Elucidating the Mechanism of Jisheng Shenqi Pills in the Treatment of Diabetic Kidney Disease: Network Pharmacology Combined with Experimental Verification.

Abstract

While the annual incidence of diabetic kidney disease (DKD) has been soaring, the exact mechanisms underlying its onset and progression remain partially understood. The present study delved into the underlying mechanisms of Jisheng Shenqi Pill (JSP) in the treatment of DKD. The active constituents and prospective targets of JSP were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), while DKD-associated disease targets were obtained from the GeneCards database. Subsequently, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to assess the overlapping segment of drugs and disease targets. Meanwhile, a component-target-pathway network was constructed to identify pivotal components, targets, and pathways. Molecular docking and molecular dynamics simulation were also carried out to validate the binding efficacy of the pivotal components with the targets. Finally, animal experiments were conducted to corroborate the efficacy of the aforementioned targets and pathways. According to bioinformatics analysis, the primary targets included JUN, TNF, and BAX, while the pivotal pathways involved were AGE/RAGE and PI3K/AKT signaling cascades. In vivo experiments demonstrated that JSP effectively mitigated renal impairment in DKD by reducing renal inflammation and apoptosis. This effect was presumably achieved by modulating the AGERAGE axis and the PI3K/AKT signaling pathway. Our findings imply that JSP could ameliorate renal inflammation and apoptosis in DKD mice by modulating the AGE/RAGE axis and the PI3K/AKT signaling pathway. These findings provide valuable insights into traditional Chinese medicine-based treatments for DKD.