Natural compound complexing agent for preventing obesity and preparation method thereof

Abstract

The invention discloses a natural compound complexing agent for preventing obesity and a preparation method thereof, and relates to the technical field of health foods and medicines. The natural compound complexing agent is prepared from the following components in parts by weight: 50 to 500 parts of conjugated linoleic acid, 10 to 300 parts of sophocarpidine, 100 to 2000 parts of L-carnitine and 1000 to 10000 parts of apple pectin. According to the invention, a novel efficient weight-losing scheme is researched and developed by screening natural products and excavating medicinal and edible components, the efficiency of intervening the obesity process is improved by virtue of a specific formula combination, and the problems of slow effect and low pertinence in the obesity prevention process caused by various inducements can be avoided by virtue of multi-target and multi-channel adjustment.

Description

Technical Field

[0001] This invention relates to the field of health food and pharmaceutical technology, specifically to a natural compound compound for preventing obesity and its preparation method. Background Technology

[0002] In recent years, with economic and social development, the improvement of people's living standards, and especially changes in lifestyle, while the health of the nation's residents has been continuously improving, the problems of obesity and overweight have become increasingly prominent. Abnormal weight, especially overweight and obesity, is closely related to many diseases and may trigger various chronic diseases such as cardiovascular disease, diabetes, and certain cancers. Therefore, developing a safe and effective weight loss product is of great significance.

[0003] Obesity has multiple causes, and the treatment methods for obesity caused by factors such as body constitution are diverse and vary considerably. Currently, products used for weight loss in the market and clinical practice mainly include Western medicines such as chemically synthesized drugs (e.g., orlistat, smegglutide), meal replacement foods or drinks, and various health supplements. Chemical weight loss drugs have limited applicability and often have contraindications, frequently accompanied by significant side effects such as nausea, diarrhea, or liver and kidney damage. Studies have clearly indicated that using these drugs to treat obesity may lead to weight rebound. Meal replacement foods or drinks have limited effectiveness for weight loss, typically working by increasing satiety to slow food intake, but are characterized by slow results and limited nutritional content. While many natural health supplements have high safety profiles, they suffer from limited weight loss methods, slow effects, and poor stability.

[0004] Existing technology discloses a composition for promoting bowel movements and weight loss. This composition, formulated using various food-grade medicinal ingredients based on the fundamental theories of traditional Chinese medicine, possesses these effects and can be used to treat constipation and obesity. However, its effects are singular, and no specific fat-reducing efficacy is mentioned. Existing technology also discloses a composition with weight-loss effects, its preparation method, and its uses. This composition, made from orlistat and Inonotus obliquus extract, has considerable beneficial effects on reducing weight, decreasing fat accumulation, and inhibiting fat absorption. However, even with the use of natural ingredients, adverse reactions still exist, and its safety remains to be considered.

[0005] Therefore, there is an urgent need for a highly efficient, safe, and stable solution based on natural products in the fields of fat loss, weight reduction, and obesity control. Summary of the Invention

[0006] To address the shortcomings of the aforementioned background technologies, this invention provides a natural compound complex for preventing obesity and its preparation method. This natural compound complex, through natural product screening and the discovery of food-medicine homologous components, develops a novel and highly effective weight loss program. All components of the complex are derived from natural products, avoiding the toxic side effects of chemically synthesized drugs. The natural compound complex described in this invention has wide applications, is easy to store and process, and can be easily formulated into various dosage forms to meet different application and consumer needs. The specific formulation combination of this invention improves the efficiency of intervening in the obesity process. Through multi-target and multi-pathway regulation, it can avoid the problems of slow effectiveness and low targeting in the prevention of obesity caused by multiple inducing factors.

[0007] The first objective of this invention is to provide a natural compound complex for preventing obesity, said natural compound complex comprising the following components in parts by weight: 50-500 parts of conjugated linoleic acid, 10-300 parts of matrine, 100-2000 parts of L-carnitine, and 1000-10000 parts of apple pectin.

[0008] Preferably, the natural compound complex comprises the following components in parts by weight: 100-300 parts conjugated linoleic acid, 50-150 parts matrine, 600-1200 parts L-carnitine, and 3000-7000 parts apple pectin.

[0009] Preferably, the natural compound complex comprises the following components in parts by weight: 200 parts conjugated linoleic acid, 100 parts matrine, 1000 parts L-carnitine, and 5000 parts apple pectin.

[0010] The second objective of this invention is to provide a method for preparing a natural compound complex for preventing obesity, comprising the following steps: Weigh out the conjugated linoleic acid, matrine, L-carnitine and apple pectin according to the weight parts, and mix them thoroughly to obtain a powder mixture; Adding an appropriate amount of physiological saline to the powder mixture and mixing it together produces a gel-like solid mixture, which is a natural compound compound.

[0011] The third objective of this invention is to provide the application of a natural compound complex for preventing obesity in the preparation of an anti-obesity drug.

