Use of bougainvillea glabra triterpenoid saponin compound

Abstract

Provided is use of a Bougainvillea glabra triterpenoid saponin compound. Particularly, the present invention relates to use of a Bougainvillea glabra triterpenoid saponin compound having a structure of formula (I) in the preparation of a pharmaceutical composition for relieving or ameliorating obesity. The compound having the structure of formula (I) can significantly reduce the body fat rate of obese people. The body fat rate of the 80 mg / kg administration group is reduced by 11.17% compared with the body fat rate of the obesity group. In addition, the compound having the structure of formula (I) can significantly reduce the level of triglyceride (TG) in the liver of DIO mice and improve the pathological condition of liver tissues, indicating that the compound having the structure of formula (I) can be used for ameliorating non-alcoholic fatty liver disease (hepatitis) / liver cirrhosis.

Description

Application of a bougainvillea triterpenoid saponin compound Technical Field

[0001] The invention belongs to the field of medical applications, and particularly relates to an application of a bougainvillea triterpenoid saponin compound. Background Art

[0002] Overweight and obesity are defined as abnormal or excessive fat accumulation that can harm health. They are chronic, recurrent, and progressive diseases and have become a major public health issue in my country and the world. According to the World Obesity Atlas published on the official website of the World Obesity Federation in 2023, the overweight / obesity rate (overweight is defined as BMI ≥ 25 kg / m2) among people aged ≥ 5 years old worldwide is 2.3% and 1.1% respectively. 2 Obesity is defined as BMI ≥ 30 kg / m 2 ) will rapidly increase from 38% in 2020 to 51% in 2035, and the number of people will climb from 2.6 billion in 2020 to more than 4 billion in 2035; the obesity rate will rise from 14% in 2020 to 24% in 2035, and the number of people will reach nearly 2 billion. The latest "Report on the Nutrition and Chronic Disease Status of Chinese Residents (2020)" shows that the overweight rate of Chinese adults (≥18 years old) is 34.3%, and the obesity rate is 16.4%, and more than half of the adults are overweight / obese. Calculated in terms of absolute population, there are already 600 million overweight and obese people in the country, and the number of obese adults is second only to the United States. If we follow the Chinese standard (overweight is defined as BMI ≥ 24kg / m 2 Obesity is defined as BMI ≥ 28 kg / m 2 ), China may already be the country with the largest number of obese people in the world.

[0003] Overweight and obesity are established risk factors for major chronic noncommunicable diseases (NCDs). In 2019, deaths due to overweight and obesity accounted for 11.1% of all NCD-related deaths in China, a significant increase from 5.7% in 1990. This has resulted in significant healthcare expenditures for the management of NCDs in my country. The global market for weight loss drugs is expected to grow dramatically from US$2.82 billion in 2022 to over US$13 billion in 2029.

[0004] GLP-1 is an intestinal insulinotropic factor that stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner and reduces glucagon secretion from pancreatic alpha cells, thereby lowering blood sugar. GLP-1 also protects pancreatic beta cells, inhibits gastric emptying, and reduces appetite. Its "incretin effect" accounts for over 50% of the total insulin secreted after a meal. It also has a wide range of extrapancreatic metabolic regulatory effects, including weight loss, appetite suppression, and cardiovascular benefits.

[0005] GLP-1 receptor agonists are GLP-1 analogs with the following main effects: ① Directly promoting the synthesis and secretion of insulin by binding to the GLP-1 receptors on pancreatic islet cells. At the same time, they can also promote the secretion of somatostatin, indirectly inhibiting the secretion of glucagon, thereby achieving the purpose of lowering fasting blood sugar and postprandial blood sugar. ② They can act on the GLP-1 receptors in the gastrointestinal tract, inhibit gastrointestinal motility, delay the absorption of substances, and reduce food intake. At the same time, they can also act on the GLP-1 receptors in the central nervous system to achieve the purpose of central appetite suppression. ③ Not only do they have cardiovascular protective effects, but they have also been preliminarily verified in multiple indications such as kidney disease, liver disease, Alzheimer's disease, peripheral arterial disease, etc. Some drugs already have clinical data readouts, and have huge research and development potential.

