Network Pharmacology Analysis of ZiShenWan for Diabetic Nephropathy and Experimental Verification of Its Anti-Inflammatory Mechanism

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Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The inflammatory response plays a critical role in Diabetic nephropathy. ZiShenWan (ZSW) is a classical Chinese medicinal formula with remarkable clinical therapeutic effects on Diabetic nephropathy, but its pharmacological action mechanisms remain unclear.

In this study, a network pharmacology approach was applied to investigate the pharmacological mechanisms of ZiShenWan in Diabetic nephropathy therapy. Based on the results of network analysis, the core targets and signaling pathways related to anti-inflammatory effects were verified via experiments in cells.

The candidate chemical ingredients of ZiShenWan as well as its putative targets and known therapeutic targets of Diabetic nephropathy were acquired from appropriate databases. The “herb-ingredient-target” network for ZiShenWan in Diabetic nephropathy treatment was established.

A total of 56 active ingredients in ZiShenWan and 166 Diabetic nephropathy-related targets were selected from databases. A high proportion of core targets and top signaling pathways participate in inflammation. ZiShenWan markedly alleviated renal injuries pathologically and regulated related biomarkers. In particular, ZiShenWan significantly inhibited the exaggerated release of inflammatory cytokines as well as mitochondria (energy production) activation.

Conclusion: This study first comprehensively investigated the active ingredients, potential targets, and molecular mechanism of ZiShenWan as a therapy for Diabetic nephropathy. ZiShenWan achieved renoprotective effects in Diabetic nephropathy via regulation of multiple targets and signaling pathways, especially by alleviating inflammation. Results indicate that ZiShenWan is a promising multi-target therapeutic approach for Diabetic nephropathy treatment.

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