Quantitative Crotonylome Analysis Reveals the Mechanism of Shenkang Injection on Diabetic Nephropathy

Shenkang injection (SKI) has been widely used in the clinical treatment of chronic kidney diseases in China because of its efficacy and safety. However, the underlying mechanism of SKI in diabetic nephropathy (DN) remains unclear. The present study aimed to investigate the renoprotective effects and possible mechanisms of SKI in diabetic db/db mice. We showed that SKI ameliorated hyperglycemia and abnormal renal biochemical parameters in db/db mice. Crotonylome and subsequent bioinformatics analyses indicated that the molecular functions of the significantly different crotonylated proteins regulated by SKI were closely related to oxidoreductase activity and oxidative phosphorylation might be one of the main pathways through which SKI functions in DN. Subsequent PRM validation of the selected crotonylated proteins confirmed these findings. In addition, we determined that SKI could regulate the expression of specific proteins in oxidative phosphorylation complexes and enhance antioxidant capacity. Taken together, our data suggest that SKI exerted the protective effect against DN potentially through reversing the abnormal crotonylation expression of oxidoreductase-related proteins.