[0006] In the prior art, patent CN104910240B reports that triterpenoid saponin compounds of Bougainvillea glabra can be used as blood sugar lowering drugs for type 2 diabetes. However, there are no reports on triterpenoid saponin compounds of Bougainvillea glabra being used as lipid-lowering and weight-reducing drugs for obese people without type 2 diabetes.

[0007] Therefore, there is an urgent need in this field to develop weight loss drugs for obese people without type 2 diabetes. Summary of the Invention

[0008] The purpose of the present invention is to provide a weight loss drug for obese people without type 2 diabetes, and specifically relates to the use of a triterpenoid saponin compound of Bougainvillea glabra.

[0009] In the first aspect of the present invention, there is provided a use of a triterpenoid saponin compound of Bougainvillea glabra having a structure of formula (I) for preparing a pharmaceutical composition for alleviating or improving obesity.

[0010] In another preferred embodiment, the pharmaceutical composition is administered to obese people.

[0011] In another preferred embodiment, the obese population is an obese population without type 2 diabetes.

[0012] In another preferred embodiment, the fasting blood glucose of the obese people is ≤9.2 mmol / L.

[0013] In another preferred embodiment, the daily dose of the compound of formula (I) in the pharmaceutical composition is 25-600 mg.

[0014] In another preferred embodiment, the alleviation or improvement of obesity refers to improvement in one or more indicators selected from the following group: body fat percentage, adipose tissue content, liver triglyceride content, overweight, or a combination thereof.

[0015] In another preferred embodiment, the alleviation or improvement of obesity refers to one or more effects selected from the following group:

[0016] (a) Decreased body fat percentage;

[0017] (b) decreased adipose tissue content;

[0018] (c) decreased liver triglyceride content;

[0019] (d) weight loss;

[0020] Herein, the reduction means that the corresponding index of the subject after administration of the pharmaceutical composition is decreased compared with the subject not administered with the pharmaceutical composition, and the difference is significant.

[0021] In another preferred embodiment, the pharmaceutical composition is used to significantly reduce the body fat percentage of obese people, and the significant reduction refers to: (body fat percentage of obese people who have not taken weight-loss drugs - body fat percentage of obese people after taking weight-loss drugs) / body fat percentage of obese people who have not taken weight-loss drugs > 10%, preferably > 20%.

[0022] In another preferred embodiment, the body fat rate is human body fat content (mass) / body weight (mass)×100%.

[0023] In another preferred example, the pharmaceutical composition is used to significantly reduce the weight of adipose tissue in obese people, and the adipose tissue is selected from the following group: perirenal fat, abdominal fat, and subcutaneous fat, and the significant decrease means: (perirenal fat of obese people after administration of weight-loss drugs / body weight) × 100% < 1.7%, (abdominal fat of obese people after administration of weight-loss drugs) / body weight × 100% < 5%, (subcutaneous fat of obese people after administration of weight-loss drugs / body weight) × 100% < 3.4%.

[0024] In another preferred embodiment, the pharmaceutical composition is used to significantly reduce the triglyceride content in the liver, and the significant reduction refers to: (triglyceride content of obese people who have not taken weight-loss drugs - triglyceride content of obese people after taking weight-loss drugs) / triglyceride content of obese people who have not taken weight-loss drugs > 40%, preferably > 50%.

[0025] In another preferred embodiment, the triglyceride content is triglyceride mass in liver / liver mass.

[0026] In the second aspect of the present invention, a pharmaceutical preparation is provided, comprising as an active ingredient a compound of formula (I) as described in the first aspect, and pharmaceutically acceptable adjuvants, carriers or excipients.

[0027] In another preferred embodiment, the preparation is an oral preparation or a non-oral preparation.

[0028] In another preferred embodiment, the preparation includes a liquid preparation, a semisolid preparation, or a solid preparation.

[0029] In another preferred embodiment, the preparation includes: powder, granule, capsule, mixture, powder, injection, tincture, oral solution, tablet, lozenge, or pill.

[0030] In the third aspect of the present invention, there is provided a use of the preparation according to the second aspect for preparing a weight loss drug.

[0031] In another preferred embodiment, the weight loss has one or more characteristics selected from the following group:

[0032] (a) Decreased body fat percentage;

[0033] (b) decreased adipose tissue content;

[0034] (c) decreased liver triglyceride content;

[0035] (d) weight loss;

[0036] Wherein, the reduction means that the corresponding index of the subject after administration of the pharmaceutical composition is decreased compared with the subject not administered with the pharmaceutical composition, and the difference is significant, and the index is selected from the following group: body fat percentage, adipose tissue content, liver triglyceride content, and body weight.