[0012] Preferably, when preparing the obesity prevention drug, a pharmaceutically acceptable carrier is also added to the natural compound complex.

[0013] Preferably, excipients are also added to the natural compound complex when preparing the obesity prevention drug.

[0014] Preferably, the obesity prevention drug is prepared in the form of capsules, tablets, granules, powders, solutions, or lozenges.

[0015] Compared with the prior art, the beneficial effects of the present invention are: This invention provides a natural compound complex for preventing obesity and its preparation method. Through screening of natural products and mining of food-medicine homologous ingredients, this invention develops a new and highly effective weight loss program. All components of the complex are derived from natural products, avoiding the toxic side effects of chemically synthesized drugs.

[0016] The plant-derived natural product raw materials selected in this invention are safe and stable, and the formulation process is simple, allowing for large-scale, multi-batch, high-throughput preparation through industrial production. The natural compound complex described in this invention exhibits significant effects in obesity-related prevention. It can intervene in glucose and lipid metabolism through multiple pathways and targets, promote intestinal peristalsis, accelerate defecation, and increase satiety through dietary fiber, thereby reducing appetite and delaying eating, thus achieving the effects of intervening in the obesity process and reducing fat and weight.

[0017] The novel natural compound complex provided by this invention employs a completely new formula and a simple preparation process, offering not only remarkable effects but also the ability to continuously intervene in glucose and lipid metabolism. Compared to simple mixtures of single natural components, this complex exhibits a more pronounced fat-reducing effect. Attached Figure Description

[0018] Figure 1 Growth curves for mice in each experimental group; Figure 2 The weight gain of mice in each experimental group; Figure 3 The fasting blood glucose levels of mice in each experimental group; Figure 4 The weight of brown fat; Figure 5 This refers to the weight of perirenal fat. Figure 6 This refers to the weight of groin fat. Figure 7 This refers to the weight of epididymal fat. Figure 8 This represents the total weight of white fat. Figure 9 Brown fat in the Blank group; Figure 10 Brown fat in the HFD group; Figure 11 Brown fat in group T1; Figure 12 Brown fat in group T2; Figure 13 Epididymal fat of the Blank group; Figure 14 Epididymal fat in the HFD group; Figure 15 Epididymal fat of group T1; Figure 16 Epididymal fat of group T2; Figure 17 At the TG level; Figure 18 At the TCHO level; Figure 19 LDL-C level; Figure 20 HDL-C level; Figure 21 Staining the liver in Blank's group; Figure 22 Staining of the liver in the HFD group; Figure 23 Staining of liver tissue in group T1; Figure 24 Staining of liver tissue in group T2; Figure 25 Staining the kidneys in the Blank group; Figure 26 Staining of kidneys in the HFD group; Figure 27 Staining of kidneys in group T1; Figure 28 Staining of kidneys in group T2; Figure 29 ALT / GPT level; Figure 30 At the AST / GOT level; Figure 31 AKP level; Figure 32 UA level; Figure 33 At the CRE level; Figure 34 It is at the BUN level. Detailed Implementation

[0019] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below in conjunction with specific embodiments and accompanying drawings. However, the embodiments described are not intended to limit the present invention.

[0020] The purpose of this invention is to provide a weight-loss compound with few side effects, multiple synergistic effects, and natural raw materials. This compound is a natural compound compound with the effects of preventing obesity and reducing fat; it is mainly used to prepare drugs for preventing obesity.

[0021] To achieve the above objectives, a first aspect of the present invention provides a natural compound complex for preventing obesity, the natural compound complex comprising the following components in parts by weight: Conjugated linoleic acid (CLA) 50-500 parts, matrine 10-300 parts, L-carnitine 100-2000 parts, apple pectin 1000-10000 parts.

[0022] Conjugated linoleic acid (CLA) is one of the essential fatty acids for the human body. It can promote the oxidation and decomposition of fats and the synthesis of human proteins. Studies have reported that CLA can increase the relative abundance of short-chain fatty acid production and reduce obesity induced by high-fat diets by repairing the composition of the gut microbiota in obese rats. It can also significantly increase myoglobin in the human body, improve the ability to store and transport oxygen, and make exercise training more effective.

[0023] Matrine, a natural small molecule, can increase the secretion of GLP-1 by activating intestinal calcium-sensing receptors (CaSRs). GLP-1, as a glucagon-like peptide-1, can enhance satiety, reduce food intake, improve insulin sensitivity, and promote fat oxidation and decomposition, thereby achieving a weight loss effect.

[0024] Apple pectin is an acidic polysaccharide extracted from the cell walls of apples. After absorbing water, it can expand in the stomach to produce a feeling of fullness, reduce appetite, delay gastric emptying, reduce calorie intake and reduce weight, and eliminate food accumulation in the body. As an auxiliary weight loss food, it can promote gastrointestinal motility.

