A composition for improving metabolic syndrome, its preparation method and application

Abstract

This invention discloses a composition for improving metabolic syndrome, its preparation method, and its application. The composition for improving metabolic syndrome comprises privet fruit, honeysuckle, wolfberry fruit, kudzu root, and astragalus root. The medicinal materials used in the formulation involved in this invention are all traditional Chinese medicinal herbs that are also used in food, exhibiting extremely high safety and definite efficacy. two and db In mice, it demonstrated clear efficacy in lowering blood sugar and improving metabolic syndrome, comparable to metformin, and even superior to metformin in some lipid parameters. Further mechanistic studies showed that the optimized formulation 3 can exert a synergistic effect by regulating multiple metabolic pathways, and can be used to regulate metabolic-related diseases such as diabetes, fatty liver, alcoholic liver disease, and dyslipidemia.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a composition for improving metabolic syndrome, its preparation method, and its application. Background Technology

[0002] The prevalence of obesity continues to rise worldwide. While rapid modernization, urbanization, and socioeconomic growth have contributed to improved living standards, over the past two decades, high stress levels, sedentary lifestyles, and unhealthy eating habits have led to obesity becoming a global epidemic, affecting almost every organ system and threatening human life. Currently, obesity is one of the most common non-communicable diseases, leading to a range of metabolic disorders such as type 2 diabetes and non-alcoholic fatty liver disease (NASH), making it a serious global public health problem.

[0003] The primary cause of obesity is a long-term imbalance between calorie intake and expenditure. Subcutaneous fat is the main storage depot for energy. It is associated with improved metabolism and insulin sensitivity because it comprises brown fat cells containing a large number of mitochondria that play a role in thermogenesis. However, when energy intake is excessive and the storage capacity of subcutaneous fat is depleted, fat accumulates around abdominal visceral organs, such as the liver, leading to non-alcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular disease (ASCVD) in the vascular system, or insulin resistance in muscles.

[0004] Given these complex connections in the pathogenesis of obesity, current treatment options for managing and treating obesity and type 2 diabetes share some similarities, including lifestyle interventions, drug therapy, various newly developed medical devices, and bariatric surgery, all of which are becoming increasingly popular and technologically advanced. Lifestyle interventions are the foundation and first-line treatment for both obesity and type 2 diabetes, with effective obesity management being paramount. Surgical procedures, whether endoscopic or non-endoscopic, have gained acceptance in patients suitable for different methods, but the unavoidable risks and complications of surgery remind us that these techniques are far from perfect. Therefore, for obese individuals who cannot undergo lifestyle interventions, drug control is a relatively low-risk option, and anti-obesity drugs have some anti-diabetic effects. Currently, the most popular research direction in weight-loss drugs is peptide drugs, such as glucagon-like 1 peptide (GLP-1), which is a hot research topic in the weight-loss field for major pharmaceutical companies. It not only slows gastric emptying, increases satiety, and reduces appetite, but also promotes insulin secretion in a glucose-dependent manner. However, because it is a peptide drug, it can only exert its effects through injection, and there is currently a lack of safe and effective oral drugs to improve metabolic diseases.

[0005] Traditional Chinese medicine (TCM) formulas containing both medicinal and edible herbs offer advantages such as definite efficacy and high safety, particularly for the management of chronic diseases like metabolic disorders, sparking a research boom both domestically and internationally. For example, a research team at Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine discovered that Yin Chen Gan Cao Tang (YG) shows great potential in treating metabolic diseases such as NASH. The team was the first to demonstrate that Yin Chen Gan Cao Tang (YG) has a significant therapeutic effect on a mouse model of NASH. They revealed that YG improves NASH symptoms by upregulating farnesol X receptors (FXR), reducing hepatic lipid accumulation, and inhibiting hepatic inflammation and endoplasmic reticulum stress. While Yin Chen Gan Cao Tang is composed of four herbs—Artemisia capillaris, rhubarb, Magnolia officinalis, and licorice—it is not a medicinal and edible herb, limiting its use for long-term management of chronic diseases. Therefore, developing medicinal and edible formulas suitable for the management of chronic metabolic diseases is of significant clinical importance. Summary of the Invention

[0006] The first objective of this invention is to provide a composition for improving metabolic syndrome; the second objective is to provide a method for preparing the composition for improving metabolic syndrome; and the third objective is to provide the application of the composition for improving metabolic syndrome.