[0037] In a fourth aspect of the present invention, a method for weight loss is provided, comprising the steps of administering a medically effective amount of the weight loss drug of the first aspect or the pharmaceutical preparation of the second aspect to a subject in need thereof.

[0038] In another preferred embodiment, the subject is an obese person.

[0039] In another preferred embodiment, the obese population is non-type 2 diabetic obese population.

[0040] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 shows the effects of multiple administrations of triterpenoid saponin compounds from Bougainvillea var. lucidum on the body weight of mice, wherein a in Figure 1 is the effect of multiple administrations of triterpenoid saponin compounds from Bougainvillea var. lucidum on the random body weight of obese model mice, b in Figure 1 is the ratio of the endpoint body weight after multiple administrations of triterpenoid saponin compounds from Bougainvillea var. lucidum to the model control group, and c in Figure 1 is the ratio of the endpoint body weight after multiple administrations of triterpenoid saponin compounds from Bougainvillea var. lucidum to the model control group.

[0042] FIG2 shows the effects of multiple administration of triterpenoid saponin compounds from Bougainvillea glabra on the body composition of obese model mice.

[0043] Figure 3 shows the effects of multiple administration of triterpenoid saponin compounds from Bougainvillea glabra on blood lipids in DIO mice, wherein a in Figure 3 is triglyceride TG; b in Figure 3 is total cholesterol TC; c in Figure 3 is high-density lipoprotein HDL; and d in Figure 3 is low-density lipoprotein LDL.

[0044] FIG4 shows the effects of multiple administration of triterpenoid saponin compounds from Bougainvillea glabra on the adipose tissue weight / body weight ratio of obese mice.

[0045] FIG5 shows the effects of multiple administration of triterpenoid saponin compounds from Bougainvillea glabra on the TC and TG contents in the liver of obese mice, wherein a in FIG5 is TG and b in FIG5 is TC.

[0046] Figure 6 shows the effects of multiple administration of triterpenoid saponins from Bougainvillea glabra on liver pathological conditions in obese mice, wherein Figure 6a is HE staining and Figure 6b is Oil Red staining. DETAILED DESCRIPTION

[0047] After extensive and in-depth research and numerous experimental screenings, the inventors unexpectedly discovered for the first time that the bougainvillea triterpenoid saponin compound of the present invention, structured as formula (I), can be used to prepare a pharmaceutical composition for alleviating or improving obesity. The compound of the present invention, structured as formula (I), can significantly reduce the body fat percentage of obese people, with the 80 mg / kg administration group showing an 11.17% reduction in body fat percentage compared to the obese group. Furthermore, the compound of the present invention, structured as formula (I), can significantly reduce triglyceride (TG) levels in the liver of DIO mice and improve liver tissue pathology, suggesting that the compound of the present invention can be used to improve non-alcoholic fatty liver disease (NSALD) / cirrhosis. The present invention was completed on this basis.

[0048] Terminology

[0049] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0050] As used herein, the terms "comprise," "include," and "contain" are used interchangeably to include not only closed definitions but also semi-closed and open definitions. In other words, the terms include "consisting of," "consisting essentially of."

[0051] In the present invention, the terms "compound with formula (I) structure", "triterpenoid saponin compound of Bougainvillea glabra with formula (I) structure", "triterpenoid saponin compound of Bougainvillea glabra of the present invention", and "triterpenoid saponin compound of Bougainvillea glabra" can be used interchangeably.

[0052] As used herein, the term "pharmaceutically acceptable excipient, carrier or vehicle" refers to a substance that is suitable for use in humans and / or animals without excessive adverse side effects (such as toxicity, irritation and allergic reactions), that is, has a reasonable benefit / risk ratio.

[0053] As used herein, the term "effective amount" refers to an amount that produces a function or activity in humans and / or animals and is acceptable to humans and / or animals. Those skilled in the art will appreciate that the "effective amount" may vary depending on the form of the pharmaceutical composition, the severity of the disease, and the combination with other drugs.

