Potent effects of dioscin against liver fibrosis.

Abstract

We previously reported the promising effects of dioscin against liver injury, but its effect on liver fibrosis remains unknown. The present work investigated the activities of dioscin against liver fibrosis and the underlying molecular mechanisms. Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2 and primary rat hepatic stellate cells (HSCs), but not hepatocytes. Furthermore, dioscin markedly increased peroxisome proliferator activated receptor-γ (PPAR-γ) expression and significantly reduced a-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen α1 (I) (COL1A1) and collagen α1 (III) (COL3A1) levels in vitro. Notably, dioscin inhibited HSCs activation and induced apoptosis in activated HSCs. In vivo, dioscin significantly improved body weight and hydroxylproline, laminin, α-SMA, TGF-β1, COL1A1 and COL3A1 levels, which were confirmed by histopathological assays. Dioscin facilitated matrix degradation, and exhibited hepatoprotective effects through the attenuation of oxidative stress and inflammation, in addition to exerting anti-fibrotic effects through the modulation of the TGF-β1/Smad, Wnt/β-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial signaling pathways, which triggered the senescence of activated HSCs. In conclusion, dioscin exhibited potent effects against liver fibrosis through the modulation of multiple targets and signaling pathways and should be developed as a novel candidate for the treatment of liver fibrosis in the future.

• Authors: Xiaoling Zhang, Xu Han, Lianhong Yin, Lina Xu, Yan Qi, Youwei Xu, Huijun Sun, Yuan Lin, Kexin Liu, Jinyong Peng
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 9713 (Apr 08 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25853178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Smad Proteins
• Tissue Inhibitor of Metalloproteinases
• Transforming Growth Factor beta
• dioscin
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinases
• Diosgenin

Topics

• Animals
• Apoptosis (drug effects)
• Cellular Senescence (drug effects)
• Diosgenin (administration & dosage, analogs & derivatives, pharmacology)
• Extracellular Matrix (metabolism)
• Hepatic Stellate Cells (drug effects, metabolism)
• Hepatocytes (drug effects, metabolism)
• Liver Cirrhosis (drug therapy, etiology, metabolism, pathology)
• Male
• Matrix Metalloproteinases (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Signal Transduction (drug effects)
• Smad Proteins (metabolism)
• Tissue Inhibitor of Metalloproteinases (metabolism)
• Transforming Growth Factor beta (metabolism)
• Wnt Signaling Pathway (drug effects)