[0007] The first objective of this invention is achieved by the composition for improving metabolic syndrome, which consists of privet fruit, honeysuckle, wolfberry, kudzu root and astragalus.

[0008] In this formula, privet fruit is the principal ingredient. Privet fruit is cool in nature, sweet and bitter in taste, and enters the liver and kidney meridians. The *Chinese Pharmacopoeia* records its functions as nourishing the liver and kidneys, improving eyesight, and darkening hair. Modern pharmacological studies have shown that the active ingredients in privet fruit, such as oleanolic acid and privetin, especially the n-butanol phenolic glycoside fraction, can regulate the insulin signaling pathway (involving the IRS-1 / AKT / GSK-3β pathway), intervening in insulin resistance, a core pathological link in metabolic syndrome. Simultaneously, it can inhibit the expression of tissue fibrosis-related factors (such as type I and type III collagen), regulate the aging-associated secretory phenotype (SASP), and intervene in abnormal tissue remodeling related to metabolic syndrome, such as fatty liver fibrosis and muscle atrophy. Therefore, privet fruit is the principal ingredient, treating the root cause of metabolic defects.

[0009] Honeysuckle and wolfberry are used together as assistant herbs. Honeysuckle is cold in nature and sweet in taste, and enters the lung, heart, and stomach meridians. The Chinese Pharmacopoeia states that it clears heat and detoxifies, and disperses wind-heat. Its components, such as chlorogenic acid and luteolin, have anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism-improving effects, effectively addressing chronic low-grade inflammation (metabolic inflammation) that persists during metabolism, thus treating the symptoms. Wolfberry is neutral in nature and sweet in taste, and enters the liver and kidney meridians. The Chinese Pharmacopoeia states that it nourishes the liver and kidneys, and benefits essence and vision. Its components, such as wolfberry polysaccharides and betaine, have antioxidant, anti-inflammatory, pancreatic β-cell-protecting, lipid-regulating, and fatty liver-improving effects, assisting privet fruit in enhancing its ability to nourish liver and kidney yin to strengthen the body's foundation. Honeysuckle clears heat and dispels pathogens, while wolfberry nourishes yin and strengthens the body's resistance. These two herbs, one clearing and one nourishing, work together to help the principal herb regulate disordered glucose and lipid metabolism, ensuring that clearing heat does not harm the body's vital energy, and nourishing yin to aid in functional recovery.

[0010] Kudzu root and astragalus are used together as adjuvant herbs. Kudzu root is cool in nature, sweet and pungent in taste, and enters the spleen, stomach, and lung meridians. The Chinese Pharmacopoeia records its functions as relieving muscle tension and reducing fever, promoting body fluid production and quenching thirst, raising yang and stopping diarrhea, and unblocking meridians and collaterals. Its isoflavone components, such as puerarin and daidzein, can improve insulin sensitivity, promote glucose utilization, regulate blood lipid levels (lowering total cholesterol and triglycerides), and improve microcirculation. This formula utilizes kudzu root's properties of promoting body fluid production and quenching thirst, and raising clear yang to distribute the essence of food and improve the body's utilization of nutrients. Astragalus is slightly warm in nature, sweet in taste, and enters the spleen and lung meridians. The Chinese Pharmacopoeia records its functions as tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing edema, and promoting body fluid production and nourishing blood. Its components, such as astragalus polysaccharides and astragalus saponins, can enhance metabolism, improve insulin resistance, protect vascular endothelium, regulate immunity, and have diuretic effects. This formula utilizes Astragalus membranaceus to invigorate the spleen, replenish qi, and promote diuresis and dampness elimination, thereby enhancing the body's ability to transform and transport fluids and eliminate phlegm and turbidity, targeting the concurrent symptoms of spleen deficiency and dampness obstruction. Kudzu root promotes the upward movement of clear qi and generates fluids to distribute essential nutrients, while Astragalus membranaceus invigorates the spleen, replenishes qi, and transforms dampness and turbidity. Together, these two herbs assist in addressing the common pathogenesis of metabolic syndrome—qi and yin deficiency, spleen deficiency, and dampness obstruction—and help the principal and assistant herbs process pathological products such as dampness and phlegm.