[0054] The bougainvillea triterpenoid saponin compound of the present invention

[0055] The bougainvillea triterpenoid saponin compound in the present invention has the structure of formula (I):

[0056] The method for preparing the triterpenoid saponin compound of Bougainvillea glabra comprises the following steps: taking branches and leaves of Bougainvillea glabra, drying and crushing them, and then cold-immersing and fully extracting them with 90% methanol at room temperature to obtain a methanol extract; suspending the methanol extract in water, and then fully extracting them with ethyl acetate and n-butanol in sequence; repeatedly separating and purifying the ethyl acetate portion and the n-butanol portion using various chromatography columns such as cellulose, Sephadex LH-20, and RP-18, and then combining the TLC detection method of the tripteride saponin to obtain the Bougainvillea glabra tripteride saponin.

[0057] Preparation and administration

[0058] The present invention provides a preparation containing a compound of formula (I) as an active ingredient and a pharmaceutically acceptable adjuvant, carrier or excipient. The preparation may further contain a pharmaceutically or health product acceptable carrier.

[0059] There are no particular limitations on the dosage form of the preparation of the present invention, and any dosage form suitable for mammals may be used. Preferably, the dosage form may include tablets, capsules, granules, pills, mixtures, powders, oral liquids, buccal tablets, or aerosols. From the perspective of ease of preparation, administration, or administration, the preferred composition is a solid-state preparation. Oral administration is preferred.

[0060] The preparations of the present invention may be added with various conventional carriers and / or excipients required for preparing different dosage forms. The excipients described herein are pharmaceutically acceptable excipients and include dextrin, lactose, sodium bicarbonate, citric acid, sodium hydroxymethyl starch, micropowdered silica gel, starch, soluble starch, polyethylene glycol, or magnesium stearate. Conventional methods for preparing traditional Chinese medicines may be used to prepare the preparations into any commonly used dosage form, such as tablets, capsules, granules, capsules, pills, and powders.

[0061] Some examples of pharmaceutically acceptable excipients include cellulose and its derivatives (such as methyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, etc.), gelatin, talc, solid lubricants (such as stearic acid, magnesium stearate), calcium sulfate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (such as propylene glycol, glycerol, mannitol, sorbitol, etc.), emulsifiers (such as Tween), wetting agents (such as sodium lauryl sulfate), buffers, chelating agents, thickeners, pH regulators, transdermal enhancers, colorants, flavorings, stabilizers, antioxidants, preservatives, antibacterial agents, pyrogen-free water, etc.

[0062] The formulation of the present invention can be directly used to prepare a drug for weight loss. The formulation of the present invention may also contain other drugs that are effective for weight loss. Preferably, the formulation of the present invention can reduce the weight of obese people.

[0063] The formulations of the present invention are typically administered at a dose of 20-600 mg per day, preferably in one to two divided doses per day, or in a sustained-release form. The specific dosage will, of course, vary depending on the mode of administration, dosage form, and severity of the condition being treated, and the route of administration, all of which are within the skill of the skilled physician. Administration can be by conventional routes, including, but not limited to, oral, intramuscular, transdermal, or topical administration. Oral administration is preferred.

[0064] The present invention also provides a method for weight loss, comprising administering a medically effective amount of the weight loss drug or pharmaceutical formulation of the present invention to a subject in need thereof. The subject can be a human or a non-human mammal (e.g., a dog, pig, cat, monkey, sheep, horse, cattle, etc.).

[0065] use

[0066] In the present invention, the bougainvillea triterpenoid saponin compound of formula (I) is used to prepare a pharmaceutical composition for alleviating or improving obesity.

[0067] In one embodiment of the present invention, the pharmaceutical composition is administered to obese people, preferably obese people without type 2 diabetes.

[0068] Preferably, the fasting blood glucose of the obese people is ≤9.2 mmmol / L.

[0069] In one embodiment of the present invention, the daily dose of the compound of formula (I) in the pharmaceutical composition is 20-600 mg.

[0070] In the present invention, the alleviation or improvement of obesity refers to the improvement of one or more indicators selected from the following group: body fat percentage, adipose tissue content, liver triglyceride content, overweight, or a combination thereof.

[0071] Preferably, the alleviation or improvement of obesity refers to one or more effects selected from the following group:

[0072] (a) Decreased body fat percentage;

[0073] (b) decreased adipose tissue content;

[0074] (c) decreased liver triglyceride content;

[0075] (d) weight loss;

[0076] Herein, the reduction means that the corresponding index of the subject after administration of the pharmaceutical composition is decreased compared with the subject not administered with the pharmaceutical composition, and the difference is significant.

