Compound cypress-astragalus pill and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a compound cypress-astragalus pill and application thereof. The compound cypress and radix astragali pill is prepared from the following components in parts by mass: 10 to 25 parts of cortex phellodendri, 40 to 80 parts of radix hedysari, 20 to 40 parts of radix rehmanniae and 10 to 30 parts of folium crataegi. The compound cypress-stilbene pill takes radix hedysari as a monarch drug to tonify qi, promote urination, nourish yin and promote salivation, the radix rehmanniae is matched to clear heat, cool blood, nourish yin and promote salivation, the golden cypress is used to clear heat, dry dampness, purge fire and remove steam, so that the heat-clearing and yin-nourishing effects are more prominent, the hawthorn leaves for regulating qi, activating blood, dispersing blood stasis, dredging collaterals, dissolving turbidity and reducing lipid are used, and the medicines are used in compatibility to achieve the effects of clearing heat, resolving dampness, removing blood stasis and reducing phlegm. The traditional Chinese medicine composition can effectively relieve symptoms of patients with glucolipid metabolism syndromes, and the purpose of treating both symptoms and root causes is achieved.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a compound Baiqi pill and its application. Background Technology

[0002] Metabolic syndrome (MS) is a pathological state characterized by insulin resistance and encompassing multiple metabolic disorders, including those affecting blood pressure, blood glucose, and blood lipids. Because severe disturbances and interactions between glucose and lipid metabolism are the core pathological processes of MS, the concept of "glucose-lipid metabolism syndrome" more accurately encapsulates its essence and has become a current research hotspot in metabolic diseases. Epidemiological data shows that the global prevalence of glucose-lipid metabolism syndrome is an average of 31%, and it is projected to increase to 53% by 2035. Its clinical manifestations mainly include central obesity, hyperglycemia, hypertension, and hypertriglyceridemia, significantly exacerbating the development of type 2 diabetes, non-alcoholic fatty liver disease, and atherosclerosis, characterized by high morbidity, high disability rate, and high mortality rate. Currently, clinical treatment for glucose-lipid metabolism syndrome primarily employs a strategy based on lifestyle interventions (dietary control and increased exercise), combined with hypoglycemic and lipid-regulating drugs such as metformin and atorvastatin. However, in the field of traditional Chinese medicine, although research has confirmed that natural active ingredients such as matrine and aloe anthraquinone have good hypoglycemic and lipid-regulating effects, these ingredients are currently mostly still in the research stage and have not yet been successfully developed into mature Chinese medicine preparations and applied in clinical practice.

[0003] The information disclosed in this background section is intended only to enhance the understanding of the overall background of the invention and should not be construed as an admission or in any way implying that the information constitutes prior art known to those skilled in the art. Summary of the Invention

[0004] The purpose of this invention is to provide a compound cypress and astragalus pill and its application.

[0005] To achieve the above objectives, the present invention provides the following technical solution: A compound cypress and astragalus pill, by weight, is prepared from the following ingredients: 10-25 parts of phellodendron bark, 40-80 parts of red astragalus root, 20-40 parts of rehmannia root, and 10-30 parts of hawthorn leaf.

[0006] Furthermore, by weight, the Compound Baiqi Pill is prepared from the following ingredients: 20 parts of Phellodendron bark, 60 parts of Astragalus root, 30 parts of Rehmannia root, and 20 parts of hawthorn leaf.

[0007] This invention also provides a method for preparing the compound Baiqi pill, comprising the following steps: S1. Take two-thirds of the medicinal materials in 310 times the prescription amount, add 12 times the weight of water and decoct 3 times, 1 hour each time. Combine the filtrates, filter, concentrate under reduced pressure, and spray dry to obtain dry extract powder. S2. Take the remaining amount of the prescribed medicinal materials, dry them, pulverize them, and pass them through a 100-mesh sieve to obtain fine powder; S3. Mix the dry powder obtained in S1 with the fine powder obtained in S2, add 60% ethanol, make into pills by molding method, and dry at 60℃ for 8 hours to obtain the compound Baiqi pills.

[0008] The present invention also provides the application of the aforementioned Compound Baiqi Pill in the preparation of a drug for treating glucose and lipid metabolism syndrome.