[0011] The formula uses privet fruit as the chief ingredient to nourish the liver and kidneys to address the root cause, intervening in insulin resistance and abnormal tissue remodeling. Honeysuckle and wolfberry are the assistant ingredients, one clearing and the other nourishing, synergistically regulating glucose and lipid metabolism and metabolic inflammatory responses. Kudzu root and astragalus root are the adjuvant ingredients, promoting qi circulation and eliminating dampness to address the symptoms. The formula is meticulously formulated, combining tonification and purgation to treat both the root cause and symptoms. All five ingredients are listed as food-medicine homologous substances by the National Health Commission, ensuring their safety. Through the synergistic effects of nourishing the liver and kidneys, replenishing qi and yin, clearing heat and eliminating turbidity, and promoting blood circulation, the formula regulates multiple metabolic signaling pathways such as AMPK and PPAR-γ, exerting a comprehensive effect in improving insulin resistance, regulating glucose and lipid metabolism, reducing hepatic fat deposition, and alleviating systemic chronic inflammation. As shown in the accompanying diagram, this composition exhibits a clear hypoglycemic effect and improves metabolic syndrome in ob / ob and db / db mouse models. Its hypoglycemic efficacy is comparable to metformin, and its improvement in some lipid indicators is superior to metformin. Liver pathological observations show that the composition's improvement on hepatic steatosis, inflammatory infiltration, and ballooning degeneration is dose-dependent, with the high-dose group showing greater pathological improvement than the metformin group. These experimental data indicate that the effects of the individual herbs in this composition are not simply the sum of their individual effects, but rather a synergistic and comprehensive regulatory effect achieved through specific principal-assistant-adjuvant relationships.

[0012] The second objective of this invention is achieved by including preprocessing, extraction, and postprocessing steps, specifically including: A. Pre-processing: 1) Grind the privet fruit, kudzu root and astragalus root in the formula into powders to obtain privet fruit powder, kudzu root powder and astragalus root powder for later use; 2) Weigh out the honeysuckle and wolfberry according to the recipe and set aside; B. Extraction: The privet fruit powder, kudzu root powder, astragalus powder, honeysuckle and wolfberry were extracted with ethanol solution to obtain privet fruit extract, kudzu root extract, astragalus extract, honeysuckle extract and wolfberry extract, respectively. C. Post-processing: The extracts of privet fruit, kudzu root, astragalus root, honeysuckle, and wolfberry are mixed to obtain a composition for improving metabolic syndrome.

[0013] The third objective of this invention is achieved by using the composition for improving metabolic syndrome in the preparation of medicaments for treating and / or preventing obesity, hyperlipidemia, non-alcoholic fatty liver disease, drug-induced liver injury, and diabetes.

[0014] The formulas involved in this invention use medicinal herbs that are both food and medicine, possessing extremely high safety and definite efficacy. ob and dbIn mice, it demonstrated clear efficacy in lowering blood sugar and improving metabolic syndrome, comparable to metformin, and even superior to metformin in some lipid parameters. Further mechanistic studies showed that the optimized formulation 3 can exert a synergistic effect by regulating multiple metabolic pathways, and can be used to regulate metabolic-related diseases such as diabetes, fatty liver, alcoholic liver disease, and dyslipidemia. Attached Figure Description

