Nodakenin alleviated obstructive nephropathy through blunting Snail1 induced fibrosis.
Tubulointerstitial fibrosis plays an important role in end-stage renal failure, and there are only limited therapeutic options available to preserve organ function. In the present study, we identified that nodakenin, a coumarin isolated from the roots of Angelicae gigas, functions effectively against unilateral ureteral obstruction (UUO)-induced fibrosis via down-regulating Snail1 expression. We established UUO-induced renal fibrosis in mice and then administered with nodakenin orally ata a dose of 1 and 10 mg/kg. The in-vivo results indicated that nodakenin protected obstructive nephropathy through its anti-inflammatory and anti-fibrotic properties. Nodakenin prevented the infiltration of inflammatory cells, alleviated the levels of pro-inflammatory cytokines, reduced the polarization of macrophages and down-regulating the aberrant deposition of extracellular matrix at the site of injury. Of note, nodakenin dramatically impeded Smad3, NF-κB p65 phosphorylation and Snail1 expression. In line with in vivo studies, nodakenin suppressed the expression of Snail1, Smad3 phosphorylation and fibrogenesis in TGF-β1-treated renal epithelial cells in-vitro. Furthermore, we found that the effect of nodaknin against fibrosis was reversed in Snail1 overexpressing cells, whereas nodakenin could not further reduce expression of fibrogenesis in Snail1 silenced cells, suggesting that nodaknein may function through a Snail1-dependent manner. Collectively, this study reveal a critical role of nodakenin in the cure of renal fibrosis.
['Li|Jianchun|J|', 'Wang|Lu|L|', 'Tan|Ruizhi|R|', 'Zhao|Sha|S|', 'Zhong|Xia|X|', 'Wang|Li|L|0000-0003-3881-3149']
D029969:Angelica D000818:Animals D000893:Anti-Inflammatory Agents D003374:Coumarins D004195:Disease Models, Animal D005355:Fibrosis D005786:Gene Expression Regulation D005960:Glucosides D006801:Humans D007668:Kidney D007676:Kidney Failure, Chronic D008264:Macrophages D051379:Mice D016328:NF-kappa B D010766:Phosphorylation D018517:Plant Roots D015398:Signal Transduction D051900:Smad3 Protein D000071250:Snail Family Transcription Factors D053773:Transforming Growth Factor beta1 D014517:Ureteral Obstruction
Nodakenin Snail1 renal fibrosis inflammation