Study on the Effect of Rhubarb and Its Active Components on Pyroptosis in DKD by Regulating STAT3/Caspase-11 Axis

Abstract

Rhubarb has been found to have a certain protective effect on improving the kidney function. However, the specific mechanism is still unclear. In this study, network pharmacology, molecular docking spontaneous binding technology and molecular biology experiments were used to verify the mechanism of rhubarb and its active ingredients in the treatment of DKD. A total of 10 active compounds and 121 (larger than average) target proteins were collected. The target proteins with higher degree value were screened by PPI according to degree value as follows: AKT1, STAT3, EGFR, NFKB1, SRC, etc. GO and KEGG enrichment analysis suggest that rhubarb therapy for DKD mainly involves Pathways in cancer, Prostate cancer, Proteoglycans in cancer, Chemokine signaling pathway, PI3K-Akt signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, EGFR tyrosine kinase inhibitor resistance signaling pathway and so on. Furthermore, molecular docking results suggest that hydrogen bonding, salt bridge and hydrophobic interactions contribute to spontaneous binding of the compound to the target protein. Experimental verification shows that rhubarb and aloe emodin affect the mechanism of pyroptosis in diabetic kidney disease by regulating STAT3/Caspase11 axis. In conclusion, this study comprehensively elaborated the active compounds, potential targets and molecular experimental mechanisms of rhubarb to provide the basic experimental theory for clinical treatment of DKD.