[0077] In a preferred embodiment of the present invention, the pharmaceutical composition can significantly reduce the body fat percentage of obese people, and the significant reduction refers to: (body fat percentage of obese people who have not taken weight-loss drugs - body fat percentage of obese people after taking weight-loss drugs) / body fat percentage of obese people who have not taken weight-loss drugs > 10%, preferably > 20%.

[0078] In the present invention, the body fat rate is human body fat content (mass) / body weight (mass)×100%.

[0079] In a preferred embodiment of the present invention, the pharmaceutical composition can significantly reduce the weight of adipose tissue in obese people, and the adipose tissue is selected from the following group: perirenal fat, abdominal fat, and subcutaneous fat. The significant decrease means: (perirenal fat of obese people after administration of weight-loss drugs / body weight) × 100% < 1.7%, (abdominal fat of obese people after administration of weight-loss drugs) / body weight × 100% < 5%, (subcutaneous fat of obese people after administration of weight-loss drugs / body weight) × 100% < 3.4%.

[0080] In a preferred embodiment of the present invention, the pharmaceutical composition can significantly reduce the triglyceride content in the liver, and the significant reduction refers to: (triglyceride content of obese people who have not taken weight-loss drugs - triglyceride content of obese people after taking weight-loss drugs) / triglyceride content of obese people who have not taken weight-loss drugs > 40%, preferably > 50%.

[0081] In the present invention, the triglyceride content is triglyceride mass in liver / liver mass.

[0082] The present invention provides a use of a pharmaceutical preparation for preparing a weight-loss drug.

[0083] In the present invention, the pharmaceutical composition comprises the triterpenoid saponin compound of the formula (I) as an effective ingredient, and pharmaceutically acceptable adjuvants, carriers or excipients.

[0084] Preferably, the preparation is an oral preparation or a non-oral preparation.

[0085] Preferably, the preparation includes a liquid preparation, a semisolid preparation, or a solid preparation.

[0086] Preferably, the preparation includes: powder, granule, capsule, mixture, powder, injection, tincture, oral solution, tablet, lozenge, or pill.

[0087] In one embodiment of the present invention, the weight loss has one or more characteristics selected from the following group:

[0088] (a) Decreased body fat percentage;

[0089] (b) decreased adipose tissue content;

[0090] (c) decreased liver triglyceride content;

[0091] (d) weight loss;

[0092] Wherein, the reduction means that the corresponding index of the subject after administration of the pharmaceutical composition is decreased compared with the subject not administered with the pharmaceutical composition, and the difference is significant, and the index is selected from the following group: body fat percentage, adipose tissue content, liver triglyceride content, and body weight.

[0093] Compared with the prior art, the present invention has the following beneficial effects:

[0094] 1. The compound of formula (I) of the present invention can be used to prepare a pharmaceutical composition for alleviating or improving obesity, which can significantly reduce the weight of obese people.

[0095] 2. The pharmaceutical composition of the present invention can reduce the weight of adipose tissue, including perirenal fat, abdominal fat, and subcutaneous fat, thereby significantly reducing the body fat rate of obese people. The body fat rate of the 80 mg / kg administration group was reduced by 11.17% compared with the obese group.

[0096] 3. The pharmaceutical composition of the present invention can significantly reduce the triglyceride TG level in the liver of DIO mice and improve the pathological condition of liver tissue, suggesting that the compound of formula (I) of the present invention can be used to improve non-alcoholic fatty liver (inflammation) / cirrhosis.

[0097] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which specific conditions are not specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.

[0098] Example 1: Study on the effect of the Bougainvillea triterpenoid saponin compound of the present invention on the body weight of DIO mice

[0099] Experimental Methods: C57BL / 6J mice (5 weeks old and 12 weeks of high-fat diet induction, hereafter referred to as DIO mice) were acclimated to a high-fat diet. After 2 weeks of acclimation, they were randomly divided into seven groups based on body weight: a model control group, a 0.1-dose group (20 mg / kg, 40 mg / kg, and 80 mg / kg), and a group of normal C57BL / 6J mice as a control. Each group was dosed once daily. Body weight and food intake were monitored daily. An insulin tolerance test was performed on day 31 of drug administration, and body fat was measured on day 32 of drug administration. Mice were sacrificed on day 33 of drug administration. After the end of the experiment, adipose tissues and organs were isolated and weighed, and plasma free fatty acids, total cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase, among other biochemical parameters, were measured.

