Clinical Study And Target Exploration Of Jianpi Xiaoke Decoction For The Treatment Of T2DM

Objective:To observe the clinical efficacy and safety evaluation of Jianpi Xiaoke Decoction in the treatment of patients with spleen deficiency and heat stasis evidence of thirst disorders,and to explore its potential molecular mechanism of action in combination with network pharmacology,so as to provide clinical basis and theoretical support.Methods:1.clinical study: patients who met the inclusion criteria were collected and randomly divided into the herbal intervention group and the control group.The relevant information including TCM symptom score,clinical biochemical indexes including glucose metabolism(FPG,2h PG,Hb A1c),lipid metabolism(TG,TC,LDL-C,HDL-C),islet function indexes(FINS,FCP,HOMA-IR,HOMA-β),waist circumference,BMI,body weight and safety indexes were observed and recorded before and after treatment in both groups.After statistical analysis,the clinical efficacy and safety were systematically evaluated.2.Network pharmacology study: TCMSP,BATMAN-TCM,Gene Cards,NCBI,Dis Ge NET databases and Venny platform were used to obtain and screen the active ingredients and potential targets of Jianpi Xiaoke Decoction.Using Cytoscape3.8.0 and STRING platform,the core targets and key components were screened and analyzed,and GO function and KEGG pathway enrichment analyses were performed to identify key pathways and mechanisms of action,so as to construct a "Jianpi Xiaoke Decoction —herbal ingredients—potential targets—T2DM" interplay.The results of the analysis were summarized and visualized.Results:1.Clinical study: Statistical analysis showed that there was no statistically significant difference between the basic data,glucose metabolism,lipid metabolism,insulin,and obesity indexes of the patients in the western control group and the Chinese herbal medicine treatment group before treatment(P>0.05),indicating that the data of the two groups before treatment were comparable.After the follow-up intervention according to the treatment protocol,the obesity index,glucose and lipid metabolism,and insulin function in the Chinese medicine group and the control group showed significant improvement compared with the treatment(P<0.05);the differences in the Chinese medicine evidence score,integral efficacy,glucose and lipid metabolism,insulin secretion and resistance index,and obesity index between the Chinese medicine intervention group and the control group after treatment were statistically significant(P<0.05).After combining the statistical results,it was found that the combination of Jianpi Xiaoke Decoction and Metformin Hydrochloride Tablets could effectively alleviate many clinical symptoms of T2 DM patients,regulate the level of glucose and lipid metabolism,and have significant efficacy in reducing fat and weight,improving the secretory function of pancreatic islet cells and insulin resistance.2.Network pharmacology study: 171 compound components and 3121 targets of 6 Chinese herbal medicines of Jianpi Xiaoke Decoction were obtained after searching,selecting and de-weighting,4576 targets of obesity,2531 targets related to T2 DM and 380 common targets of drugs and diseases.104 key targets were screened according to Degree value,and the top-ranked core targets were AKT1,SRC,TP53,JUN,MAPK1,RELA,PIK3R1,etc.10 gene clusters and 8 core genes were obtained,and the main core genes were E2F1,CXCL2,IGF1,GOT1,etc.;the key components were p-coumaric acid,cypionol,The key components were p-coumaric acid,cypriol,geraniol,rape oil sterol,glutathione,quercetin,etc.A total of 3637 gene biological processes,243 molecular functions,135 cellular components and 200 signaling pathways were screened.GO and KEGG pathway enrichment and diagrams showed that Jianpi Xiaoke Decoction Chinese medicine acts mainly in cell membrane rafts,membrane microdomains,membrane regions,vesicle lumen and other locations,involving responses to nutrient levels,drugs,lipopolysaccharides,peptide hormones,lipid metabolic processes,the related stress,reactive oxygen species response and other biological processes;signaling receptor ligand activity and binding,transcription factor binding,cytokine binding,steroid binding,heme binding and other molecular functions;while the efficacy of the Jianpi Xiaoke Decoction may be achieved with the help of signaling pathways such as AGE-RAGE,TNF,IL-17,HIF-1,Toll-like receptors,endocrine resistance,insulin resistance,apoptosis,lipid and atherosclerosis,and other mechanisms of action associated with diabetic cardiomyopathy,non-alcoholic fatty liver disease,and cancer-related biological processes.Conclusion:1.The combination of Jianpi Xiaoke Decoction with Metformin Hydrochloride Tablets can effectively improve clinical symptoms,laboratory indices of glucose and lipid metabolism and reduce body weight and abdominal fat accumulation in obese patients with achalasia and has better efficacy than Metformin Hydrochloride Tablets alone in all aspects of treatment,and no adverse effects occurred during the study with high safety.2.It is possible that Jianpi Xiaoke Decoction works through multiple components,represented by AKT1,TP53,JUN as multiple targets,involving AGE-RAGE,HIF-1,Toll-like receptors and other pathways,through the direct or indirect action of a variety of tissues,cells and proteins,regulating insulin resistance,apoptosis,lipid metabolism and other common effects,with inflammatory response,oxidative stress,glucolipid metabolism.It is closely related to the inflammatory response,oxidative stress,and glucolipid metabolism,thus providing new ideas and directions for the follow-up study.