid metabolism, filling a research gap in the use of ginsenosides for regulating obesity and glucose-lipid disorders, and providing a new direction for the intervention of obesity and its metabolic complications using natural active substances. Compared with the shortcomings of traditional weight loss methods such as dieting and exercise, which are long-term and prone to rebound, ginsenosides, as a natural phenylethyl glycoside active ingredient, are safer, easier to use, and do not require a strict lifestyle, possessing good potential for industrial development and broad market application prospects. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0017] Figure 1 The study investigated the effect of sclerotinib on the area of ​​adipocytes in obese mice. A represents the HE staining morphology of epididymal white adipose tissue (eWAT) in mice; B represents the quantitative statistics of eWAT adipocyte area in each group; C represents the HE staining morphology of inguinal white adipose tissue (iWAT) in mice; D represents the quantitative statistics of iWAT adipocyte area in each group; CON represents the control group; HFD represents the high-fat diet group; HPOL represents the 50 μg / mL sclerotinib group; eWAT represents epididymal white adipose tissue; iWAT represents inguinal white adipose tissue; scale bar is 50 μm. Detailed Implementation

[0018] This invention provides the application of *Gynostemma pentaphyllum* glycoside in the preparation of products for improving obesity and / or improving glucose and lipid metabolism. As one specific embodiment, the improvement of glucose and lipid metabolism includes improving glucose and lipid metabolism disorders caused by obesity. This invention does not specifically limit the source of *Gynostemma pentaphyllum* glycoside; it can be a commercially available product or extracted from natural plants. As one specific embodiment, the extraction source of *Gynostemma pentaphyllum* glycoside includes *Callicarpa spp.* (Guangdong *Callicarpa*). In a specific embodiment of this invention, the *Gynostemma pentaphyllum* glycoside was purchased from Shanghai Yuanye Biotechnology Co., Ltd., product number B20630, with a purity ≥99%.

[0019] The improvement of obesity described in this invention includes at least one of the following: (1) reducing body weight; (2) reducing subcutaneous fat weight; (3) reducing visceral fat weight; and (4) reducing adipocyte size. Experiments of this invention show that, compared with the control group, a high-fat diet significantly increased the body weight of mice starting from week 2 of feeding. P <0.05%, leading to obesity. Compared with the high-fat diet group, the addition of 50 μg / mL of ginsenoside to the drinking water significantly reduced the body weight of mice from week 3 to week 10. P <0.05, and significantly reduced body weight gain in mice ( P <0.05. Further analysis of the white adipose tissue of mice showed that a high-fat diet significantly increased the weight of eWAT and iWAT (<0.05). P <0.05, increased the area of ​​adipocytes ( P <0.001). Compared with the high-fat diet group, the addition of 50 μg / mL of ginsenoside to the drinking water reduced the eWAT and iWAT weights in obese mice ( P <0.05, significantly reducing the area of ​​adipocytes ( P <0.001).

[0020] The improvement of glucose and lipid metabolism described in this invention includes at least one of the following: (1) reducing blood glucose levels; (2) reducing cholesterol levels; and (3) enhancing insulin sensitivity. Experiments of this invention show that, compared with the control group, feeding mice a high-fat diet significantly increased blood glucose levels (…). P <0.05) and cholesterol ( P The levels of glucose and cholesterol induced by a high-fat diet were significantly reduced by 50 μg / mL of ginsenoside in drinking water, while the addition of ginsenosides to drinking water significantly improved the abnormalities in blood glucose and cholesterol levels induced by a high-fat diet. After intraperitoneal injection of insulin, the AUC of mice in the high-fat model group was significantly increased compared to the control group (<0.01). P <0.05%, adding 50 μg / mL of ginsenoside to drinking water tends to reduce AUC ( P =0.06). Therefore, ginsenoside has the effect of improving insulin sensitivity in obese mice.

[0021] In one specific embodiment, the product includes food, health food, or medicine. In another specific embodiment, the ginseng and ginseng described in this invention can be processed into various dosage forms such as tablets, capsules, pills, oral liquid preparations, granules, suspensions, or powders, suitable for general food, health food, and pharmaceutical product systems, and can be used in industrial production with commonly available edible excipients and additives.

[0022] This invention also provides the use of ginsenoside in the preparation of medicaments for the prevention and / or treatment of obesity-related diseases.

[0023] This invention also provides a drug for improving obesity and / or improving glucose and lipid metabolism, wherein the raw materials of the drug include an active substance and pharmaceutically acceptable excipients; the active substance includes sclerotinib. As one specific embodiment, the dosage form of the drug includes one or more of tablets, capsules, pills, oral liquid preparations, granules, suspensions, and powders. As one specific embodiment, the route of administration of the drug includes oral administration.