[0009] This invention also provides the application of the aforementioned Compound Baiqi Pill in the preparation of drugs that lower triglyceride (TG) and aspartate aminotransferase (AST).

[0010] The present invention also provides the application of the aforementioned Compound Baiqi Pill in the preparation of drugs that improve alanine aminotransferase (ALT).

[0011] This invention also provides the application of the aforementioned Compound Baiqi Pill in the preparation of drugs for regulating total cholesterol (TC).

[0012] Compared with the prior art, the present invention has the following beneficial effects: This invention, Compound Baiqi Pill, uses Astragalus membranaceus as the principal ingredient, which tonifies Qi, promotes diuresis, nourishes Yin, and generates fluids. It is combined with Rehmannia glutinosa to clear heat, cool the blood, nourish Yin, and generate fluids, and Phellodendron chinense to clear heat, dry dampness, purge fire, and eliminate steaming heat, making the effects of clearing heat and nourishing Yin more prominent. Hawthorn leaves are also used to regulate Qi, activate blood circulation, remove blood stasis, clear the meridians, and reduce turbidity and lipids. The combination of these drugs achieves the effects of clearing heat and removing dampness, removing blood stasis and resolving phlegm, and tonifying Qi and nourishing Yin. It can effectively relieve the symptoms of patients with diabetes and lipid metabolism syndrome and achieve the goal of treating both the symptoms and the root cause. Attached Figure Description

[0013] Figure 1 For modeling and drug administration protocols; Figure 2 Network pharmacology analysis of the compound Baiqi pill for treating glucose and lipid metabolism syndrome of this invention; Figure 3 The effects of the compound Baiqi pill of the present invention on body weight (A), fasting blood glucose (B), oral glucose tolerance (C), food intake (D), water intake (E) and urine output (F) of rats with glucose and lipid metabolism syndrome; Figure 4 The effects of the compound Baiqi pill of the present invention on TC (A), TG (B), liver index (C), ALT (D) and AST (E) in rats with glucose and lipid metabolism syndrome; Figure 5 The effects of the compound Baiqi pill of the present invention on the content of SOD (A), GSH (B) and MDA (C) in the liver of rats with glucose and lipid metabolism syndrome; Figure 6 Improvement effect of the compound Baqi Pills of the present invention on pancreatic injury (A), liver injury (B) and liver lipid deposition (C) in rats with glycolipid metabolism syndrome (200 ×); Figure 7 Effect of the compound Baqi Pills of the present invention on increasing the protein expression of PI3K / AKT pathway in the liver of rats with glycolipid metabolism syndrome (400 ×); Figure 8 Effect of the compound Baqi Pills of the present invention on the mRNA expression of liver inflammatory factors (A) and PI3K / AKT pathway (B) in rats with glycolipid metabolism syndrome.

[0014] Explanation of main reference numerals: Figure 2 Among them: A - Venn diagram of the component targets of the compound Baqi Pills and the disease targets of glycolipid metabolism syndrome; B - "drug - component - target" network diagram of the compound Baqi Pills; C - KEGG pathway diagram of the compound Baqi Pills in the treatment of glycolipid metabolism syndrome; Figure 3-8 Among them, Control: blank group; Model: model group; FFBQ - L: low - dose group of compound Baqi Pills; FFBQ - M: medium - dose group of compound Baqi Pills; FFBQ - H: high - dose group of compound Baqi Pills; XZK: Xuezhikang group; Metformin: metformin group. Compared with the Control group, * P < 0.05, ** P < 0.01; compared with the Model group, # P < 0.05, ## P < 0.01. Detailed implementation manners

[0015] The technical solutions of the present invention patent will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0016] 1. Materials 1.1 Experimental animals 50 SPF - level male SD rats with a body weight of 200 g ± 20 g were provided by Chengdu Dashuo Experimental Animal Co., Ltd. (license number SCXK (Chuan) 2020 - 0030). This study was approved by the Experimental Animal Ethics Committee of Shaanxi University of Chinese Medicine (SUCMDL20250305028).

[0017] 1.2 Preparation of Compound Baiqi Pill Compound Baiqi Pill Formula: 20g of Phellodendron bark, 60g of Astragalus root, 30g of Rehmannia root, and 20g of Crataegus leaf.

