| Objective:Based on network pharmacology,the active ingredients and core targets of traditional Chinese medicine Yitangkang in the treatment of T2 DM were studied,and its biological process and pathway mechanism were predicted,and the predicted key signaling pathway IL-17 signaling pathway was verified by animal experiments.Clinical treatment of T2 DM provides new ideas and evidence.Methods:1.Based on the TCMSP database to screen all the active ingredients and targets of the traditional Chinese medicine compound Yitangkang,and intersect the T2DM-related genes retrieved in the Gene Cards,OMIM,TTD and Drug Bank databases,and establish the"Yitangkang" through Cytoscape 3.9.1 Drug-active ingredient-target" network,STRING database to build PPI network,Cyto NCA plug-in to screen core targets,R×64 4.1.2 to run the Cluster Profiler program for GO functional annotation and KEGG pathway enrichment analysis.2.70 SPF grade male Wistar rats were randomly divided into blank group(10 rats),model group(60 rats,model group,metformin hydrochloride group and traditional Chinese medicine compound Yitangkang)by random number table after adaptive feeding.T2 DM rat model was established by intraperitoneal injection of high-fat,high-sugar and streptozotocin(STZ)solution.After the modeling was completed,the rats were given intragastric administration in groups,once a day,and the materials were collected after continuous intragastric administration for 8 weeks..Detection of fasting blood glucose,fasting insulin,TG,TC,HDL-C,LDL-C and IL-17 signaling pathway in rats IL-17,IL-17 R,HSP90,TRAF6,MAPKs,AP-1,IL-6,COX2 protein expression level.Results:1.Network pharmacology results:(1)There are a total of 176 active ingredients in the traditional Chinese medicine compound Yitangkang,and a total of 238 targets;(2)There are 11,026 T2 DM disease-related targets,and 216 targets intersecting with the traditional Chinese medicine compound Yitangkang;(3)Quercetin,β-sitosterol,stigmasterol,baicalein,and formononetin are the key active ingredients of the drug,and PTGS2,NCOA2,PTGS1,ADRB2,and SCN5 A are key gene targets;(4)CDKN1A,FOS,MAPK14,IL2,AKT1 are the core targets of the traditional Chinese medicine compound Yitangkang in the treatment of T2DM;(5)2747 biological process entries were obtained from GO functional annotation,of which the response to lipopolysaccharide,the response to steroid hormones,the response to oxidative stress and reactive oxygen species,wound healing,and the response to ketones were the main biological processes;KEGG rich A total of 174 pathways were collected,of which lipid and atherosclerosis,AGE-RAGE,IL-17,TNF-α,endocrine resistance,Th17 cell differentiation and HIF-1 signaling pathways were the main pathways.2.Results of animal experiments:(1)Fasting blood glucose and fasting insulin levels: Compared with the blank group,the fasting blood glucose of the model group was significantly increased,and the fasting insulin level was significantly decreased(P<0.05);Fasting insulin levels were significantly improved,and the high-dose effect was more significant(P<0.05);compared with the metformin hydrochloride group,the high-dose Yitangkang group improved insulin levels more significantly(P<0.05),and there was no difference between the middle-dose group and the group.There was a significant difference(P>0.05),and the improvement ability of the low-dose group was weak(P<0.05).(2)Blood lipid levels: Compared with the blank group,the blood lipid levels of the model group were significantly worse(P<0.05);The lipid-lowering effect of the dose group was better(P<0.05);compared with the metformin hydrochloride group,the high-dose Yitangkang group could significantly increase HDL-C(P<0.05),and there was no significant difference between the middle-dose group and the group(P<0.05).P>0.05),the low-dose group had no significant difference in reducing the level of LDL-C(P>0.05),but the improvement in other levels was weak(P<0.05).(3)Expression levels of IL-17 signaling pathway proteins in adipose tissue: Compared withthe blank group,the expression levels of each protein in the model group were significantly increased(P<0.05);compared with the model group,the expression levels of each protein in the Yitangkang high school and low dose groups were significantly increased Compared with metformin hydrochloride group,Yitangkang high-dose group down-regulated the expression levels of various proteins more significantly(P<0.05),and there was no significant difference between the middle-dose group and the group(P>0.05),the low-dose group had weaker down-regulation ability(P<0.05).Conclusions:1.The traditional Chinese medicine Yitangkang can act on CDKN1 A,FOS,MAPK14,IL2,AKT1 and other core targets through quercetin,β-sitosterol,stigmasterol,baicalein,formononetin and other active ingredients.,through AGE-RAGE,IL-17,TNF-α and HIF-1signaling pathways,play the role of regulating glucose and lipid metabolism,anti-inflammatory,anti-oxidative stress and so on.2.The traditional Chinese medicine compound Yitangkang can inhibit the IL-17 signaling pathway,inhibit the inflammatory response,and achieve anti-inflammatory effects by down-regulating the protein expression levels of IL-17,IL-17 R,HSP90,TRAF6,MAPKs,AP-1,IL-6,and COX2.inflammation,improve glucose and lipid metabolism and insulin secretion.3.The efficacy of traditional Chinese medicine compound Yitangkang in the treatment of T2 DM is related to the dose,and sufficient doses of drugs can play a better therapeutic effect.4.It is scientific,feasible and credible to predict the mechanism of traditional Chinese medicine compound treatment of diseases through network pharmacology,and provide methods and ideas for the modern research of traditional Chinese medicine. |
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