Madecassoside Improves Renal Injury via Activation of AMPK/Autophagy in Experimental Membranous Nephropathy

Currently, membranous nephropathy (MN) has received considerable attention in Chine due to its increasing prevalence and limited therapeutic approaches. Madecassoside (MA) is a natural compound with anti-inflammatory, antioxidant, anticancer, and wound healing effects. In this study, we aimed to investigate the roles and related mechanisms of MA in MN. The passive Heymann nephritis (PHN) model was established in rats to mimic human MN. MA was intraperitoneally injected into MN rats beginning 1 week after modeling for 4 weeks. Urine, blood samples, and kidney samples were collected for biochemical analysis and histopathological analysis. Western blot analysis and immunofluorescence staining were performed. MA relieved MN-induced renal dysfunctions and histopathology in rats. Additionally, MA reduced IgG and C3 deposition and alleviated podocyte injury in MN rats. Moreover, MA activated canonical autophagy by modulating AMPK/mTOR. Furthermore, MA ameliorated oxidative stress and inflammation in renal tissues of MN model rats. In conclusion, treatment with MA ameliorates proteinuria and renal dysfunctions in MN rats by activating AMPK/mTOR-mediated autophagy.