[0018] Take two-thirds of the prescribed amount of medicinal materials (310 times the weight), add 12 times the weight of water, and decoct three times for 60 minutes each time. Combine the filtrates, filter, concentrate under reduced pressure, and spray dry to obtain a dry extract powder. Take the remaining one-third of the prescribed amount of medicinal materials, dry, pulverize, and pass through a 100-mesh sieve to obtain a fine powder. Mix the dry extract powder and the fine powder evenly, add 60% ethanol, and form into pills using a plastic molding method at a stirring speed of 30 rpm and a pill-forming speed of 35 rpm. Place the pills in a forced-air drying oven at 60℃ for 8 hours, package them, and each bag contains 6g to obtain the finished Compound Baiqi Pills.

[0019] 1.3 Experimental Drugs and Reagents Metformin Hydrochloride Tablets (Shanghai Shourusong Pharmaceutical Co., Ltd., batch number 240927); Xuezhikang Capsules (Beijing Beida Weixin Biotechnology Co., Ltd., batch number 20230255); Streptozotocin (STZ, Shanghai Ruji Biotechnology Development Co., Ltd., batch number 241020); Sodium citrate buffer solution (Beijing Solarbio Science & Technology Co., Ltd., batch number 240009007w); Total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) assay kits (Nanjing Jiancheng Bioengineering Institute, batch numbers 20241202, 20241204, 20250423, 20250424, 20250509, 20250512, 20250509, 20250517, 20250506 respectively); Animal Total RNA Isolation Kit, RT Easy TM II. Real-Time PCR Easy TM -SYBR Green I (Chengdu Fuji Biotechnology Co., Ltd., batch numbers are R250301, 250201, and 250301 respectively); P-PI3K antibody, P-AKT antibody, and P-FOXO1 antibody (Shenyang Wanlei Biotechnology Co., Ltd., batch numbers U05270482, U04180352, and U07253956, respectively).

[0020] 1.4 Experimental Apparatus BSA124S electronic balance (Sartorius Scientific Instruments (Beijing) Co., Ltd.); Accu-Chek Guide blood glucose meter (Roche Blood Glucose Health Care Company); KDC-160HR High-Speed ​​Refrigerated Centrifuge (Zhongjia Branch of Keda Innovation Co., Ltd.); JXFSTPRP-24L Fully Automatic Rapid Sample Grinding Instrument (Shanghai Jingxin Industrial Development Co., Ltd.); Epoch2 full-wavelength microplate reader (Gene Technology Co., Ltd.); K5800 Ultra-Micro Spectrophotometer (Beijing Kai'ao Technology Development Co., Ltd.); TC 96 / G / H(b)C type gene amplification instrument (Hangzhou Borui Technology Co., Ltd.); A40425 Real-Time PCR Instrument (Thermo Fisher Scientific).

[0021] 2 Methods 2.1 Network pharmacology analysis The active ingredients "Phellodendron bark", "Rehmannia root", "Astragalus root", and "Crataegus leaf" were searched using the TCMSP (www.tcmsp-e.com) database to screen for active ingredients with an oral bioavailability (OB) ≥ 30% and a drug-likeness ratio (DL) ≥ 0.18. ] SwissTargetPrediction (http: / / www.swisstargetPrediction.ch / ) was used to predict the active ingredient targets of drugs. The keyword "Glucose and lipid metabolism syndrome" was searched in the GeneCards (https: / / www.genecards.org / ) and OMIM (https: / / www.omim.org / ) databases to screen for disease-related targets. The Venny 2.1 (https: / / www.bioinformatics.com.cn / ) online tool was used to screen for the intersection of drug targets and disease targets, and a "Traditional Chinese Medicine-Ingredient-Target" network was constructed using Cytoscape 3.9.1 software. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the intersection targets using the DAVID database (https: / / davidbioinformatics.nih.gov / ), and the analysis results were visualized using the MicroBioInformatics platform (http: / / www.bioinformatics.com.cn / ).

