title: Effect of Sedum sarmentosum BUNGE extract on aristolochic acid-induced renal tubular epithelial cell injury.
abstract: 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.
authors.affiliation: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, China.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Bai
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Liping
authors.initials: L
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Hong
authors.forename: Linchao
authors.initials: L
authors.lastname: Ding
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D034341:Aristolochic Acids / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D007249:Inflammation; D007684:Kidney Tubules / Q000166:cytology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D031963:Sedum; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; D009153:Mutagens; D010936:Plant Extracts; D019716:Tissue Inhibitor of Metalloproteinase-2; C000228:aristolochic acid I; D020778:Matrix Metalloproteinase 2