Preparation and application of xojia-4 soup

Abstract

The application belongs to the technical field of medicine, and provides preparation and application of Xiega-4 decoction, including the following steps: turmeric, tribulus terrestris, gardenia, and phellodendron are respectively crushed into powder through an 80-mesh sieve, and Xiega-4 decoction compound preparation is prepared according to a ratio of 5:5:4:3; the application also provides experimental research application of Xiega-4 decoction in network pharmacology and experimental research application in a hyperglycemic rat model; the application predicts and verifies the blood glucose lowering mechanism of Xiega-4 decoction in the treatment of type II diabetes by network pharmacology and animal experiment method, finds that the blood glucose lowering effect of Xiega-4 decoction is related to the increase of AR, HSP90AA1, STAT1, C peptide and INS levels, and provides experimental data reference for the action mechanism of Xiega-4 decoction in the treatment of diabetes.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically the preparation and application of Xieriga-4 decoction. Background Technology

[0002] With the continuous improvement of people's living standards and the increasing aging of the population, the incidence of diabetes is showing an upward trend year by year, and it has become the most important chronic metabolic disease in the world. Therefore, the continuous development of hypoglycemic drugs has become the focus of researchers. At present, the treatment of diabetes mainly relies on Western medicine. Although Western medicine has significant efficacy, it also has many obvious adverse reactions. The application of natural medicines has a long history in my country, especially in the prevention and treatment of chronic diseases such as diabetes, with unique advantages, including mild, long-lasting efficacy and high safety.

[0003] Type 2 diabetes mellitus (T2DM) is an endocrine and metabolic disease based on insulin resistance and insufficient insulin secretion, characterized by polydipsia, polyphagia, polyuria, and weight loss. Its prevalence is increasing worldwide, and the number of T2DM patients is projected to exceed 439 million by 2030. Complications caused by diabetes often affect multiple organs, severely impacting patients' physical and mental health and quality of life, becoming a significant burden on families and society. T2DM is associated with gut microbiota dysbiosis. Studies have found that compared to healthy individuals, T2DM patients have a significantly reduced number of Firmicutes and an increased number of Bacteroidetes. The Bacteroidetes-to-Firmite ratio is positively correlated with decreased glucose tolerance. Compared to normal feces, T2DM patients show an increase in four types of lactic acid bacteria and a decrease in five types of Clostridium. Glycated hemoglobin and blood glucose levels are positively correlated with lactic acid bacteria abundance and negatively correlated with Clostridium abundance.

[0004] The gut microbiota, often referred to as the "invisible organ" carrying the body's "second gene," has gradually become a research hotspot and is even considered an endocrine organ. Alterations in the structure and function of the gut microbiota can promote obesity. In obese individuals, the accumulation of abdominal fat leads to decreased glucose utilization by tissues such as the liver and muscles. Furthermore, elevated levels of non-esterified fatty acids and inflammatory factors in obese individuals can generate endoplasmic reticulum stress and oxidative stress, resulting in insulin resistance. The risk of developing diabetes is closely related to the degree of obesity. Therefore, regulating the gut microbiota and lowering blood lipids has become one of the effective ways to prevent and treat type 2 diabetes mellitus (T2DM).

[0005] Although there have been reports on the mechanism of action of Xieriga-4 decoction in treating diabetic nephropathy, the complex etiology, complications, and composition of Xieriga-4 decoction make it difficult to fully and deeply reveal its mechanism of action in treating diabetes.

[0006] To this end, those skilled in the art have proposed a method for preparing Xieriga-4 decoction and its application in a hyperglycemic rat model. Through a combination of network pharmacology and animal experiments, the aim is to explore the hypoglycemic mechanism of Xieriga-4 decoction, elucidate its mechanism of action, and provide a certain theoretical basis for further development and research in the future. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention provides the preparation and application of Xieriga-4 decoction, thereby resolving the issues mentioned in the background art.

[0008] According to the first aspect of this disclosure, a method for preparing Xieriga-4 Decoction is provided, comprising the following steps: pulverizing turmeric, tribulus terrestris, gardenia, and phellodendron bark into powder and passing them through an 80-mesh sieve, and preparing a compound preparation of Xieriga-4 Decoction in a ratio of 5:5:4:3; and weighing 5.04 g / kg of each according to the prescribed dosage. -1 2.52 g·kg -1 1.26 g·kg -1 Add 20ml of boiling water to prepare different doses of Xieriga-4 decoction.

