A Network Pharmacology Approach to Understand the Action Mechanisms of the TangShenKangPing Decoction for Diabetic Nephropathy Treatment

Background: TangShenKangPing decoction (TSKPD) has been used to treat patients with diabetic nephropathy (DN) for more than 10 years. However, its active ingredients and their pharmacological mechanisms of action remain unclear. In this study, we aimed to identify the key targets, major active ingredients, and pathways of TSKPD using network pharmacology. Methods: Human phenotypic disease, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed and 37 candidates targets of 40 active TSKPD ingredients were identified. Enrichment analyses revealed that TSKPD reduced podocyte apoptosis via vitamin metabolic processes, regulated the inflammatory response via the advanced glycation end product–receptor for AGE (AGE-RAGE) signaling, and reduced abnormal angiogenesis via vascular endothelial growth factor (VEGF) signaling in patients with DN. Furthermore, we verified the therapeutic roles and action mechanism of TSKPD in db/db mice with DN. The medicine was administered via gavage for 12 weeks. Fasting blood glucose, blood lipid, pro-inflammatory cytokine, and 24 h urinary albumin levels and pathological alterations in the renal tissues were evaluated. KHDRBS1, NLRP3 and VEGF relative mRNA and protein expression levels in renal tissues were determined using reverse transcription-quantitative olymerase chain reaction (RT-qPCR) and western blotting, respectively. Results: Treatment with TSKPD decreased proteinuria and lipid levels in the serum, significantly decreased the kidney weight, ameliorated renal histopathological alterations, and reduced pro-inflammatory cytokine expression and oxidative stress in db/db mice. Conclusion: TSKPD exerts therapeutic effects by regulating multiple factors, reducing oxidative stress and inflammation, and protecting the podocytes.