[0015] Figure 1 Study on the hypoglycemic activity of different formulations in vivo; Figure 2 Different doses of formulation 3 (100, 200, 400 mg / kg) were administered at... ob / ob Effects of long-term administration to mice on body weight, blood glucose levels, and liver lipid levels; Figure 3 Different doses of formulation 3 (100, 200, 400 mg / kg) were administered at... ob / ob The effects of long-term administration to mice on blood parameters, *P<0.05, **P<0.01, ***P<0.001, compared with... ob / ob Model group comparison; Figure 4 Different doses of formulation 3 (100, 200, 400 mg / kg) were administered at... db / db The effects of long-term administration in mice on body weight, OGTT, and liver lipid levels, *P<0.05, **P<0.01, ***P<0.001, compared with... db / db Model group comparison; Figure 5 Different doses of formulation 3 (100, 200, 400 mg / kg) were administered at... db / db Long-term administration to mice showed its effect on improving fatty liver disease. Figure 6 Different doses of formulation 3 (100, 200, 400 mg / kg) were administered at... db / db The effects of long-term administration to mice on blood parameters, *P<0.05, **P<0.01, ***P<0.001, compared with... db / db Model group comparison; Figure 7 Different doses of formulation 3 (100, 200, 400 mg / kg) were administered at... db / db The effect of long-term drug administration on the expression levels of hepatic lipid metabolism-related genes in mice, *P<0.05, **P<0.01, ***P<0.001, compared with db / db Model group comparison. Detailed Implementation

[0016] The present invention will be further described below with reference to embodiments, but this is not intended to limit the present invention in any way. Any modifications or substitutions made based on the teachings of the present invention shall fall within the protection scope of the present invention.

[0017] The composition for improving metabolic syndrome described in this invention consists of privet fruit, honeysuckle, wolfberry, kudzu root, and astragalus.

[0018] The mass ratio of the privet fruit, honeysuckle, wolfberry, kudzu root and astragalus is (5~15):(5~10):(5~15):(5~15):(5~12).

[0019] The mass ratio of the privet fruit, honeysuckle, wolfberry, kudzu root, and astragalus is 15:10:15:15:12.

[0020] The method for preparing the composition for improving metabolic syndrome according to the present invention includes pretreatment, extraction and posttreatment steps, specifically including: A. Pre-processing: 1) Grind the privet fruit, kudzu root and astragalus root in the formula into powders to obtain privet fruit powder, kudzu root powder and astragalus root powder for later use; 2) Weigh out the honeysuckle and wolfberry according to the recipe and set aside; B. Extraction: The privet fruit powder, kudzu root powder, astragalus powder, honeysuckle and wolfberry were extracted with ethanol solution to obtain privet fruit extract, kudzu root extract, astragalus extract, honeysuckle extract and wolfberry extract, respectively. C. Post-processing: The extracts of privet fruit, kudzu root, astragalus root, honeysuckle, and wolfberry are mixed to obtain a composition for improving metabolic syndrome.

[0021] In step B, the volume percentage concentration of the ethanol solution is 70-90%.

[0022] In step B, the amount of ethanol solution added is based on a material-to-liquid volume ratio of 1:(10~15).

[0023] The extraction described in step B is reflux extraction.

[0024] The reflux extraction time is 1-3 hours.

[0025] The application described in this invention is the use of the composition for improving metabolic syndrome in the preparation of drugs for treating and / or preventing obesity, hyperlipidemia, non-alcoholic fatty liver disease, drug-induced liver injury, and diabetes.

[0026] The invention will be further illustrated below with specific implementation examples: Example 1

[0027] Screening of food and medicine homology formulations Accurately weigh the dried medicinal materials according to the following formulation ratios (Table 1): Ligustrum lucidum (powdered), Lonicera japonica, Lycium barbarum, Pueraria lobata (powdered), and Astragalus membranaceus (powdered). Place them in a 1000mL round-bottom flask and extract them separately by reflux with 80% ethanol for 2 hours, controlling the material-to-liquid ratio at 12 times. After extraction, filter the flask, evaporate the filtrate to recover the ethanol, concentrate it to dryness, and treat the residue under vacuum with an oil pump for 2 hours to obtain the extracts of each formulation.