[0009] According to the second aspect of this disclosure, the application of Xieriga-4 decoction in network pharmacology is proposed.

[0010] According to the third aspect of this disclosure, the application of Xieriga-4 decoction in a hyperglycemic rat model is proposed.

[0011] Specifically, the effects included on the body weight of hyperglycemic model rats, the blood glucose levels of hyperglycemic model rats, the four lipid indicators of hyperglycemic model rats, the serum levels of hyperglycemic model rats, and the gut microbiota of hyperglycemic model rats.

[0012] Compared with the prior art, the present invention has the following beneficial effects:

[0013] 1. This invention uses network pharmacology and animal experiments to predict and verify the hypoglycemic mechanism of Xieriga-4 decoction in treating type II diabetes. It was found that the hypoglycemic effect of Xieriga-4 decoction is related to the increase of AR, HSP90AA1, STAT1, C peptide and INS levels, providing experimental data reference for the mechanism of Xieriga-4 decoction in treating diabetes.

[0014] 2. The Xie Ri Ga-4 decoction of this invention is composed of turmeric, phellodendron bark, gardenia, and tribulus terrestris. It can significantly reduce blood glucose in hyperglycemic model rats and significantly alleviate weight loss in diabetic model rats, thus having a good blood sugar control effect. Attached Figure Description

[0015] Figure 1 This is a network diagram of the "drug-ingredient" structure of the present invention, namely, Xieriga-4.

[0016] Figure 2 This is a target point diagram showing the intersection of the component targets and disease targets of the present invention;

[0017] Figure 3 This is a network diagram of the interaction targets between cyclophosphamide-4 and hyperglycemia in this invention;

[0018] Figure 4 This is a network diagram of the Xie Ri Ga-4-active ingredient-core target-hyperglycemia of the present invention;

[0019] Figure 5 The first 20 results of the GO of this invention are visualized; where BP represents the bioinformatics processing process; CC represents cell analysis; and MF represents molecular function.

[0020] Figure 6 This is a visualization of the first 20 results from the KEGG algorithm of this invention.

[0021] Figure 7 This is a Beta diversity NMDS analysis diagram from the present invention. Detailed Implementation

[0022] The embodiments of the present invention will be described in further detail below with reference to the accompanying drawings and examples. The following examples are for illustrative purposes only and should not be construed as limiting the scope of the invention.

[0023] Example 1: This invention provides a method for preparing Xieriga-4 Decoction, comprising the following steps: pulverizing turmeric, tribulus terrestris, gardenia, and phellodendron bark into powders and passing them through an 80-mesh sieve, and preparing Xieriga-4 Decoction compound preparation in a ratio of 5:5:4:3; and weighing 5.04 g / kg of each according to the dosage. -1 2.52 g·kg -1 1.26 g·kg -1 Add 20ml of boiling water to prepare different doses of Xieriga-4 decoction.

[0024] Example 2: The application of Xieriga-4 decoction in network pharmacology is also proposed.

[0025] The chemical components of the four ingredients in Xieriga-4 Decoction were screened and integrated using the TCMSP database, a systemic pharmacology database for traditional Chinese medicine. The target sites of the chemical components were predicted using the Uniport and DrugaBank databases. Using the keyword "hyperglycemia," searches were conducted in four databases: GeneCards, Drugbank, TTD, and PharmGKB, to collect and integrate relevant targets for hyperglycemia.

[0026] Using Venny 2.1.0 software, the intersection of the target points of Xieriga-4 decoction components and the target points of hyperglycemia was analyzed to screen out the target points that interact between Xieriga-4 decoction and hyperglycemia. Using the Sling database software, the interaction target points were input to obtain data on human target protein interactions, and a protein-protein interaction (PPI) network was constructed. The obtained data was analyzed using Cytoscape 3.6.1 software to obtain core targets and construct a "Xieriga-4 medicinal material-active component-core target-hyperglycemia pathway" network. Using Cytoscape 3.6.1 database software, GO enrichment and KEGG target pathway enrichment were performed on the obtained intersection target points to analyze the main related pathways and biological processes of hyperglycemia associated with Xieriga-4 decoction.

[0027] Result: As Figure 1 As shown, 61 chemical components of Xieriga-4 were collected and integrated using TCMSP, and 196 targets were predicted from the database. A drug-component network diagram was drawn using Cytoscape 3.6.1 software. Using R packages, four disease databases were integrated, and duplicate targets were removed, resulting in 3120 disease targets related to hyperglycemia.

