Abstract
Hepatic fibrosis is one of the critical steps contained in the pathogenesis of liver cirrhosis. Excessive deposition of collagen contributes to the development of fibrosis in chronic liver injury. Activation of hepatic stellate cells (HSCs) plays an important role in fibrogenesis and is accountable for providing extracellular matrix components. The berry of Schisandra chinensishas been known to exert hepatoprotective properties. However, its effect on HSCs is not completely understood. Therefore, in this study, we investigated the inhibitory effect of its ethanolic extract (SBE) on hepatic fibrogenesis. We found that SBE treatment effectively reduced the serum levels of alanine aminotransferase and aspartate aminotransferase as well as collagen deposition in the hepatic parenchyma in a thioacetamide-induced hepatic fibrosis mouse model. Moreover, SBE inhibited transforming growth factor β (TGFβ)-induced mRNA expression of α-smooth muscle actin (αSMA) and collagen type 1 α1 (COL1A1) in HSCs, suggesting that SBE exerts anti-fibrotic activity by attenuating TGFβ-induced HSC activation. To identify the active components of SBE accountable for HSC inhibition, SBE was further partitioned based on the hydrophobicity of the solvents such as water, n-butanol, ethyl acetate, chloroform, and n-hexane. The n-hexane fraction was selected and further separated using analytical high-performance liquid chromatography. We found that six lignans contained in the n-hexane fraction strongly reduced TGFβ-induced expression of both αSMA and COL1A1 mRNA. These data suggest that at least six lignans contained in SBE have the strong potential to prevent TGFβ-induced HSC activation.
KeywordsAlpha-smooth muscle actin Collagen type 1 α1 Hepatic fibrosis Hepatic stellate cells Schisandra Transforming growth factor β
… TGFβ was purchased from R&D Systems (Minneapolis, MN, USA). Lignans
including
gomisin D,
gomisin G,
gomisin H,
gomisin J,
gomisin N,
gomisin
O,
angeloylgomisin H,
angeloylgomisin O, and
benzoylgomisin O were
purchased from Chengdu
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