Anti-fibrotic effect of wogonin in renal tubular epithelial cells via Smad3-dependent mechanisms

Renal fibrosis, a common feature and leading cause for End Stage Renal Disease, still lacks effective therapy. In the current study, we detected and compared the anti-fibrotic effects of wogonin and wogonoside, two major components of Scutellaria baicalensis Georgi, in TGF-beta 1-treated tubular epithelial cells of human and murine origins. Results consistently showed that compared with wogonoside, wogonin inhibits TGF-beta 1-induced upregulated mRNA and protein levels of collagen I and alpha-SMA with more efficiency, which was further confirmed by the immunofluorescence results that wogonin decreased the percentage of collagen I and alpha-SMA positive cells in TGF-beta 1-treated tubular epithelial cells. Mechan-istically, wogonin mainly decreased Smad3 phosphorylation, but had marginal effect on non-canonical TGF-beta signaling pathways, such as p38 and ERIC MAP Kinase. Furthermore, in the cells deficient for TGF-beta signaling or downstream Smad3, results demonstrated that even high concentration of wogonin failed to further decrease the level of collagen I and alpha-SMA, indicating the essential role of TGF-beta/Smad3 signaling inhibition in the therapeutic action of wogonin in TGF-beta 1-stimulated tubular epithelial cells. Collectively, our results indicated that wogonin may be utilized as a potential anti-fibrotic Traditional Chinese Medicine monomer in the treatment of renal fibrosis. (C) 2016 Elsevier B.V. All rights reserved.