[0025] L-carnitine is an endogenous molecule involved in fatty acid metabolism. Its main function is to transport long-chain fatty acids from outside the mitochondria to inside the mitochondrial membrane, increasing the rate of fatty acid β-oxidation and accelerating the consumption of fat by cells. As a food fortifier, L-carnitine tartrate is its compound source. L-carnitine can accelerate the oxidation of fatty acids for energy, promote the burning of body fat, and improve the body's ability to utilize fat.

[0026] From a fat reduction perspective, conjugated linoleic acid (CLA), as a core component intervening in fat synthesis, can reduce fat accumulation and increase energy expenditure by inhibiting preadipocyte differentiation, activating lipolysis pathways, and inducing thermogenesis in brown adipose tissue. L-carnitine acts as a synergist, promoting fatty acid transport to mitochondria to enhance β-oxidation and improve the metabolic efficiency of free fatty acids. Apple pectin can act as a prebiotic to regulate gut microbiota, strengthen the intestinal barrier, and assist in fat browning, while also slowing down carbohydrate absorption and harmonizing the absorption rates of various components. Matrine has the effect of inhibiting inflammatory pathways, reducing obesity-related chronic inflammation, and improving insulin resistance. As a carrier, apple pectin also has the function of targeted intestinal transport, which can protect the stability of various components and optimize bioavailability. Through multi-target synergy of lipid metabolism regulation, energy transport enhancement, intestinal immunity improvement, and absorption harmonization, these four components can significantly improve fat reduction efficiency and safety.

[0027] The natural compound complex comprises the following components in parts by weight: 100-300 parts conjugated linoleic acid, 50-150 parts matrine, 600-1200 parts L-carnitine, and 3000-7000 parts apple pectin.

[0028] Preferably, the natural compound complex comprises the following components in parts by weight: 200 parts conjugated linoleic acid, 100 parts matrine, 1000 parts L-carnitine, and 5000 parts apple pectin.

[0029] A second aspect of this invention provides a method for preparing a natural compound complex for preventing obesity, comprising the following steps: Weigh out the conjugated linoleic acid, matrine, L-carnitine and apple pectin according to the weight parts, and mix them thoroughly to obtain a powder mixture; Adding an appropriate amount of physiological saline to the powder mixture and mixing it together produces a gel-like solid mixture, which is a natural compound compound.

[0030] An exemplary method for preparing a natural compound complex includes: S1. Weigh out the formulations of each embodiment according to the weight parts and mix them thoroughly to obtain a powder mixture; S2. Mix the above mixture with physiological saline at a volume of 80 mL, stirring while mixing. After mixing, place the mixture in a vortex mixer and vortex to mix evenly, thus preparing a gel-like solid mixture or suspension.

[0031] A third aspect of the present invention provides the application of a natural compound complex for preventing obesity in the preparation of an anti-obesity drug.

[0032] In the preparation of drugs for preventing obesity, a pharmaceutical carrier is also added to this natural compound complex.

[0033] Excipients are also added to this natural compound complex when preparing drugs for preventing obesity.

[0034] In the preparation of drugs for preventing obesity, they are formulated into capsules, tablets, granules, powders, solutions, or lozenges.

[0035] It should be noted that, unless otherwise specified, the experimental methods used in this invention are all conventional methods; and the reagents and materials used, unless otherwise specified, are all commercially available.

[0036] Example 1 A natural compound complex for the prevention of obesity, comprising the following ingredients in parts by weight: CLA conjugated linoleic acid 200mg, matrine 100mg, L-carnitine 1000mg, and apple pectin 5g. The preparation method of this natural compound complex includes the following steps: S1. Weigh out conjugated linoleic acid, matrine, L-carnitine and apple pectin according to the weight parts and mix them thoroughly to obtain a powder mixture; S2. Mix the above mixture with physiological saline at a volume of 80 mL, stirring while mixing. After mixing, place the mixture in a vortex mixer and vortex to mix evenly, thus preparing a gel-like solid mixture.

[0037] Example 2 Similar to Example 1, except that the natural compound complex comprises the following raw materials in parts by weight: 50 mg of CLA conjugated linoleic acid, 10 mg of matrine, 100 mg of L-carnitine, and 1 g of apple pectin.

[0038] Example 3 Similar to Example 1, except that the natural compound complex comprises the following raw materials in parts by weight: 500 mg of CLA conjugated linoleic acid, 300 mg of matrine, 2000 mg of L-carnitine, and 10 g of apple pectin.

[0039] Example 4 Similar to Example 1, except that the natural compound complex comprises the following raw materials in parts by weight: 100 mg of CLA conjugated linoleic acid, 50 mg of matrine, 600 mg of L-carnitine, and 3 g of apple pectin.

[0040] Example 5 Similar to Example 1, except that the natural compound complex comprises the following raw materials in parts by weight: CLA conjugated linoleic acid 300mg, matrine 150mg, L-carnitine 1200mg, and apple pectin 7g.