[0100] result

[0101] 1.1 Repeated administration of triterpenoid saponins from Bougainvillea glabra significantly reduced the body weight of DIO mice

[0102] As shown in Tables 1-5 and Figure 1, the random body weight of the high-fat diet-induced obesity model mice was always significantly higher than that of the normal control group during the experiment and maintained at a relatively stable level.

[0103] The triterpenoid saponin compound of Bougainvillea glabra was administered once daily for multiple doses for 30 days, which significantly reduced the random body weight of DIO mice. The effect lasted until the end of the experiment. The average random body weight reduction rates of the 20 mg / kg, 40 mg / kg, and 80 mg / kg dose groups were 0.94%, 7.22%, and 20.05%, respectively. The results are shown in Table 5.

[0104] Table 1: Effects of multiple administration of triterpenoid saponins from Bougainvillea glabra on body weight (g) of DIO C57 mice

[0105] Table 2: Effects of multiple administration of triterpenoid saponins from Bougainvillea glabra on body weight (g) of DIO C57 mice (continued)

[0106] Table 1: Effects of multiple administration of triterpenoid saponins from Bougainvillea glabra on body weight (g) of DIO C57 mice (continued)

[0107] Table 4: Weight loss rate (%) of DIO C57 mice after repeated administration of triterpenoid saponins from Bougainvillea glabra

[0108] Table 2: Weight loss rate (%) of DIO C57 mice after repeated administration of triterpenoid saponins from Bougainvillea glabra (continued)

[0109] 1.2 Repeated administration of triterpenoid saponins from Bougainvillea glabra significantly reduced body fat content in DIO mice

[0110] As shown in Figure 2 and Table 6, once-daily, multiple-dose administration of the Bougainvillea triterpenoid saponin compound for 30 days significantly reduced body fat percentage and increased lean body mass in DIO mice. After 30 days of dosing, the average body fat percentages in the 20 mg / kg, 40 mg / kg, and 80 mg / kg groups were 40.49%, 39.43%, and 30.46%, respectively, demonstrating a dose-dependent pattern.

[0111] Table 3: Effects of chronic administration of triterpenoid saponins from Bougainvillea glabra on body composition of DIO C57 mice

[0112] 1.3 Effects of multiple administration of triterpenoid saponins from Bougainvillea glabra on blood lipids in DIO mice

[0113] As shown in Figure 3 and Table 7, DIO mice exhibited lipid metabolism disorders, with significantly elevated plasma total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Multiple daily administration of the bougainvillea triterpenoid saponin compound for 30 days had no significant effect on the lipid profile of DIO mice.

[0114] Table 4: Effects of long-term administration of triterpenoid saponins from Bougainvillea glabra on blood lipids in DIO C57 mice

[0115] 1.4 Effects of multiple administration of triterpenoid saponins from Bougainvillea glabra on adipose tissue weight in obese mice

[0116] As shown in Figure 4 and Table 8, after once-daily administration of the triterpenoid saponin compound of Bougainvillea glabra for 30 days, the 80 mg / kg dose group of the triterpenoid saponin compound of Bougainvillea glabra significantly reduced the ratio of perirenal fat, abdominal fat, and subcutaneous fat weight to body weight in obese model mice.

[0117] Table 8: Effects of long-term administration of triterpenoid saponins from Bougainvillea glabra on adipose tissue and fat-to-body weight ratio in DIO C57 mice

[0118] 1.5 Effects of long-term administration of triterpenoid saponins from Bougainvillea odorifera on TC and TG in the liver of obese mice

[0119] As can be seen from Figure 5 and Table 9, long-term administration of the triterpenoid saponin compound of Bougainvillea glabra once a day for 30 days had no significant effect on the TC content. Long-term administration of the triterpenoid saponin compound of Bougainvillea glabra could reduce the TG content in the liver of mice in a dose-dependent manner. Among them, the triterpenoid saponin compound of Bougainvillea glabra -80 mg / kg dose group significantly reduced the TG content in the liver of DIO mice. After 30 days of administration, the TG content was reduced by 53.8% compared with DIO mice.