[0022] 2.2 Model Preparation and Grouping Scheme After one week of acclimatization feeding, 6 SD rats were randomly selected as the control group, and the rest as the model group. The control group was fed a normal diet, while the model group was fed a high-sugar, high-fat diet (59% basal diet, 18% lard, 20% sugar, and 3% egg yolk). After 12 weeks of continuous feeding, all animals were fasted but allowed free water for 12 hours. The rats in the model group were given 30 mg / kg of food according to their body weight. -1 Rats in the control group were injected intraperitoneally with 1% streptozotocin (STZ), while rats in the control group were injected with an equal volume of sodium citrate buffer. Fasting blood glucose was measured by blood collection from the tail vein on day 4 post-intraperitoneal injection; a blood glucose concentration ≥16.7 mmol / L was required. -1 A model of diabetes was successfully established. Eight rats died during the modeling process, and 36 rats successfully developed the model.

[0023] The dosage was calculated by converting the drug equivalent dose for humans and rats using a body surface area conversion factor. The conversion method was 6.3 times the dose for a 70 kg adult. Grouping and administration details are as follows: Control group n = 6), Model Group (Model, n = 6), Compound Baiqi Pill low-dose group (FFBQ-L, n = 6, 0.945 g·kg -1 Compound Baiqi Pills medium-dose group (FFBQ-M) n = 6, 1.89 g·kg -1 Compound Baiqi Pills high-dose group (FFBQ-H) n = 6, 3.78 g·kg -1 ), Xuezhikang group (XZK, n = 6, 0.108 g·kg -1 Metformin group, n = 6, 0.2 g·kg -1 ).

[0024] Each group was administered the corresponding drug, while the Control and Model groups received an equal volume of physiological saline. The intervention was performed via gavage for 6 consecutive weeks, once daily. Rat body weight and fasting blood glucose levels were recorded at fixed times weekly. The modeling and drug administration regimens are detailed below. Figure 1 .

[0025] 2.3 Oral glucose tolerance test Five weeks after administration, oral glucose tolerance (OTGG) tests were performed. Rats in each group were fasted for 12 hours but allowed free access to water, and then administered 2 g / kg of oral glucose tolerance test by gavage according to their body weight. -1 A 50% glucose solution was prepared, and blood glucose levels were measured at 0, 30, 60, 90, and 120 min.

[0026] 2.4 Sample Collection Before sampling, all rats were placed in individual metabolic cages and given free access to food and water. Food intake, water intake, and urine output were recorded over 24 hours, and a portion of urine was collected. After the last administration, rats in each group were fasted for 12 hours, and their body weight was recorded. After anesthesia with isoflurane, blood was collected from the abdominal aorta. After the blood samples were allowed to stand for 30 minutes, they were then sampled at 3500 r·min. -1 Serum was obtained by centrifugation for 10 min, aliquoted, and stored at -80℃ for later use. Pancreas and liver were collected from rats in each group. The left lobe of the pancreas and liver was fixed in 4% paraformaldehyde, and the remaining liver was rapidly frozen in liquid nitrogen and then stored at -80℃ for later use.

[0027] 2.5 Detection of organ indices and biochemical indicators Remove the liver and its capsule, blot the blood with filter paper, weigh it, and calculate the liver index (%) = liver weight / body weight × 100%. ] .

[0028] Follow the kit instructions to measure the levels of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in serum; and measure the levels of superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) in the liver.

[0029] 2.6 HE staining for pathological changes in pancreas and liver tissues Pancreatic and liver tissues fixed with paraformaldehyde were dehydrated, cleared, and embedded in paraffin using a graded series of ethanol solutions before being sectioned. Sections were dewaxed, stained with hematoxylin for 5-7 min, differentiated with 1% hydrochloric acid ethanol for 2-5 s, and stained with water-soluble eosin for 2 min. They were then dehydrated with anhydrous ethanol, cleared with xylene, air-dried, and mounted with neutral resin. The pathological morphology of the liver tissue was observed under a light microscope.

[0030] 2.7 Detection of pathological changes in liver tissue using Oil Red O staining Fresh liver tissue was collected, fixed with 4% paraformaldehyde, embedded in OCT embedding medium, frozen sectioned, stained with Oil Red O in the dark for 10 min, moderately differentiated with 75% ethanol, washed with water to remove excess dye, counterstained with hematoxylin for 3-5 min, mounted with glycerol gelatin and preserved, and the lipid deposition in the liver tissue was observed under an optical microscope.