[0028] like Figure 2 As shown, by intersecting the components with the disease targets, a total of 138 intersection targets were obtained, which are the target points for the treatment of hyperglycemia by Xie Riga-4.

[0029] like Figure 3 As shown, by inputting the intersection target points into the Sling database, a network diagram of the interaction targets between cyclophosphamide-4 and hyperglycemia is obtained.

[0030] like Figure 4 As shown, analysis using Cytoscape 3.6.1 software yielded 119 core targets, and a "Xieriga-4-active ingredient-core target-hyperglycemia" network was constructed.

[0031] like Figure 5 As shown, GO enrichment analysis of the intersection targets using the R package yielded 168 protein molecular functions, 55 cell groups, and 2278 biological responses. Each GO enriched item was sorted according to the number of targets it contained, and the top 20 GO enriched results were visualized.

[0032] As shown in Table 1 and Figure 6 As shown, KEGG target pathway annotation analysis was performed on the intersection targets using the R package, resulting in 177 KEGG signal pathways. Each KEGG enriched entry was sorted according to the number of targets it contained.

[0033] Table 1 Ranking of major pathways

[0034]

[0035] Network pharmacology identified 61 major active ingredients of Xieriga-4 and 3120 targets for hyperglycemia, of which 138 intersected with hypoglycemic effects. KEEG pathway enrichment analysis showed that the hypoglycemic effect of Xieriga-4 decoction is mainly related to lipid and atherosclerosis pathways, AGE-RAGE pathway, and IL-17 signaling pathway. PPI interaction network results showed that the main hypoglycemic targets of Xieriga-4 decoction are 31 key targets such as HSP90AA1 and STAT1.

[0036] Example 3: The application of Xie Ri Ga-4 Decoction in a hyperglycemic rat model was also proposed.

[0037] Animal grouping and model establishment: Seventy-two male SD rats were randomly divided into 6 groups: high-, medium-, and low-dose groups of Xieriga-4 decoction (5.04 g·kg⁻¹). -1 2.52 g·kg -1 1.26 g·kg -1 Rats were divided into a model group, a positive control group, and a blank control group, with 12 rats in each group. After being fed a high-sugar diet for 4 weeks, fasting blood glucose (FBG) levels were measured and recorded in each group. After blood glucose measurement, except for the normal control group, rats in other groups were intraperitoneally injected with 0.1 mmol / L of [a specific antibiotic]. -1 Streptozotocin (STZ) 35 mg / kg was prepared using citrate buffer solution (pH 4.5). -1 A hyperglycemia model was established. Fasting blood glucose (FBG) levels were measured in each group of rats on day 3 after modeling. For rats with FBG < 11.1 mmol / L... -1 Rats were given a second injection of STZ, and fasting blood glucose (FBG) was measured on day 3 after the second injection. If FBG was ≥11.1 mmol / L for two consecutive times, the result was considered satisfactory. -1 Simultaneous presence of the three polys and one less (polydipsia, polyphagia, polyuria, and weight loss) symptoms indicates successful model establishment. After successful model establishment, the blank group and the model group are given physiological saline, the positive group is given metformin, and the other groups are given Xieriga-4 decoction, which are administered by gavage for 30 consecutive days, once a day.

[0038] Fasting blood glucose levels were measured in each group of rats every 5 days during the gavage treatment period. Statistical significance was calculated. When the blood glucose level of the treatment group was statistically significant compared with the model group, blood was collected from the abdominal aorta under anesthesia. The blood samples were incubated in a 37°C water bath for 30 minutes, followed by a 3000 rpm induction respiration. -1Centrifuge for 15 min, collect serum, and collect rat feces under aseptic conditions and place in a -80℃ refrigerator. At the same time, weigh and record the five internal organs (heart, liver, spleen, lung, and kidney) and store them in 10% formaldehyde solution for later use. The 10% formaldehyde solution is prepared by mixing formaldehyde solution and ultrapure water in a ratio of 1:3, and the anesthetic is prepared by mixing chloral hydrate and physiological saline in a ratio of 1:9.

[0039] (1) Measure the blood glucose and weight of each group of rats: Measure the fasting blood glucose of each group of rats before and after modeling. After successful modeling, measure the fasting blood glucose of the rats once every 5 days. Weigh and record the weight of each rat once a week.

