Exploration of Rule and Mechanism of Traditional Chinese Medicine in the Treatment of Diabetes with Ischemic Stroke Based on Chinese Herbal Network and Target Network

LI Qingli; LI Hao; XIE Yanming; LIU Yi

Abstract：Objective Based on the literature sources of medical cases,this study aimed to construct a network analysis of traditional Chinese medicine(TCM)for the treatment of diabetes mellitus(DM)with ischemic stroke(IS),and to explore the compatibility rules of TCM prescriptions.Furthermore,the study aimed to analyze the mechanism of action of the core TCM prescriptions based on target network analysis.Methods CNKI,VIP,Wanfang Database and China Biomedical Literature Service System,were used as the literature sources.Data statistics,association rule analysis,complex network analysis,and cluster analysis of Prescriptions in Literatures Based on Ancient and Modern Medical Case Cloud Platform,then get the core prescription.Analyze the composition rules of TCM.The TCM ingredients and corresponding targets were retrieved from the TCM Systems Pharmacology Database(TCMSP),while the targets related to DM and IS were obtained from the OMIM,TTD,and GeneCards databases.The core ingredients and key targets of the core TCM prescriptions were obtained using Cytoscape 3.9.1 software and the MCODE plugin.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted,followed by molecular docking validation.Results A total of 144 articles and 239 prescriptions were included,involving 194 TCM herbs.Astragalus membranaceus was the most frequently used herb(103 occurrences).Association rule analysis identified six combinations of herbs.The core TCM prescriptions consisted of nine herbs.The effective ingredients of the core TCM prescriptions included quercetin,hirudinoidine A,dihydrocapsaicin,arachidonicacid,etc.Key targets include mitogen-activated protein kinase 3(MAPK3),transcription factor JUN(JUN),tumor protein P53(TP53),signal transducer and activator of transcription 3(STAT3),SRC proto-oncogene(SRC),protein kinase B1(AKT1),mitogen-activated protein kinase 1(MAPK1),HRAS proto-oncogene(HRAS),coagulation factor Ⅱ(F2)and so on.GO and KEGG analysis showed that the treatment of DM with IS was related to cancer pathway,Advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway,phosphatidylinositol-3-kinase(PI3K)/AKT signaling pathway,cyclic adenosine monophosphate(cAMP)and other signaling pathways.Molecular docking showed that the active ingredients and key targets could form a stable structure.Conclusion By constructing chinese herbal network and target network,It was concluded that the treatment of DM with IS by TCM is mainly based on invigorating Qi and nourishing Yin,and activating blood circulation.It is also verified that the effective components of the core prescription play a role by acting on the body multi-target and multi-pathway,providing a reference for clinical treatment and further research.