[0028] Table 1: Screening of Formulas with Both Food and Medicine Properties

[0029] Example 2

[0030] Studies on the hypoglycemic effect of different formulations in vivo use ob / ob The hypoglycemic activity of the extracts from each formulation was screened in mice. Each extract (200 mg / kg) was administered twice daily by gavage for 7 days. After an 8-hour fast, blood was collected from the tail tip of the mice, and the oral glucose tolerance test (OGTT) (3 g / kg glucose) was measured using a glucometer. The results are shown in the attached figure. Figure 1 As shown, the results indicate that privet fruit, honeysuckle, and kudzu root are the main ingredients. When the content is low, the hypoglycemic activity is significantly weakened. The optimal prescription is formulation 3, whose hypoglycemic efficacy is comparable to that of the positive control drug metformin.

[0031] Example 3

[0032] Long-term dosing studies were conducted on different doses of formulation 3. Will ob / ob Mice were randomly divided into groups of six. C57 normal mice served as a control group, receiving a normal basal diet and normal drinking water. After one week of acclimatization, the mice were administered the drug daily via gavage. The C57 normal group and... ob / ob The model control group received 0.5% carboxymethyl cellulose sodium (CMC-Na), while the other treatment groups received different doses of formulation 3 (100, 200, 400 mg / kg) or metformin (200 mg / kg) for 30 days. Body weight, non-fasting blood glucose, and fasting blood glucose were measured regularly. At the end of the experiment, mice were fasted for 12 hours (with free access to water) before sampling. They were anesthetized by intraperitoneal injection of 2% sodium pentobarbital (50 mg / kg), and blood was collected via fundus venous plexus. Mice were euthanized by cervical dislocation, fixed on a mouse table, and the skin, subcutaneous tissue, and peritoneum were sequentially cut along the midline of the abdomen to expose the abdominal cavity. Liver tissue was removed, washed with physiological saline, and then a suitable size of liver tissue from the left lobe was uniformly cut and fixed in a tissue fixation solution. (A 1 × 1 × 0.5 cm sample was taken from the right lobe of the liver, 5 mm from the edge.) 3Large and small liver tissues were fixed in 4% paraformaldehyde for paraffin embedding and HE staining. The remaining tissues were placed in cryovials, sealed in liquid nitrogen, and then stored at -80 °C for later use. Experimental results are attached. Figure 2 and 3 .

[0033] The results showed that formulation 3 had a significant weight-loss effect at high doses and steadily controlled fasting and non-fasting blood glucose levels during treatment. Furthermore, the liver-to-body weight ratio decreased to varying degrees, and total liver cholesterol and triglyceride levels were also reduced, suggesting its effectiveness in reducing weight. ob It may have an ameliorative effect on fatty liver in mice.

[0034] Example 4

[0035] Different doses of formulation 3 in db / db Long-term drug administration studies in mice Will db / db Mice were randomly divided into groups of six. C57 normal mice served as a control group, receiving a normal basal diet and normal drinking water. After one week of acclimatization, the mice were administered the drug daily via gavage. The C57 normal group and... db / db The model control group received 0.5% carboxymethyl cellulose sodium (CMC-Na), while the other treatment groups received different doses of formulation 3 (100, 200, 400 mg / kg) or metformin (200 mg / kg) for 30 days, with regular weight measurements. At the end of the experiment, mice were fasted for 8 hours before sampling (free access to water). Oral glucose tolerance test (OGTT) was performed by tail amputation. Mice were then anesthetized by intraperitoneal injection of 2% sodium pentobarbital (50 mg / kg). Blood was collected via fundus venous plexus sampling. Mice were euthanized by cervical dislocation, fixed on a rat platform, and the skin, subcutaneous tissue, and peritoneum were sequentially cut along the midline of the abdomen to expose the abdominal cavity. Liver tissue was removed, washed with physiological saline, and then a suitable size of liver tissue from the left lobe was uniformly cut and fixed in a tissue fixation solution. (A 1 × 1 × 0.5 cm section was taken from the right lobe of the liver, 5 mm from the edge). 3 Large and small liver tissues were fixed in 4% paraformaldehyde for paraffin embedding and HE staining. The remaining tissues were placed in cryovials, sealed in liquid nitrogen, and then stored at -80 °C for later use. Experimental results are attached. Figures 4-7 .