[0031] 2.8 Immunohistochemical staining for changes in liver tissue Paraffin sections were dewaxed, antigen-retrieved, and blocked. They were then incubated overnight at 14 °C with primary antibody PI3K, AKT, and FOXO. A secondary antibody mixture was added, and the sections were incubated at 37 °C for 30 min. After DAB staining at room temperature, the sections underwent hematoxylin staining, dehydration, clearing, and resin mounting. A panoramic scan was performed, and 400x magnification microscopic images were acquired. The area of ​​positive expression regions was calculated using ImageJ software.

[0032] 2.10 RT-qPCR detection of liver mRNA expression Liver tissue underwent RNA extraction, RNA concentration detection, reverse transcription to synthesize cDNA, and then RT-qPCR was performed, using GAPDH as an internal control, with 2− △△ct The relative expression level of the target gene was calculated using a method that was employed. All primers were synthesized by Beijing Qingke Biotechnology Co., Ltd. (Chengdu). Primer sequences are shown in Table 1.

[0033] Table 1 Primer Information

[0034] 2.11 Statistical Analysis SPSS 26.0 was used for statistical analysis of the experimental data. One-way ANOVA with LSD test was performed. Results are expressed as mean ± standard error (Mean ± SEM). P < 0.05 indicates that the difference is statistically significant.

[0035] 3 Results 3.1 Network pharmacological analysis of Compound Baiqi Pill for the treatment of glucose and lipid metabolism syndrome Using the TCMSP database, 75 active ingredients were identified from Compound Baiqi Pill, including stigmasterol, berberine, berberine, verbascoside, quercetin, chlorogenic acid, ascorbic acid, and anthocyanins. After removing duplicate targets, 663 compound-related targets were retained. 1204 disease targets were screened, and the intersection of these targets with the target group yielded 200 overlapping targets. The results are as follows: Figure 2 As shown in Figure A.

[0036] A "drug-component-target" network graph was constructed using Cytoscape 3.9.1 software, containing 742 nodes and 3435 edges. Figure 2 B). Among them, the active ingredients B23 (stigmasterol), C9 (β-sitosterol) and D14 (quercetin), as well as the core targets CYP19A1, ESR2 and ESR1 have many connections, indicating that the above ingredients and targets may play an important role in the treatment of glucose and lipid metabolism syndrome by Compound Baiqi Pill.

[0037] KEGG pathway enrichment analysis was performed on the intersection targets using the DAVID database, identifying 168 significant pathways. The top 20 pathways with the highest enrichment levels are presented here. Figure 2 C), mainly including the PI3K-AKT signaling pathway, the MAPK signaling pathway, and the AGE-RAGE signaling pathway. Given the central role of the PI3K-AKT signaling pathway in the development of glucose and lipid metabolism disorders...

[28] This study chose this pathway to explore the potential mechanism of action of Compound Baiqi Pill in treating glucose and lipid metabolism syndrome.

[0038] 3.2 Effect of Compound Baiqi Pill on the General Condition of Rats with Glucose and Lipid Metabolism Syndrome Compared with the model group, there was no difference in the body weight of rats in each group before drug administration. P >0.05), indicating that the grouping in this experiment conformed to the correct randomization method. Results Figure 3 As shown in A, 3D-F.

[0039] Depend on Figure 3 As shown in Figure A, after 13 weeks of high-fat diet feeding, intraperitoneal injection of STZ in rats resulted in a significant decrease in body weight in all groups. From week 17 onwards, the body weight of the model group was significantly lower than that of the control group. P < 0.01), after treatment with Compound Baiqi Pill and positive control drug, their body weight was higher than that of the model group ( P < 0.05).

[0040] Depend on Figure 3 DF analysis showed that, compared with the control group, the model group rats had significantly increased food intake, water intake, and urine output. P < 0.01), after treatment with Compound Baiqi Pills and positive control drugs, the patient's food intake, water intake, and urine output were all lower than those of the model group, with the high dose of Compound Baiqi Pills showing the most significant effect. P < 0.01), indicating that Compound Baiqi Pill has the effect of improving the "three highs and one low" symptoms in rats with glucose and lipid metabolism syndrome.

[0041] 3.3 The effect of Compound Baiqi Pill on improving hyperglycemia and impaired glucose tolerance in rats with glucose and lipid metabolism syndrome result Figure 3 B and Figure 3 As shown in C.

