Effect of Sedum sarmentosum BUNGE Extract on Aristolochic Acid–Induced Renal Tubular Epithelial Cell Injury

Journal of Pharmacological Sciences

Hong Lu³  Bicheng Chen²  Dan Hong¹  Linchao Ding¹  Yongheng Bai²  Liping Hu³ 

[1] School of Laboratory Medicine and Life Science, Wenzhou Medical University, China;Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, China;Department of Laboratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, China

关键词: aristolochic acid;    epithelial-to-mesenchymal transition;    renal fibrosis;    Sedum sarmentosum Bunge;    inflammation;   

DOI  :  10.1254/jphs.13216FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(41)Cited-By(2)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.

【 授权许可】

Unknown