Effect of Sedum sarmentosum BUNGE extract on aristolochic acid-induced renal tubular epithelial cell injury

Aristolochic acid (aa) is known as a potent mutagen that induces significant cytotoxic and mutagenic effects on renal tubular epithelial cells. clinically,the persistent injury of aa results in the infiltration of inflammatory cells,epithelial-to-mesenchymal transition (emt),and renal tubulointerstitial fibrosis. there are no truly effective pharmaceuticals. in this study,we investigated the potential role of the extract of sedum sarmentosum bunge (ssb),a traditional chinese herbal medicine,on rat tubuloepithelial (nrk-52e) cells after aa injury in vitro. evidence revealed that aa induced mitochondrial-pathway-mediated cellular apoptosis,accompanied by cell proliferation in a feedback mechanism. treatment with ssb also induced cells to enter early apoptosis,but inhibited cell proliferation. in cultured nrk-52e cells,aa induced the imbalance of mmp-2/timp-2 and promoted emt and ecm accumulation. ssb treatment significantly alleviated aa-induced nrk-52e cells fibrosis-like appearance,inhibited the induction of emt,and deposition of ecm. ssb also decreased the activity of the nf-κb signaling pathway,resulting in down-regulated expression of nf-κb-controlled chemokines and pro-inflammatory cytokines,including mcp-1,mif,and m-csf,which may regulate the macrophage-mediated inflammatory reaction during renal fibrosis in vivo. therefore,these findings suggest that ssb exerts protective effects against aa-induced tubular epithelial cells injury through suppressing the synthesis of inflammatory factors,emt,and ecm production. © the japanese pharmacological society.