[0040] Changes in body weight of hyperglycemic model rats treated with Xieriga-4 decoction: As shown in Table 2, compared with the normal group, the body weight of the model group decreased significantly starting from week 6 (P<0.05). Compared with the model group, the body weight of the positive control group increased significantly starting from week 7, the medium-dose group of Xieriga-4 decoction increased significantly starting from week 6, and the low-dose group increased significantly starting from week 7 (P<0.01 or P<0.05).

[0041] Table 2. Changes in rat body weight (g)

[0042]

[0043] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0044] The effects of Xieriga-4 decoction on blood glucose levels in hyperglycemic model rats: As shown in Table 3, compared with the normal group, the blood glucose index of the model group increased significantly from day 20 (P<0.01 or P<0.05). Compared with the model group, the blood glucose levels of the positive group and the medium-dose group decreased significantly from day 35 (P<0.01 or P<0.05); the blood glucose levels of the high-dose group and the low-dose group decreased significantly from day 50 (P<0.05).

[0045] Table 3. Changes in blood glucose levels in rats (mmol / L) -1 )

[0046]

[0047] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0048] (2) Determination of rat serum indicators by fully automated biochemical analyzer: The collected serum was used to determine the levels of biochemical indicators HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), TG (triglycerides), and TC (total cholesterol) using a fully automated biochemical analyzer.

[0049] Effects of Xieriga-4 Decoction on four lipid indicators in hyperglycemic model rats: As shown in Table 4, compared with the normal group, the TG level in the model group was significantly decreased (p<0.01); TC, HDL, and LDL levels were significantly increased (p<0.01). Compared with the model group, the TG level in the positive group was increased (p<0.05); the TC level in the positive group and the high-dose group was decreased (p<0.05); and the TG and HDL levels in the high, medium, and low-dose groups were significantly decreased (p<0.05 or p<0.01).

[0050] Table 4. Effects of Xieriga-4 Decoction on TC, TG, HDL, and LDL in hyperglycemic rats.

[0051]

[0052] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, ** < 0.01.

[0053] (3) ELISA detection of C-peptide, INS, AR, STAT1 and HSP90AA1 levels in rat serum: Dissolve the prepared serum and detect the levels of C-peptide, INS, AR, STAT1 and HSP90AA1 respectively according to the ELISA kit instructions.

[0054] Effects of Xieriga-4 Decoction on serum AR, HSP90AA1, RXRA, C-peptide, and INS in hyperglycemic model rats: As shown in Table 5, compared with the normal group, the levels of AR, HSP90AA1, STAT1, INS, and C-peptide in the model group were significantly decreased (P<0.05 or P<0.01). Compared with the model group, the levels of AR, HSP90AA1, STAT1, and C-peptide in the positive control group and each dose group of Xieriga-4 Decoction were significantly increased (P<0.05 or P<0.01); the level of INS in the positive control group was significantly decreased (P<0.05); and the level of INS in the high-dose group of Xieriga-4 Decoction was significantly increased (P<0.05).

[0055] Table 5. Effects of serum AR, HSP90AA1, STAT1, INS, and C-peptide levels in rats of each group (mU·L) -1 )

[0056]

[0057]

[0058] Note: Compared with the normal group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01.

[0059] (4) Detection of 16S rDNA in rat feces: Total genomic DNA was extracted from aseptically extracted rat feces using CTAB. The purity and concentration of DNA were then detected by 1% agarose gel electrophoresis. An appropriate amount of sample was placed in an EP tube and diluted with sterile water to 1 ng / μl. -1 .

[0060] CTAB method operation steps:

[0061] S1. Fecal sample: Pipette 1000μm CTAB lysis buffer into a 2.0ml EP tube, add lysozyme, add an appropriate amount of sample to the lysis buffer, incubate in a 65℃ water bath, inverting and mixing several times during the process to ensure complete lysis of the sample.

[0062] S2. Centrifuge and collect the supernatant. Add phenol (pH 8.0): chloroform: isoamyl alcohol (25:24:1), invert and mix well. Centrifuge at 12000 rpm for 10 min.

[0063] S3. Take the supernatant, add chloroform:isoamyl alcohol (24:1) and mix by inversion, then centrifuge at 12000 rpm for 10 min.

[0064] S4. Pipette the supernatant into a 1.5ml EP tube, add isopropanol, shake up and down, and precipitate at -20℃.