[0024] The effective dose of ginsenoside in drinking water according to the present invention is 50~75 μg / mL. As a specific embodiment, the effective dose of ginsenoside in drinking water can be any value among 50 μg / mL, 51 μg / mL, 52 μg / mL, 53 μg / mL, 54 μg / mL, 55 μg / mL, 56 μg / mL, 57 μg / mL, 58 μg / mL, 59 μg / mL, 60 μg / mL, 61 μg / mL, 62 μg / mL, 63 μg / mL, 64 μg / mL, 65 μg / mL, 66 μg / mL, 67 μg / mL, 68 μg / mL, 69 μg / mL, 70 μg / mL, 71 μg / mL, 72 μg / mL, 73 μg / mL, 74 μg / mL, and 75 μg / mL, as well as the midpoint between any two values. The embodiments of the present invention demonstrate that 50 μg / mL of ginsenoside can significantly reduce weight gain and white fat accumulation induced by a high-fat diet, improve glucose and lipid metabolism in obese mice, including improving insulin sensitivity and reducing blood glucose and blood cholesterol levels.

[0025] The present invention also provides a method for preparing the drug as described above, comprising the steps of: mixing ginsenoside and pharmaceutically acceptable excipients to obtain the drug.

[0026] To further illustrate the present invention, the application of the ginsenoside provided by the present invention in the preparation of products for improving obesity and / or improving glucose and lipid metabolism is described in detail below with reference to the embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0027] Unless otherwise specified, the present invention does not have special requirements for the raw materials used in the preparation, and commercially available products well known to those skilled in the art can be used.

[0028] Example 1 1. Experimental animals Thirty-six 8-week-old male, SPF-grade C57BL / 6 mice (purchased from Beijing Spefol Biotechnology Co., Ltd.) were randomly divided into four groups of nine mice each: control group (CON), high-fat model group (HFD), 25 μg / mL silymarin group (HFD+LPOL), and 50 μg / mL silymarin group (HFD+HPOL). During the experiment, the mice's food and water intake were not restricted by any factors.

[0029] 2. Experimental Design (1) Animal modeling, grouping and treatment Control group: fed with control feed (fat calories 10%, purchased from Beijing Huafukang Biotechnology Co., Ltd., product number H10010), and drinking water was distilled water; High-fat model group: fed with high-fat diet (fat calories accounted for 60%, purchased from Beijing Huafukang Biotechnology Co., Ltd., product number H10060), and drinking water was distilled water; Jinshican glycoside group: fed a high-fat diet, with 25 μg / mL and 50 μg / mL of Jinshican glycoside added to the drinking water, respectively. Jinshican glycoside was purchased from Shanghai Yuanye Biotechnology Co., Ltd., product number B20630, with a purity ≥99%.

[0030] (2) Indicator detection The experiment lasted for 13 weeks, with mouse body weight recorded weekly. In week 11, mice underwent a glucose tolerance test by intraperitoneal injection of a 2 g / kg body weight glucose solution after a 6-hour fast in the morning. Blood was collected via the caudal vein, and blood glucose levels were measured using a glucometer at fasting and at 15, 30, 60, 90, and 120 minutes after glucose injection. In week 12, mice underwent an insulin tolerance test by intraperitoneal injection of 0.75 U / kg body weight insulin after a 6-hour fast in the morning. Blood was collected via the caudal vein, and blood glucose levels were measured using a glucometer at fasting and at 15, 30, 60, 90, and 120 minutes after insulin injection. The area under the blood glucose curve (AUC) was calculated based on the blood glucose values ​​at each time point in both the glucose and insulin tolerance tests. The AUC was used to assess the mice's glucose tolerance and insulin sensitivity; a lower AUC indicated stronger glucose tolerance and insulin sensitivity.

[0031] (3) Data processing The original data was organized using Excel 2016, and one-way ANOVA was performed using SAS (SAS 9.2) software. Tukey's method was used for multiple comparisons. The results were then analyzed. P <0.05 indicates a significant difference. P <0.01 indicates a highly significant difference, and 0.05 ≤ P A value ≤0.10 indicates a trend. Data are expressed as mean ± standard deviation.

[0032] 3. Experimental Results As shown in Table 1, compared with the control group, the high-fat diet significantly increased the body weight of mice starting from the second week of feeding ( P <0.05%, leading to obesity. Compared with the high-fat diet group, the addition of 50 μg / mL of ginsenoside to the drinking water significantly reduced the body weight of mice from week 3 to week 10. P <0.05, and significantly reduced body weight gain in mice ( P<0.05). Adding 25 μg / mL of sclerotinib to drinking water had no significant effect on body weight and weight gain in mice fed a high-fat diet.

[0033] As shown in the glucose tolerance test (Table 2), after intraperitoneal injection of glucose, the addition of ginsenosides to drinking water had no significant effect on blood glucose levels compared with the high-fat model group.

[0034] As shown in the insulin tolerance test (Table 3), after intraperitoneal injection of insulin, the AUC of mice in the high-fat model group was significantly increased compared with the control group. P <0.05%, adding 50 μg / mL of ginsenoside to drinking water tends to reduce AUC ( P =0.06). Therefore, ginsenoside has the effect of improving insulin sensitivity in obese mice.