[0041] Comparative Example 1 A natural compound complex that can intervene in glucose and lipid metabolism, accelerate fat burning, promote bowel movements and reduce appetite. The specific formula is: 100mg proanthocyanidins, 300mg green tea extract (EGCG catechins), 1000mg L-carnitine, and 10g fructooligosaccharides. Proanthocyanidins are polyphenolic compounds that can inhibit key enzymes in fat synthesis, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), by activating AMP-activated protein kinase (AMPK), thereby reducing de novo fatty acid synthesis. They also promote the proliferation of beneficial bacteria such as Bifidobacteria and Akkermansia, inhibit the Firmicutes / Bacteroidetes (F / B) ratio, and reduce energy absorption. Simultaneously, they increase the production of short-chain fatty acids (SCFAs) (such as butyrate), activate intestinal L cells to secrete GLP-1, suppress appetite, and enhance satiety, thus achieving an effect against obesity.

[0042] Catechins, important small molecules in tea, possess antioxidant and free radical scavenging properties, promoting cellular fat metabolism and significantly reducing abdominal fat. Simultaneously, they can significantly inhibit the activity of pancreatic lipase, fatty acid synthase, and hormone-sensitive lipase, reducing fat synthesis and thus inhibiting the proliferation and differentiation of adipocytes. Studies have found that catechin monomers dose-dependently inhibit the differentiation of 3-T3-L1 preadipocytes and reduce triglyceride levels.

[0043] L-carnitine is an endogenous molecule involved in fatty acid metabolism. Its main function is to transport long-chain fatty acids from outside the mitochondria to inside the mitochondrial membrane, increasing the rate of fatty acid β-oxidation and accelerating the consumption of fat by cells. As a food fortifier, L-carnitine tartrate is its compound source. L-carnitine can accelerate the oxidation of fatty acids for energy, promote the burning of body fat, and improve the body's ability to utilize fat.

[0044] Fructose oligosaccharides, a widely used plant prebiotic, can selectively promote the proliferation of beneficial bacteria such as Bifidobacteria and Lactobacillus, inhibit obesity-related flora, and reduce metabolic inflammation caused by endotoxins entering the bloodstream, thereby improving insulin resistance and fat accumulation. The propionic acid and butyric acid (SCFAs) produced by the fermentation of fructooligosaccharides by gut microbiota activate GPR41 / GPR43 receptors, upregulating the secretion of GLP-1 and PYY (peptide YY), suppressing appetite and prolonging satiety. Furthermore, fructooligosaccharides swell after absorbing water, increasing fecal volume, stimulating intestinal peristalsis, softening stool, and helping to regulate bowel movements, thus achieving the effect of weight control.

[0045] From a synergistic perspective, proanthocyanidins and catechins, as core components, reduce adipocyte differentiation, activate HSL, and promote lipolysis by inhibiting fat synthesis targets such as PPAR-γ. Simultaneously, the antioxidant properties of proanthocyanidins can alleviate obesity-related oxidative stress and metabolic inflammation, while catechins can inhibit pancreatic lipase, reducing dietary fat absorption. L-carnitine, as a cotransporter, acts as a CPT1 coenzyme-mediated guide for fatty acids to enter mitochondria, enhancing β-oxidation efficiency and efficiently converting broken-down fat into energy for the body's use, preventing lipotoxic accumulation. Fructooligosaccharides, as an auxiliary harmonizing component, promote the proliferation of beneficial intestinal bacteria to generate SCFAs, assisting in fat browning and strengthening the intestinal barrier to reduce inflammatory interference. They also delay the absorption of carbohydrates and other components, reduce intestinal irritation, and improve bioavailability through intestinal targeting. These four components work together through multiple pathways to enhance weight loss efficiency and safety.

[0046] The method for preparing the natural compound complex provided in Comparative Example 1 includes the following steps: S1. Weigh out 100mg of proanthocyanidins, 300mg of green tea extract (EGCG catechin), 1000mg of L-carnitine, and 10g of oligofructose according to the weight ratio, and mix them thoroughly to obtain a powder mixture. S2. Mix the above mixture with physiological saline at a volume of 80 mL, stirring while mixing. After mixing, place the mixture in a vortex mixer and vortex to mix evenly, thus preparing a gel-like solid mixture.

[0047] To illustrate the natural compound compound provided by the present invention, only Example 1 and Comparative Example 1 are used as examples, and specific experiments are conducted for illustration.

[0048] I. Trial on the effectiveness of intervention in obesity 1. Experimental Materials 1.1 Laboratory Animals Thirty-five healthy C57BL / 6J mice, 5-6 weeks old and weighing 20±2g, were selected and provided by Beijing Vital River Laboratory Animal Co., Ltd., and fed at the School of Life Sciences, Northwestern Polytechnical University. The environment was a clean-grade animal room with a temperature controlled between 22℃ and 25℃ and a humidity of 55±5%. A 12 / 12-hour light / dark cycle was implemented, with light from 7:00 to 19:00. Food and water were provided freely.