[0042] Depend on Figure 3 As shown in B, compared with the blank group, the fasting blood glucose level of rats in the model group was significantly increased ( P < 0.01), after treatment with Compound Baiqi Pills and positive control drugs, their blood glucose levels were significantly lower than those in the model group, with the high dose of Compound Baiqi Pills showing the most significant effect. P < 0.01), indicating that Compound Baiqi Pill has the effect of improving elevated blood glucose in rats with glucose and lipid metabolism syndrome.

[0043] Depend on Figure 3 As shown in C, after oral glucose administration, the blood glucose levels of rats in all groups reached their peak within 30 or 60 minutes, and then slowly decreased within 120 minutes. Compared with the control group, the blood glucose levels in the model group remained at a higher level throughout. P <0.01), while the blood glucose levels in the Compound Baiqi Pill and positive control drug groups were consistently lower than those in the model group. Among them, the blood glucose levels in the high-dose Compound Baiqi Pill group and the Xuezhikang group were consistently lower than those in the other groups, and showed a significant difference from the model group ( P < 0.01), indicating that Compound Baiqi Pill has the effect of improving glucose tolerance in rats with glucose and lipid metabolism syndrome.

[0044] 3.4 Compound Baiqi Pill Reduces Blood Lipid Levels in Rats with Glucose and Lipid Metabolism Syndrome result Figure 4 A and Figure 4 As shown in B.

[0045] Depend on Figure 4 A and Figure 4 As shown in B, compared with the blank group, the serum TC and TG levels in the model group rats were significantly increased ( P <0.01), after treatment with Compound Baiqi Pill and positive control drug, the TC and TG contents of the rats were significantly lower than those of the model group, indicating that Compound Baiqi Pill has the effect of improving lipid metabolism disorder in rats with glucose and lipid metabolism syndrome.

[0046] 3.5 Compound Baiqi Pill Improves Liver Pathological Changes in Rats with Glucose and Lipid Metabolism Syndrome result Figure 4 As shown in C-4E.

[0047] Depend on Figure 4 As shown by C, compared with the blank group, the liver index of rats in the model group was significantly increased ( P < 0.01), after treatment with Compound Baiqi Pill and positive control drugs, the liver index decreased significantly ( P < 0.01). Further examination of liver function revealed that the serum ALT and AST levels in the model group rats were significantly higher than those in the blank group ( P < 0.05, Figure 4 DE), while after administration of Compound Baiqi Pill and positive control drug, the ALT and AST levels were significantly reduced ( P < 0.05), indicating that Compound Baiqi Pill has a certain effect on improving liver function in rats with glucose and lipid metabolism syndrome.

[0048] 3.6 Compound Baiqi Pill Improves Hepatic Oxidative Stress Levels in Rats with Glucose and Lipid Metabolism Syndrome result Figure 5 As shown.

[0049] Depend on Figure 5 It can be seen that, compared with the blank group, the levels of SOD and GSH in the liver of rats in the model group were significantly reduced. P <0.05), the content of MDA increased significantly ( P < 0.01). After treatment with different doses of Compound Baiqi Pill and positive control drugs, the levels of SOD and GSH increased to varying degrees, with the most significant increase observed in the high-dose group. P < 0.05), while the MDA content decreased significantly ( P < 0.05), indicating that Compound Baiqi Pill has a certain ameliorative effect on the liver oxidative stress level in rats with glucose and lipid metabolism syndrome.

[0050] 3.7 Effects of Compound Baiqi Pill on Histopathological Changes of Pancreas and Liver in Rats with Glucose and Lipid Metabolism Syndrome result Figure 6 As shown in A-6C.

[0051] Depend on Figure 6 As shown in Figure A, HE staining results indicated that, compared with the blank group, the number of pancreatic islet cells in the model group rats was reduced, their arrangement was uneven, and they exhibited shrinkage. After treatment with Compound Baiqi Pill and positive control drugs, the pancreatic tissue structure was intact, clear, and neatly arranged.

[0052] Depend on Figure 6 B and Figure 6 As shown in C, compared with the blank group, the model group showed disordered hepatocyte arrangement, blurred nuclear boundaries, watery degeneration, and extensive and dense lipid distribution. After treatment with Compound Baiqi Pill and positive control drug, the hepatocyte structure was intact and clear, the arrangement was neat, the watery degeneration was improved, and the lipid deposition was reduced, indicating that Compound Baiqi Pill can improve the abnormal accumulation of fat and liver pathological damage in the liver of rats with glucose and lipid metabolism syndrome.