[0035] Table 1. Effects of sclerotin on body weight (g) in obese mice.

[0036] Note: Compared with the control group, Δ P <0.05, ΔΔ P <0.01; compared with the high-fat model group, P <0.05, P <0.01.

[0037] Table 2. Effects of sclerotin on glucose tolerance in obese mice (mmol / L)

[0038] Note: Compared with the control group, Δ P <0.05, ΔΔ P <0.01.

[0039] Table 3. Effects of sclerotin on insulin sensitivity in obese mice (mmol / L)

[0040] Note: Compared with the control group, Δ P <0.05, ΔΔ P <0.01.

[0041] Example 2 1. Sample collection and index testing Mice fed for 13 weeks as in Example 1 were fasted for 12 hours, then euthanized under anesthesia. Serum samples were collected and stored at -80°C for the detection of blood glucose, triglycerides, and cholesterol. The reagent kits used were purchased from Nanjing Jiancheng Biotechnology Institute (China), and the procedures were performed according to the kit instructions.

[0042] The epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) were separated and weighed. A portion of eWAT and iWAT was harvested and fixed in 4% paraformaldehyde for at least 48 hours. The preparation of tissue sections of the adipose tissue included dehydration, clearing, preparation of paraffin blocks, sectioning, baking, hydration, hematoxylin staining, eosin staining, mounting, and image acquisition.

[0043] 2. Data Processing The original data was organized using Excel 2016, and one-way ANOVA was performed using SAS (SAS 9.2) software. Tukey's method was used for multiple comparisons. The results were then analyzed. P <0.05 indicates a significant difference. P <0.01 indicates a highly significant difference, and 0.05 ≤ P A value ≤0.10 indicates a trend. Data are expressed as mean ± standard deviation.

[0044] 3. Experimental Results Table 4 shows that, compared with the control group, feeding a high-fat diet significantly increased blood glucose levels in mice. P <0.05) and cholesterol ( P The levels of blood glucose and cholesterol were reduced to <0.01, while the addition of 50 μg / mL of ginsenoside to drinking water significantly improved the abnormal blood glucose and cholesterol levels caused by a high-fat diet.

[0045] Further analysis of the white adipose tissue in mice revealed that a high-fat diet significantly increased the weight of eWAT and iWAT. P <0.05, Table 5), increased adipocyte area ( P <0.001, Figure 1 Compared with the high-fat diet group, the addition of 50 μg / mL of ginsenoside to the drinking water reduced the eWAT and iWAT weights in obese mice. P <0.05, Table 5), significantly reduced adipocyte area ( P <0.001, Figure 1 ).

[0046] Table 4. Effects of ginsenoside on blood glucose and blood lipid levels in obese mice (mmol / L)

[0047] Note: Compared with the control group, Δ P <0.05, ΔΔ P <0.01; compared with the high-fat model group, P <0.05, P <0.01.

[0048] Table 5. Effect of sclerotin on adipose tissue weight in obese mice (g)

[0049] Note: Compared with the control group, Δ P <0.05, ΔΔ P <0.01; compared with the high-fat model group, P <0.05, P <0.01.

[0050] Therefore, it can be seen that ginsenoside can significantly reduce weight gain and white fat accumulation caused by a high-fat diet, improve glucose and lipid metabolism in obese mice, including improving insulin sensitivity, reducing blood glucose and blood cholesterol levels, with 50 μg / mL being the effective dose.

[0051] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. Application of ginsenoside in the preparation of products that improve obesity and / or improve glucose and lipid metabolism.

2. The application according to claim 1, characterized in that, The improvement of glucose and lipid metabolism includes improving glucose and lipid metabolism disorders caused by obesity.

3. The application according to claim 1, characterized in that, The improvement of obesity includes at least one of the following: (1) Reduce weight; (2) Reduce subcutaneous fat weight; (3) Reduce visceral fat weight; (4) Reduce the size of fat cells.

4. The application according to claim 1, characterized in that, The improvement of glucose and lipid metabolism includes at least one of the following: (1) Lower glucose levels; (2) Lower cholesterol levels; (3) Enhance insulin sensitivity.

5. The application according to claim 1, characterized in that, The products include pharmaceuticals.

6. Application of ginsenoside in the preparation of drugs for the prevention and / or treatment of obesity-related diseases.

7. A drug for improving obesity and / or improving glucose and lipid metabolism, characterized in that, The raw materials of the drug include active substances and pharmaceutically acceptable excipients; the active substances include ginsenosides. The effective dosage of the ginsenoside for use in drinking water is 50-75 μg / mL.

8. The medicament according to claim 7, characterized in that, The dosage form of the drug includes one or more of the following: tablets, capsules, pills, oral liquid preparations, granules, suspensions, and powders.

9. The method for preparing the drug according to claim 7 or 8, characterized in that, The process includes the following steps: mixing ginsenoside and pharmaceutically acceptable excipients to obtain the drug.

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