[0049] 1.2 Model Establishment Five mice were randomly selected as the blank control group, and the remaining mice were used as the model group to establish a high-fat diet-induced obesity model. The model group was fed a 60% high-fat diet for 8 weeks. Before the experiment, the animals were acclimatized, and their growth and behavior were observed to ensure that the animals were healthy and adapted to the experimental environment.

[0050] 1.3 Grouping and Administration Five mice were randomly selected as a group and divided into different groups: a blank control group (Blank, fed with normal feed) administered saline by gavage according to body weight; a high-fat control group (HFD, fed with high-fat feed) administered saline by gavage according to body weight; and two groups (Comparative Example 1 (T1) and Example 1 (T2)) administered natural products by gavage. The animal experiments strictly adhered to the ethical requirements of the "Regulations on the Management of Experimental Animals" issued by the State Science and Technology Commission of China to ensure the reliability of the experimental results. During animal feeding, the indoor temperature was maintained at 20–26°C, with a daily temperature difference ≤4°C; the relative humidity was maintained at 40–70%, and the light-dark cycle was 12h:12h.

[0051] The animals were administered the drug continuously for 8 weeks, and their weight, food intake, and other indicators were recorded regularly to plot growth curves. At the end of the experiment, the mice were fasted for 12 hours but allowed free access to water, and their fasting blood glucose levels were measured. After euthanizing the mice by cervical dislocation, blood and tissue samples were immediately collected. The complete blood count and related organ and tissue indices of the experimental animals were analyzed. Later, biochemical indicators related to obesity and lipid metabolism were detected, and histopathological observations were performed, including pathological changes in liver and adipose tissue.

[0052] 2 Experimental Results 2.1 Growth curves and weight gain of mice in each experimental group See Figure 1 As shown in the figure, the growth curves of mice in each group during the 8-week gavage process were statistically analyzed. It is clear that at the beginning of the experiment, the body weight of mice in each group was relatively uniform, with no significant difference. With feeding on a 60% high-fat diet and gavage of the experimental groups, a significant difference in body weight appeared between the Blank group and the HFD group, with the Blank group's body weight being significantly lower than that of the HFD group. There was no significant difference in body weight between the T1 experimental group and the HFD group in the body weight curves. However, compared with the HFD group, the T2 experimental group showed a significant and continuous decrease in body weight during the later stages of gavage, with its body weight trending lower than that of the HFD group. This indicates that the T2 experimental group can effectively inhibit the increase in body weight in mice in the HFD model and has an effect against obesity.

[0053] Further calculations of body weight gain in each group of mice, and statistical data, can be found in [reference needed]. Figure 2 As shown, the weight gain in the Blank group was significantly lower than that in the HFD group. The weight gain in the natural product gavage group, Comparative Example 1 (T1) and Example 1 (T2) was also lower than that in the HFD group. Furthermore, the weight gain in the T2 group was closer to that in the Blank group, and its obesity resistance effect was better than that in the T1 and HFD groups.

[0054] Note: Compared with the control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0055] Compared with the model group, #P < 0.05, ##P < 0.01, ###P < 0.001, ###P < 0.0001.

[0056] 2.2 Analysis of routine blood parameters in mice Table 1 and its continuation summarize the blood routine analysis results of mice in each group. The tables show that the HFD group exhibited a decreasing trend in white blood cell count (WBC), lymphocyte count (Lym) and percentage, and monocyte count (Mon) compared to the Blank group. In contrast, the statistical data of the T1 and T2 groups rebounded after drug administration, with the T2 group being closer to the blank control group. Simultaneously, the percentage of neutrophils (Neu) in the HFD group was higher than that in the blank control and both the T1 and T2 groups, with the T2 group showing better results than the T1 group. These results suggest that obesity in the HFD group mice may cause a long-term chronic low-grade inflammatory response, thereby affecting the generation, distribution, and function of immune cells. The most obvious characteristic of obesity is fat accumulation, and the release of inflammatory factors during adipogenesis promotes the generation and release of neutrophils, leading to the inhibition of immune cell differentiation. The results in the table further demonstrate that obesity affects the immune system, showing a compensatory increase in neutrophils and a decreasing trend in the number of other immune cells, ultimately reflected in the blood routine indicators.

[0057] Meanwhile, observations in the table show that, except for the Blank group, all other high-fat diet-fed experimental groups exhibited a decrease in mean corpuscular volume (MCV). At the data level, groups T1 and T2 showed a slight recovery, with group T2 being closer to the blank control group. These results suggest that obesity may also cause abnormal iron metabolism or nutritional imbalances. Analysis suggests that the chronic inflammatory response often associated with obesity leads to elevated levels of hepcidin in the body, inhibiting intestinal iron absorption and resulting in abnormal nutrient absorption.