[0053] 3.8 Effects of Compound Baiqi Pill on the Expression of PI3K, AKT and FOXO1 Proteins in Rats with Glycolipid Metabolism Syndrome See results Figure 7 .

[0054] Depend on Figure 7 It was observed that PI3K and AKT proteins exhibited brownish-yellow or brown granular staining in the cytoplasm of hepatocytes. Compared with the control group, the positive expression of PI3K and AKT proteins in the model group was reduced. P < 0.01), while the different dose groups of Compound Baiqi Pill and the positive control group all increased the protein expression of PI3K and AKT in the liver to varying degrees. P < 0.01).

[0055] Unphosphorylated FOXO1 protein is predominantly brownish-yellow in the hepatocyte nucleus; after phosphorylation, its brownish-yellow color is mainly present in the cytoplasm. Compared with the control group, the model group showed positive expression of FOXO1 protein, with decreased expression in the cytoplasm and increased expression in the nucleus, but overall a decreasing trend. P < 0.01), while the different dose groups of Compound Baiqi Pill and the positive control group all increased the expression of FOXO1 protein in the cytoplasm of hepatocytes to varying degrees. P < 0.05).

[0056] 3.9 Compound Baiqi Pill Improves the mRNA Expression of PI3K, AKT and FOXO1 in the Liver of Rats with Glucose and Lipid Metabolism Syndrome The results are as follows Figure 8 As shown.

[0057] Depend on Figure 8 As shown in Figure A, compared with the control group, the expression of IL-6, IL-1β, and TNF-α in the liver of rats in the model group was significantly increased. P < 0.01), while the different dose groups of Compound Baiqi Pill and the positive control group all reduced the expression of IL-6, IL-1β and TNF-α in the liver to varying degrees. P < 0.05), indicating that the administration of Compound Baiqi Pill can reduce the level of inflammatory cell infiltration in the liver of rats with glucose and lipid metabolism syndrome.

[0058] Depend on Figure 8 As shown in B, compared with the control group, the mRNA expression of PI3K and AKT in the liver of rats in the model group was significantly reduced. P < 0.01), FOXO1 expression was significantly increased ( P < 0.01). Different doses of Compound Baiqi Pills and the positive control group all increased the expression of PI3K and AKT in the liver to varying degrees, while decreasing the expression of FOXO1 (…). P < 0.01).

[0059] In summary, the Compound Baiqi Pill of this invention can effectively reduce blood glucose levels in rats with glucose and lipid metabolism syndrome, enhance glucose tolerance, reduce serum TC, TG, ALT, and AST levels, increase SOD and GSH in the liver, reduce MDA content, decrease hepatic lipid accumulation, inflammatory cell infiltration, and hepatic fibrosis, and increase the mRNA and protein expression of PI3K, AKT, and forkhead box transcription factor 1 (FOXO1) in the liver. Therefore, the Compound Baiqi Pill can effectively improve the symptoms of glucose and lipid metabolism disorders in rats with glucose and lipid metabolism syndrome, and its mechanism of action may be related to the activation of the PI3K / AKT signaling pathway, thereby reducing hepatic oxidative stress and inflammatory damage.

[0060] This invention establishes a rat model of glucose and lipid metabolism syndrome using a high-sugar, high-fat diet combined with STZ. The model group rats exhibited typical symptoms of polydipsia, polyphagia, polyuria, and weight loss ("three highs and one low"), accompanied by elevated blood glucose, increased serum TC, TG, ALT, and AST levels, and aggravated pathological changes such as increased hepatic lipid deposition. After modeling, the fasting blood glucose concentration was ≥ 16.7 mmol / L. -1 As a direct standard for establishing a diabetes model, the combined effects of multiple indicators, including the aforementioned disorders of glucose and lipid metabolism and liver dysfunction, confirm the successful establishment of a glucose and lipid metabolism syndrome model. After intervention with Compound Baiqi Pill, the aforementioned abnormal indicators in the model rats were significantly improved, and the efficacy showed a certain dose-dependent effect. In alleviating the symptoms of polyuria, polydipsia, polyphagia, and weight loss, and lowering blood glucose, the high dose showed the most significant effect. Regarding the regulation of blood lipids and liver function, different doses exhibited different characteristics: the high dose had the strongest effect in lowering TG and AST, the medium dose had a better effect on improving ALT, while the low dose showed a certain advantage in regulating TC.

