Suchilactone ameliorates podocyte injury in membranous nephropathy by modulating the JNK/p38 MAPK pathway in vitro.

Membranous nephropathy (MN) represents an autoimmune glomerular condition fundamentally marked by immune complex accumulation and complement initiation. About 20 to 30 percent of patients go on to develop chronic kidney disease. Current immunosuppressive treatment regimens frequently possess considerable potential toxicity, necessitating the development of more effective and safer therapeutic alternatives. Suchilactone (Suc) is a newly found compound with potential effects against inflammation, but its function in MN remains unreported. The MN model in podocytes utilizing serum activated by zymosan A was established. The impact of Suc on cell viability was confirmed through the CCK8 assay. A transcriptomic analysis was performed to clarify the mechanism of action of Suc in MN. Pharmacological experiments utilizing Western blot, quantitative real-time PCR, and immunofluorescence were performed to corroborate transcriptomic results. We assessed the abundance of key podocyte proteins, inflammatory markers, and components of intracellular signaling pathways. To further elucidate the connection between MAPK and Suc in MN, we employed specific inhibitors in our experimental approach. It was demonstrated that Suc markedly protected podocytes by suppressing the expression of inflammatory cytokines TNF-α and IL-1β, inhibiting the inflammatory pathway protein p65, reversing the decline of nephrin and podocin-critical podocyte proteins-and reducing C5b-9 release. This process fixed damage to podocytes to keep the glomerular filtration barrier integrity. Experiments on transcriptomics and intracellular pathways showed that the JNK/p38 MAPK pathway contribute to these effects. In conclusion, Suc can protect podocytes from complement-mediated injury and reduce inflammation through the JNK/p38 MAPK pathway to ameliorates complement-mediated podocyte injury in MN.