Mechanism of Rhubarb for Diabetic Kidney Disease through the AMPK/NF-kappa B Signaling Pathway Based on Network Pharmacology

摘要

Rhubarb (Da-huang in pinyin, Radix Rhei Et Rhizome in pharmaceutical name) is a heat-clearing and laxative herbal medicine, which is widely used to treat diabetic kidney disease in China. The study aims to decrypt the underlying mechanisms of the treatment of diabetic kidney disease using a systems pharmacology approach. Active compounds and corresponding potential therapeutic targets were harvested by utilizing the database of TCMSP. DKD targets were adopted from DrugBank, OMIM, TTD, and GAD databases. Then a network of Rhubarb- compounds - target - DKD network was harvested. The PPI network was then generated by the String database and subjected to Cytoscape software to harvest major and core targets network by topological analysis. Genes from the core targets network were further subjected to GO and KEGG enrichment analysis to figure out potential targeting pathways. Human podocyte cells (HPC) were used to further investigate the mechanism of against DKD. A total of 6 active ingredients and 271 targets of Rhubarb were picked out. 11 cellular biological processes and 18 pathways of mostly associated with inflammatory response, apoptosis, fibrosis, and peripheral circulation. Moreover, experimental validation suggests that Rhubarb increased cell viability. Rhubarb extract significantly suppressed the expression of NF-kappa B, Bcl-2, Caspase-3, and Cleaved Caspase-3, promoted the expression of AMPK and Bax, and decreased the release of cytokines. Rhubarb could alleviate DKD via the molecular mechanisms predicted by network pharmacology.