[0061] The results indicate that oxidative stress and inflammation are key pathological factors inducing glucose and lipid metabolism disorders. Decreased antioxidant markers (SOD, GSH) and increased pro-oxidative and pro-inflammatory factors (MDA, IL-6, IL-1β, TNF-α) in model animals collectively constitute the pathological basis for insulin resistance. These abnormalities may exacerbate metabolic disorders by interfering with key insulin signaling pathways. Among these pathways, the PI3K / AKT pathway, as a core pathway of insulin signaling, plays a crucial role in the regulation of lipid metabolism and glucose homeostasis; its functional inhibition is considered an important molecular bridge connecting oxidative stress, inflammation, and insulin resistance. Experimental data suggest that oxidative stress and inflammatory factors may affect the activity of its downstream key transcription factor FOXO1 by inhibiting the activation of the PI3K / AKT pathway. Under normal conditions, activated AKT phosphorylates and inactivates FOXO1, inhibiting hepatic gluconeogenesis. However, when the PI3K / AKT pathway is inhibited by oxidative stress or inflammatory factors, FOXO1 remains activated due to insufficient phosphorylation, thereby promoting the expression of key gluconeogenesis enzymes and ultimately exacerbating insulin resistance and glucose metabolism disorders. Therefore, regulating the PI3K / AKT / FOXO1 signaling pathway may be a key step in improving glucose and lipid metabolism disorders, providing a theoretical basis for elucidating the mechanism of action of drug interventions.

[0062] The foregoing description of specific exemplary embodiments of the invention is for illustrative and explanatory purposes. These descriptions are not intended to limit the invention to the precise forms disclosed, and it will be apparent that many changes and variations can be made in accordance with the foregoing teachings. The exemplary embodiments were chosen and described in order to explain the specific principles of the invention and its practical application, thereby enabling those skilled in the art to implement and utilize various different exemplary embodiments of the invention, as well as various different choices and variations. The scope of the invention is intended to be defined by the claims and their equivalents.

Claims

1. A compound Baiqi pill, characterized in that, The Compound Baiqi Pill is prepared from the following ingredients by weight: 10-25 parts of Phellodendron bark, 40-80 parts of Astragalus root, 20-40 parts of Rehmannia root, and 10-30 parts of hawthorn leaf.

2. The Compound Baiqi Pill according to claim 1, characterized in that, The Compound Baiqi Pill is prepared from the following ingredients by weight: 20 parts of Phellodendron bark, 60 parts of Astragalus root, 30 parts of Rehmannia root, and 20 parts of hawthorn leaf.

3. A method for preparing the Compound Baiqi Pill according to claim 1 or 2, characterized in that, Includes the following steps: S1. Take two-thirds of the medicinal materials in 310 times the prescription amount, add 12 times the weight of water and decoct 3 times, 1 hour each time. Combine the filtrates, filter, concentrate under reduced pressure, and spray dry to obtain dry extract powder. S2. Take the remaining amount of the prescribed medicinal materials, dry them, pulverize them, and pass them through a 100-mesh sieve to obtain fine powder; S3. Mix the dry powder obtained in S1 with the fine powder obtained in S2, add 60% ethanol, make into pills by molding method, and dry at 60℃ for 8 hours to obtain the compound Baiqi pills.

4. The use of the Compound Baiqi Pill as described in claim 1 or 2 in the preparation of a drug for treating glucose and lipid metabolism syndrome.

5. The use of the Compound Baiqi Pill as described in claim 1 or 2 in the preparation of drugs that lower triglycerides (TG) and aspartate aminotransferase (AST).

6. The use of the Compound Baiqi Pill as described in claim 1 or 2 in the preparation of drugs that improve alanine aminotransferase (ALT).

7. The use of the Compound Baiqi Pill as described in claim 1 or 2 in the preparation of a drug for regulating total cholesterol (TC).

Images