[0058] In addition, all four experimental groups showed an increase in mean globulin concentration (MCHC). The general increase was mainly related to red blood cell dehydration and blood concentration during sample processing, and did not reflect pathological changes.

[0059] Table 1. Blood routine analysis results of mice in each experimental group

[0060] Continued from Table 1-1

[0061] Continued from Table 1-2

[0062] It should be noted that Tables 1-1 and 1-2 are supplementary test results for the remaining indicators of the blood routine data in Table 1.

[0063] 2.3 Fasting blood glucose in mice See Figure 3As shown, the fasting blood glucose levels of mice after 12 hours of fasting with unlimited water are displayed. Combined with data analysis, it was found that the fasting blood glucose level of the HFD group was slightly lower than that of the Blank group. After T1 and T2 gavage treatments, the blood glucose level of the T2 group increased and was significantly higher than that of the HFD group.

[0064] Obesity induced by a high-fat diet leads to insulin resistance, causing the animal to secrete more insulin as compensation. This excess insulin continuously promotes glucose uptake and utilization by peripheral tissues while inhibiting hepatic gluconeogenesis, resulting in lower blood glucose levels. This manifests as an over-regulation to alleviate insulin resistance, leading to hypoglycemia. Furthermore, blood glucose was measured during the later stages of fasting. The HFD group, with sufficient fat reserves, could maintain metabolism through fat energy, and glucose was not replenished promptly after consumption, resulting in lower than normal blood glucose levels. In contrast, the T2 group regulated the compensatory mechanism against insulin resistance caused by obesity, showing a significantly higher blood glucose level than the HFD group. Blood glucose recovered from the lower levels of the HFD group to a range closer to normal, further indirectly reflecting the improvement in insulin resistance.

[0065] 2.4 Mouse organ index Table 2 shows that the heart, liver, spleen, lung, and kidney indices in the HFD group were all lower than those in the Blank group. Among them, the multi-organ indices were lower than those in the T1 and T2 groups, and the epididymal fat index was significantly higher than that in the Blank group and the T1 and T2 groups, with significant differences.

[0066] The organ index (calculated as "organ weight / body weight × 100%)" is a commonly used indicator reflecting the relative developmental status or function of organs. The decreased multi-organ index in the HFD group indicates that the impact of a high-fat diet on organs exceeds the rate of weight gain, suggesting relative organ atrophy, which can lead to abnormal functional load and structural damage. Table 2 demonstrates that a high-fat diet causes damaging effects on multiple organs, while groups T1 and T2 can mitigate high-fat damage and play a certain protective and repairing role in organ structure and function.

[0067] Table 2 Organ index of mice in each experimental group

[0068] Note: Compared with the control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0069] Compared with the model group, #P < 0.05, ##P < 0.01, ###P < 0.001, ###P < 0.0001.

[0070] 2.5 Fat weight in each group of mice.

[0071] See Figures 4-8It can be seen that, except for the brown adipose tissue which showed no significant difference among the groups, the changes in the other white adipose tissue groups were very regular and showed similar trends. The HFD group was significantly higher than the Blank group, while the T1 and T2 groups showed a decreasing trend in that order and were both lower than the HFD control group. The fat reduction trend in the T2 group was more obvious, indicating that it has a good effect on improving fat accumulation caused by a high-fat diet and has a certain resistance effect on fat accumulation in obese mice, with obvious effects.

[0072] Note: Compared with the control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0073] Compared with the model group, #P < 0.05, ##P < 0.01, ###P < 0.001, ###P < 0.0001.

[0074] 2.6 HE staining of brown adipose tissue and epididymal fat in mice (20X) See Figures 9-12 The results of HE staining of brown adipose tissue in each experimental group at 20X are shown. As can be seen from the figure, the Blank group exhibits the structural characteristics of typical brown adipose tissue: the cells are mainly composed of multilocular lipid droplets, which are small in size, uniform in size, and diffusely vacuolated; the cell nuclei are regular in shape (round / elliptical), mostly centered or slightly off-center; the interstitial structure is clear, and the cells are arranged in an orderly manner.

[0075] Compared with the CK group, the HFD group showed a significant trend towards lipid droplet monochasmization, with a substantial increase in droplet volume and size heterogeneity, and the formation of large lipid droplet aggregation foci in some areas. Cell nuclei were compressed and deformed, and their positions were significantly displaced; the interstitial structure was disrupted, and the cells were loosely arranged.

[0076] Compared with the HFD group, the T1 group showed improved lipid droplet morphology, significantly reduced lipid droplet volume, increased proportion of multilocular lipid droplets, and improved size uniformity; the cell nuclei were more regular in shape and more centrally located; the degree of interstitial disorder was reduced, but a small number of structural abnormalities remained, and the interstitial tissue was slightly loose.