[0065] Centrifuge at 12000 rpm for 10 minutes (S5), then pour out the liquid, being careful not to discard the precipitate. Wash twice with 1 ml of 75% ethanol. The remaining small amount of liquid can be collected by centrifugation again and then aspirated with a pipette tip.

[0066] S6. Dry in a clean bench or air dry at room temperature (avoid over-drying DNA samples, otherwise they will be difficult to dissolve).

[0067] S7. Add ddH2O to dissolve the DNA sample. If necessary, incubate at 55-60℃ for 10 minutes to aid dissolution.

[0068] S8. Add 1 μL of RNase A to digest RNA and incubate at 37°C for 15 min.

[0069] PCR amplification: The target region is the 16SV3+V4 region, and the upstream and downstream primer sequences are 341F (5'-CCTAYGGGRBGCASCAG-3') and 806R (5'-GGACTACNNGGGTATCTAAT-3').

[0070] PCR reaction system:

[0071] 2×Phus ion Master Mix............15μL

[0072] Forward Primer(0.2μM)............1μL

[0073] Reverse Primer(0.2μM)............1μL

[0074] gDNA (1 ng·μl) -1 )......................10ng

[0075] Add ddH2O to 2 μL

[0076] PCR reaction procedure: Step 1: 98℃ pre-denaturation for 1 min; Step 2: 98℃ denaturation for 10 s; 50℃ annealing for 30 s; 72℃ extension for 30 s, 30 cycles; Step 3: 72℃ extension for 5 min.

[0077] PCR product identification, purification, and quantification: PCR products were identified using 2% agarose gel electrophoresis; PCR products were purified using a Qiagen gel extraction kit, following the manufacturer's instructions; the PCR products were then... Quantification was performed using the DNA PCR-Free Sample Preparation Kit. The samples were mixed in appropriate proportions according to the sequencing volume requirements for each sample.

[0078] Effects of Xieriga-4 Decoction on Intestinal Microbiota in Hyperglycemic Model Rats: Figure 6 As shown, the Venn diagram (VENN) analysis results show that there are a total of 292 OTUs in the normal group, mode 1 group, and treatment group; there are 413 OTUs specific to the normal group, 894 in the mode 1 group, and 674 in the treatment group; there are 92 OTUs in the normal group and mode 1 group, and 47 OTUs in the treatment group.

[0079] Alpha and Beta diversity analysis: such as Figure 7 As shown in Table 6, to observe the differences in gut microbiota diversity among groups, the Chao1 index, Faith's Phylogegenic Diversity index, Observed OTU, Shannon index, and Simpson index were used to assess alpha diversity. Compared with the normal group, the model group showed significantly increased Chao1, faith_pd, Observed OTU, Shannon, and Simpson indices (p<0.01); compared with the model group, the treatment group showed significantly decreased faith_pd (p<0.01). There was a clear separation between the normol group and the model group, with significant differences. There was also a significant separation between the normol group and the treatment group, with some differences. A small separation existed between the treatment group and the model group, with differences remaining. Furthermore, Stress = 0.0812 < 0.2, therefore this analysis is relatively reliable.

[0080] Table 6 Comparison of α-diversity index of gut microbiota in rats of different groups

[0081]

[0082] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0083] Analysis of differences in gut microbiota results:

[0084] Phylum-level difference analysis: As shown in Table 7, compared with the normal group, the relative abundance of Firmicutes in the model group was significantly reduced (P<0.01); the relative abundance of Actinobacteria was increased (P<0.05).

[0085] Table 7 Comparison of relative abundance (%) of gut microbiota phyla in rats of different groups

[0086]

[0087] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0088] Analysis of differences at the family level: As shown in Table 8, compared with the normal group, the relative abundance of Lactobacillus family in the model group was significantly reduced (P<0.01); the relative abundance of Bifidobacterium family, Peptostreptococcus family and Clostridium family was increased (P<0.05 or P<0.01), and compared with the model group, the relative abundance of Peptostreptococcus family was increased (P<0.05).

[0089] Table 8. Comparison of relative abundance of family levels in the gut microbiota of rats in each group (%)

[0090]

[0091] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0092] Genus-level difference analysis: As shown in Table 9, compared with the normal group, the relative abundance of Lactobacillus in the model group was significantly reduced (P<0.01); the relative abundance of Bifidobacterium, Rombutzium, unclassified bacteria, and Clostridium _UCG_014 was increased (P<0.05). Compared with the model group, the relative abundance of Rombutzium was increased (P<0.05).