[0036] use db / db Long-term administration studies of different doses of formulation 3 in mice revealed that formulation 3 had a significant weight-loss effect and, after the treatment ended, significantly dose-dependently improved oral glucose tolerance. Figure 4 In addition, the liver-to-body weight ratio decreased to varying degrees, and liver lipid levels were reduced, suggesting that it also has an ameliorative effect on fatty liver in db mice. Figure 4Hematoxylin and eosin (HE) staining of liver sections showed that the model group exhibited significant hepatic steatosis, inflammatory infiltration, and ballooning degeneration. While the metformin group showed a significant reduction in hepatic steatosis, inflammatory infiltration remained severe. Formula 3, however, dose-dependently reduced hepatic steatosis and inflammatory infiltration, particularly in the high-dose group, where significant improvements in steatosis, inflammatory infiltration, and ballooning degeneration were observed, superior to the metformin group. Figure 5 ).

[0037] In addition, for formula 3 db It significantly improved serum liver function indicators in mice and reduced serum lipid levels in a dose-dependent manner, while having no effect on high-density lipoprotein, suggesting that it has a significant effect on... db It has an ameliorative effect on hyperlipidemia in mice and can protect liver function. Figure 6 Further mechanistic studies have shown that Formulation 3 can synergistically improve metabolic syndrome in multiple ways by improving hepatic triglyceride metabolism, fatty acid oxidation, mitochondrial function and oxidative stress, and inhibiting lipid synthesis. Figure 7 ).

[0038] In summary, the medicinal materials used in the formulations involved in this invention are all traditional Chinese medicinal herbs that are also used as food, possessing extremely high safety and definite efficacy. ob and db In mice, it demonstrated clear efficacy in lowering blood sugar and improving metabolic syndrome, comparable to metformin, and even superior to metformin in some lipid parameters. Further mechanistic studies showed that the optimized formulation 3 can exert a synergistic effect by regulating multiple metabolic pathways, and can be used to regulate metabolic-related diseases such as diabetes, fatty liver, alcoholic liver disease, and dyslipidemia.

Claims

1. A composition for improving metabolic syndrome, characterized in that, The composition for improving metabolic syndrome consists of privet fruit, honeysuckle, wolfberry, kudzu root, and astragalus.

2. The composition for improving metabolic syndrome according to claim 1, characterized in that, The mass ratio of the privet fruit, honeysuckle, wolfberry, kudzu root and astragalus is (5~15):(5~10):(5~15):(5~15):(5~12).

3. A method for preparing the composition for improving metabolic syndrome according to claim 1 or 2, characterized in that, It includes preprocessing, extraction, and postprocessing steps, specifically including: A. Pre-processing: 1) Grind the privet fruit, kudzu root and astragalus root in the formula into powders to obtain privet fruit powder, kudzu root powder and astragalus root powder for later use; 2) Weigh out the honeysuckle and wolfberry according to the recipe and set aside; B. Extraction: The privet fruit powder, kudzu root powder, astragalus powder, honeysuckle and wolfberry were extracted with ethanol solution to obtain privet fruit extract, kudzu root extract, astragalus extract, honeysuckle extract and wolfberry extract, respectively. C. Post-processing: The extracts of privet fruit, kudzu root, astragalus root, honeysuckle, and wolfberry are mixed to obtain a composition for improving metabolic syndrome.

4. The preparation method according to claim 3, characterized in that, In step B, the volume percentage concentration of the ethanol solution is 70-90%.

5. The preparation method according to claim 3, characterized in that, In step B, the amount of ethanol solution added is based on a material-to-liquid volume ratio of 1:(10~15).

6. The preparation method according to claim 3, characterized in that, The extraction described in step B is reflux extraction.

7. The preparation method according to claim 7, characterized in that, The reflux extraction time is 1-3 hours.

8. The use of the composition for improving metabolic syndrome according to claim 1 or 2, characterized in that, The use of the composition for improving metabolic syndrome in the preparation of drugs for treating and / or preventing obesity, hyperlipidemia, non-alcoholic fatty liver disease, drug-induced liver injury, and diabetes.

Images