[0077] The T2 group showed lipid droplet multilocularization characteristics similar to Blank, with uniform size and diffuse distribution; cells and stroma were normalized, cell nuclei were regular and evenly distributed, and stroma structure was intact; indicating that T2 intervention is more efficient in repairing HFD-induced brown adipose tissue morphological damage, and is superior to T1 in reversing lipid droplet monolocularization and restoring cell and stroma structure.

[0078] See Figures 13-16The results of HE staining of epididymal fat in each experimental group at 20X are shown. As can be seen from the figure, in the Blank group, adipocytes were uniform in size, nearly round in shape, and regularly distributed; the nuclei were uniformly attached to the cell membrane, the interstitium was extremely sparse, and there was no proliferation or inflammatory infiltration. Adipocyte vacuoles were clearly visible, and the cell membranes were intact; the nuclei were flattened and uniformly stained; the intercellular connections were tight, with no size differences or morphological distortion.

[0079] Compared to the Blank group, the HFD group showed significant heterogeneity in adipocyte size (mast cells were present) and irregular morphology; pink fibrous / vascular proliferation in the interstitium disrupted tissue homogeneity. Mast cell vacuolar expansion was more pronounced, and cell membrane tension increased; some cell nuclei deviated from their adherent positions, and even multinucleated aggregation occurred; the number of purplish-blue cells (suspected immune cells) in the interstitium increased.

[0080] Compared with the HFD group, the adipocytes in the T1 group were nearly round in shape, with good uniformity in size and regular distribution; the interstitial components were extremely sparse, with no obvious proliferation or inflammatory accumulation. The adipocyte vacuoles were clear, and the cell membranes were intact; the nuclei were flattened and round, stained uniformly, and stably attached to the cell membrane; the intercellular connections were tight, with no size differences or morphological distortion.

[0081] In the T2 group, the adipocytes showed slightly increased heterogeneity in size and were more oval in shape; the distribution of pink fibers and blood vessels in the stroma was slightly disordered, with localized increased density, but not significantly. Some adipocytes showed more significant vacuolar expansion and increased cell membrane tension; a very small number of cell nuclei deviated from their adherent positions, but the overall effect was still better than that of the HFD group, improving obesity caused by high fat intake.

[0082] 2.7 Levels of four lipid parameters in mouse blood See Figures 17-20 The results of four lipid tests are shown for each experimental group. As can be seen from the figure, in the tests of total cholesterol (TG) and triglycerides (T-CHO), the HFD model group was significantly higher than the Blank control group; in the tests of high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), there were no significant differences in the data of multiple groups.

[0083] Furthermore, the T2 experimental group showed lower levels of both TG and LDL-C compared to the HFD group. This indicates that the high-fat diet successfully established an obesity-related lipid metabolism disorder model, and the intervention in the T2 experimental group effectively reversed the abnormal lipid profile, demonstrating its role in improving obesity-related lipid metabolism disorders.

[0084] 2.8 HE staining of mouse liver and kidney See Figures 21-24 The results of HE staining of the liver in each experimental group at 20X are shown. As can be seen from the figure, the Blank group had normal tissue structure, clear liver lobule structure, polygonal and uniform hepatocytes, and abundant pink granular cytoplasm. No obvious inflammatory cell infiltration, hepatocyte necrosis, fatty degeneration, or fibrosis was observed in the liver lobules or portal area.

[0085] Compared to the Blank group, the HFD group showed significant hepatocyte steatosis in liver tissue, with round vacuoles of varying sizes (lipid droplets) appearing in the cytoplasm. Hepatocytes also exhibited hydropic degeneration and swelling. Nucleus fragmentation and dissolution, focal hepatocyte necrosis, and scattered inflammatory cell infiltration were observed.

[0086] Compared with the HFD group, the T1 group showed patches of round lipid droplets distributed in the liver tissue, accompanied by focal necrosis of hepatocytes and obvious inflammatory infiltration.

[0087] The tissue structure of group T2 was normal, with no obvious abnormalities. The hepatocytes were polygonal, uniform in size, and had abundant pink granular cytoplasm. No obvious inflammatory cell infiltration, hepatocyte necrosis, or fatty degeneration was observed in the hepatic lobules and portal areas. It can be seen that group T2 can improve the pathological changes in liver tissue caused by fatty degeneration and reduce the inflammatory response. At the same time, the formula does not cause significant pathological damage to the animal liver.

[0088] See Figures 25-28 The results of HE staining of the kidneys in each experimental group at 20X are shown. As can be seen from the figure, in the Blank group, lymphocytes in the white pulp were densely clustered, with round and deeply stained nuclei, consistent with the morphology of mature lymphocytes, and with a low nucleocytoplasmic ratio; the distribution of red pulp sinusoids and macrophages was normal, with no significant inflammatory infiltration or structural damage, and the immune microenvironment was in good homeostasis.