[0093] Table 9 Comparison of relative abundance of gut microbiota genera in different groups of rats (%)

[0094]

[0095] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0096] Analysis of differences at the order level: As shown in Table 10, compared with the normal group, the relative abundance of Lactobacilliles in the model group was significantly reduced (P<0.01); the relative abundance of Erysipelothrix, Bifidobacteria, and Bacteroidetes was significantly increased (P<0.01), and compared with the model group, the relative abundance of Trichophytonles was increased (P<0.05).

[0097] Table 10 Comparison of relative abundance (%) of gut microbiota orders in different groups of rats

[0098]

[0099]

[0100] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0101] Class-level difference analysis: As shown in Table 11, compared with the normal group, the relative abundance of Bacillus in the model group was significantly reduced (P<0.01); the relative abundance of Clostridium and Rhodobulobacterium was significantly increased (P<0.01).

[0102] Table 11 Comparison of relative abundance (%) of gut microbiota in different groups of rats

[0103]

[0104] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0105] Species-level difference analysis: As shown in Table 12, compared with the normal group, the relative abundance of unclassified bacteria and Bifidobacterium pseudolongum in the model group was significantly increased (P<0.01); the relative abundance of Lactobacillus johnsonii, Lactobacillus enterica, and Rosette was decreased (P<0.01 or P<0.05). Compared with the model group, the relative abundance of Lactobacillus enterica and Rosette was decreased (P<0.05).

[0106] Table 12 Comparison of relative abundance of gut microbiota species in different groups of rats (%)

[0107]

[0108] Note: Compared with the normal group, # p < 0.05, ## p < 0.01; compared with the model group, *p < 0.05, **p < 0.01.

[0109] The above studies show that Xieriga-4 decoction can significantly reduce blood glucose levels and increase body weight in type 2 diabetes mellitus (T2DM) model rats, effectively alleviating the "three highs and one low" symptoms. Regarding blood lipids, Xieriga-4 decoction significantly reduces serum TC, TG, and HDL levels, effectively inhibiting hyperlipidemia. In terms of gut microbiota diversity, Xieriga-4 decoction increases the relative abundance of Peptostreptococci, Rombutzella, and Trichophyton, while decreasing the relative abundance of Enterobacteriaceae and Roseola. In summary, through network pharmacology and animal experiments, the possible mechanism of Xieriga-4 decoction's hypoglycemic effect in treating type 2 diabetes mellitus was predicted and verified. The hypoglycemic effect of Xieriga-4 decoction may be related to increased levels of AR, HSP90AA1, STAT1, C-peptide, and INS. This provides some experimental data reference for understanding the mechanism of action of Xieriga-4 decoction in treating diabetes.

[0110] Furthermore, in order to provide a concise description of exemplary embodiments, not all features of actual embodiments (i.e., those features that are not relevant to the best mode of carrying out the invention as currently considered, or those features that are not relevant to implementing the invention) may be omitted.

[0111] It should be understood that numerous specific implementation decisions can be made during the development of any actual implementation method, and in any engineering or design project. Such development efforts may be complex and time-consuming, but for those of ordinary skill in the art who benefit from this disclosure, the development effort will be a routine work of design, manufacturing, and production without requiring much experimentation.

[0112] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. Application of Xieriga-4 Decoction in the preparation of drugs for regulating the intestinal flora of hyperglycemic organisms.

2. The application according to claim 1, characterized in that, The regulation of the gut microbiota includes: increasing the relative abundance of Firmicutes and decreasing the relative abundance of Actinobacteria.

3. The application according to claim 1, characterized in that, The regulation of the gut microbiota includes increasing the relative abundance of Lactobacillus and Peptostreptococci.

4. The application according to claim 1, characterized in that, The regulation of the gut microbiota includes increasing the relative abundance of Lactobacillus and Rombutzella.

5. The application according to claim 1, characterized in that, The preparation steps of Xieriga-4 Decoction are as follows: Turmeric, Tribulus terrestris, Gardenia jasminoides and Phellodendron chinense are pulverized into powder and passed through an 80-mesh sieve. They are then mixed in a weight ratio of 5:5:4:3 to obtain compound powder. The compound powder is weighed according to the dosage and 20ml of boiling water is added to prepare Xieriga-4 Decoction.

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