Exploration of the Mechanism and Active Targets of Chinese Herbal Formula, JTTZ, for the Treatment of Type 2 Diabetes with Obesity and Hyperlipidemia Based on Network Pharmacology

BackgroundPrevious studies have indicated that the JTTZ formula exhibits clinical benefit in T2D with obesity and hyperlipidemia such as lowering blood glucose, blood lipids, weight, and ameliorating symptoms as well as regulating islet function. However, their mechanism of action remains unclear. T2D with obesity and hyperlipidemia is associated with a severely poor management duo to difficulty in achieving the clinical goals and lack of effective multi-targeted therapies. In this study, we explored its potential mechanisms and therapeutic targets by network pharmacology. MethodsThe active ingredients and targets of JTTZ were obtained in the TCMSP, TCMID, TCM Database@Taiwan, PubChem and Swiss Target Prediction. And the therapeutic targets were searched from TTD, DrugBank Database and DisGeNET. Then, topology analysis were used as secondary screens to identify key hubs of the network. Finally, the data was integrated by Cytoscape software to construct a common network module. PPI networks were visualized to identify the interaction of the candidate targets. GO and KEGG pathway analysis were implemented. Rerult: 110 active compounds and 166 candidate targets of JTTZ against T2D with obesity and hyperlipidemia were obtained to construct compound-targets network. And, the therapeutic targets AKT2, RELA, NFKB1 and GSK3B were identified. GO and KEGG pathway analysis indicated that the biological processes related to inflammatory response, insulin secretion, steroid and bile acid metabolism, and 13 pathways mainly including adipocytokine signaling pathway, cAMP signaling pathway and cGMP-PKG signaling pathway were enriched. ConclusionOur data established that JTTZ intervenes with adipose tissue dysfunction via regulating to the adipocytokine (leptin and adiponectin), AMPK signaling pathway, cAMP and cGMP-PKG signaling pathway, inhibits systematic inflammatory response by NF-κB and MAPK signaling pathway, and ameliorates insulin resistance through PI3K/AKT2 pathway, all of which could thus offer a promising therapeutic strategy. In addition, AKT2, RELA, NFKB1 and GSK3B were identified to be regarded as potential therapeutic targets as well.