[0089] Compared with the Blank group, the HFD group showed a decrease in white pulp lymphocyte density, and although the nuclei remained round, they were loosely arranged; the red pulp cells showed heterogeneity, and suspected inflammatory cell infiltration was observed, indicating an abnormal immune response.

[0090] Compared with the HFD group, the T1 group showed decreased lymphocyte density in the white pulp, loose arrangement, and light staining, suggesting abnormal cell activation or proliferation; the red pulp interstitium was widened, the blood sinusoids were distorted, and cellular heterogeneity was increased.

[0091] In the T2 group, lymphocytes were densely clustered in the white pulp, with round and deeply stained nuclei, consistent with the morphology of mature lymphocytes, and a low nucleocytoplasmic ratio. The red pulp structure was loose but orderly, with normal distribution of blood sinuses and macrophages, and no obvious inflammatory infiltration or interstitial destruction. This suggests that the T2 group will not cause significant pathological damage to the kidneys of animals, and at the same time improve the pathological kidney damage caused by high lipids.

[0092] 2.9 Evaluation of Liver Function in Mice Alkaline phosphatase (AKP) is mainly found in the bile duct membrane of hepatocytes. When the bile duct is obstructed, AKP excretion is hindered, and its activity in the blood increases. (The normal serum level in C57 mice aged 8-24 weeks is approximately 4.5-12 King's units / 100mL). ALT (alanine aminotransferase) is mainly found in the cytoplasm of hepatocytes, and elevated levels are commonly seen in liver diseases such as viral hepatitis, drug-induced liver injury, and fatty liver (normal levels are approximately 10-40 U / L). Aspartate aminotransferase (AST) is mainly found in the mitochondria of hepatocytes. When hepatocytes are severely damaged, mitochondria rupture, releasing AST into the blood. Therefore, elevated AST usually indicates severe hepatocyte damage (normal levels are approximately 35-100 U / L).

[0093] See Figures 29-31 The results showed that the levels of AKP, ALT, and AST in each group were basically within the normal range, while the ALT level in the HFD group was low. The decrease in serum AST in mice usually had no clear pathological significance. The above data suggest that the drug had no significant effect on liver function.

[0094] 2.10 Evaluation of mouse renal function BUN (blood urea nitrogen) reflects the kidney's excretory function; elevated CRE (creatinine) more directly indicates a decrease in glomerular filtration rate (impaired kidney excretory function); elevated UA (uric acid) mainly indicates abnormal purine metabolism or kidney excretory dysfunction (such as increased uric acid reabsorption due to renal tubular damage).

[0095] See Figures 32-34 The results showed no significant differences in BUN and CRE values ​​among the groups. The normal range for UA was approximately 8-30 μL, but diagnostic conclusions require analysis of the trends in blood urea nitrogen and creatinine. Mild fluctuations in UA alone are usually not significant. The UA value in the blank control sample was far >50 μmol / L, which may be related to hemolysis, leading to a false increase in UA. This is because red blood cells contain a large amount of purine metabolic intermediates. All the above data suggest that the drug effects in each experimental group had no significant impact on renal function.

[0096] Although embodiments of the present invention have been shown and described above, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A natural compound complex for preventing obesity, characterized in that, The natural compound complex comprises the following components in parts by weight: 50-500 parts of conjugated linoleic acid, 10-300 parts of matrine, 100-2000 parts of L-carnitine, and 1000-10000 parts of apple pectin.

2. The natural compound complex for preventing obesity according to claim 1, characterized in that, The natural compound complex comprises the following components in parts by weight: 100-300 parts conjugated linoleic acid, 50-150 parts matrine, 600-1200 parts L-carnitine, and 3000-7000 parts apple pectin.

3. The natural compound complex for preventing obesity according to claim 1, characterized in that, The natural compound complex comprises the following components in parts by weight: 200 parts conjugated linoleic acid, 100 parts matrine, 1000 parts L-carnitine, and 5000 parts apple pectin.

4. A method for preparing a natural compound complex for preventing obesity as described in any one of claims 1 to 3, characterized in that, Includes the following steps: Weigh out the conjugated linoleic acid, matrine, L-carnitine and apple pectin according to the weight parts, and mix them thoroughly to obtain a powder mixture; Adding an appropriate amount of physiological saline to the powder mixture and mixing it together produces a gel-like solid mixture, which is a natural compound compound.

5. The use of the natural compound complex for preventing obesity as described in any one of claims 1 to 3 in the preparation of an anti-obesity drug.

6. The application according to claim 5, characterized in that, In the preparation of drugs for preventing obesity, a pharmaceutically acceptable carrier is also added to this natural compound complex.

7. The application according to claim 5, characterized in that, Excipients are also added to this natural compound complex when preparing drugs for preventing obesity.

8. The application according to claim 5, characterized in that, In the preparation of drugs for preventing obesity, they are formulated into capsules, tablets, granules, powders, solutions, or lozenges.

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