[0120] Table 9: Effects of repeated administration of triterpenoid saponins from Bougainvillea glabra on TC and TG in the liver of obese mice

[0121] The pathological sections of the liver (HE staining and oil red staining) are shown in Figure 6. Compared with the WT, the liver cells of the model control group are loose and disorderly arranged, the cytoplasm is reduced and the cells are shrunken, and the tissue contains a large number of lipid droplets. HE staining found that the liver of mice treated with the triterpenoid saponin compound of Bougainvillea glabra was clearly distinguished from the nucleus and cytoplasm of each cell compared with the model control group, the cytoplasm was significantly increased, the cells were more compact and arranged more regularly; Oil red staining found that the liver of mice treated with the triterpenoid saponin compound of Bougainvillea glabra was significantly smaller and the number of lipid droplets was significantly reduced in addition to the nucleus, cytoplasm and cell compactness and arrangement compared with the model control group. This shows that the triterpenoid saponin compound of Bougainvillea glabra can significantly improve the pathological condition of the liver of this model animal.

[0122] discuss

[0123] In summary, the triterpenoid saponin compounds of Bougainvillea var. glabra were administered once daily for multiple doses for 30 days, which significantly reduced the random body weight, body fat percentage, perirenal fat, abdominal fat, and subcutaneous fat of DIO mice, indicating that the triterpenoid saponin compounds of Bougainvillea var. glabra can reduce body weight by reducing the fat content of mice; significantly reduced the liver TG level of DIO mice and improved the pathological condition of liver tissue, indicating that the triterpenoid saponin compounds of Bougainvillea var. glabra can be used to improve non-alcoholic fatty liver (inflammation) / cirrhosis.

[0124] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. Use of a Bougainvillea glabra Choisy triterpenoid saponin compound having the structure of formula (I), characterized in that, For the preparation of a pharmaceutical composition for alleviating or improving obesity, 2. The use according to claim 1, characterized in that, The described pharmaceutical composition is administered to obese individuals.

3. The use according to claim 1, characterized in that, The daily dose of the compound of formula (I) in the pharmaceutical composition is 25 - 600 mg.

4. The use according to claim 1, characterized in that, The described pharmaceutical composition is used to significantly reduce the body fat percentage of obese individuals. The significant reduction means: (body fat percentage of obese individuals without weight loss drugs - body fat percentage of obese individuals after administering weight loss drugs) / body fat percentage of obese individuals without weight loss drugs > 10%, preferably > 20%.

5. The use according to claim 1, characterized in that, The described pharmaceutical composition is used to significantly reduce the weight of adipose tissue in obese individuals. The adipose tissue is selected from the following group: perirenal fat, abdominal fat, subcutaneous fat. And the significant decrease means: (perirenal fat of obese individuals after administering weight loss drugs / body weight) × 100% < 1.7%, (abdominal fat of obese individuals after administering weight loss drugs) / body weight × 100% < 5%, (subcutaneous fat of obese individuals after administering weight loss drugs / body weight) × 100% < 3.4%.

6. The use according to claim 1, wherein The described pharmaceutical composition is used to significantly reduce the liver triglyceride content. The significant reduction means: (triglyceride content of obese individuals without weight loss drugs - triglyceride content of obese individuals after administering weight loss drugs) / triglyceride content of obese individuals without weight loss drugs > 40%, preferably > 50%.

7. A pharmaceutical preparation, characterized in that, The pharmaceutical preparation comprises the compound of formula (I) as described in claim 1 as an active ingredient, and pharmaceutically acceptable excipients, carriers or diluents.

8. Use of a preparation as described in claim 7, characterized in that, For the preparation of weight loss drugs.

9. The use according to claim 8, characterized in that, The weight loss has one or more characteristics selected from the following group: (a) Reduction in body fat percentage; (b) Reduction in adipose tissue content; (c) Reduction in liver triglyceride content; (d) Reduction in body weight; Wherein, the reduction means that the corresponding index of the subject after administering the pharmaceutical composition decreases compared with the subject without administering the pharmaceutical composition, and the difference is significant. The index is selected from the following group: body fat percentage, adipose tissue content, liver triglyceride content, body weight.

10. A method for weight loss, comprising the step of: administering a medically effective amount of the weight loss drug as described in claim 1 or the pharmaceutical preparation as described in claim 7 to a subject in need.

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