title: Astragaloside IV from Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-кB in vivo and in vitro.
abstract: Renal fibrosis is characterized by infiltration of inflammatory cells, activation and proliferation of fibroblasts, and accumulation of extracellular matrix (ECM). Astragalus membranaceus (AM) is traditional Chinese medicine and has a range of pharmacological effects. Astragaloside IV (As IV) is the main compound of AM and has anti-inflammation activities. Whether As IV ameliorates renal interstitial fibrosis by inhibiting inflammation remains unknown. Accordingly, this study investigated the ameliorating effect of As IV on renal fibrosis. Renal fibrosis was induced in vivo using the unilateral ureteral obstruction (UUO) model. UUO mice were administered intragastrically with As IV (20 and 40mg/kg/day). After a week, ECM including fibronectin and collagen I was examined by Immunohistochemistry and Western blot, inflammatory cells (CD68 and CD3) were detected by Immunohistochemistry, the release of inflammatory cytokines (tumor necrosis factor-α and interleukin-1β) was inspected by polymerase chain reaction, and signaling pathway was determined by Western blot. In vitro, 100ng/ml lipopolysaccharide (LPS) stimulated epithelial cells to construct the inflammatory model; these cells were treated by As IV (10 and 20μM) with or without TAK-242 (1μM) for 48h. The released inflammatory cytokines were assayed by enzyme-linked immunosorbent assay, and signaling pathway was evaluated by Western blot. As IV decreased accumulation of ECM and infiltration of inflammatory cells in UUO-induced renal fibrosis. Furthermore, As IV markedly attenuated pro-inflammatory cytokines in UUO mouse and LPS-induced epithelial cells. As IV also inhibited the TLR4 and nuclear factor (NF)-кB signaling pathway in vivo and vitro. These results demonstrate that As IV protects against the progression of renal fibrosis by inhibiting inflammation via the TLR4/NF-кB signaling pathway.
authors.affiliation: Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Xinbo
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Congbo
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Hubei, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Shan
authors.affiliation: Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei, China. Electronic address: yymcyqs@126.com.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D027885:Astragalus propinquus / Q000276:immunology*; D002460:Cell Line; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D012503:Saponins / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014315:Triterpenes / Q000627:therapeutic use*; D014517:Ureteral Obstruction / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D012503:Saponins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014315:Triterpenes; C052064:astragaloside A
keywords: Astragaloside IV; Astragalus membranaceus; Inflammation; Renal interstitial fibrosis