The inhibition of hepatic stellate cell (HSC) proliferation has been considered as an effective therapeutic target for the treatment of liver fibrosis.
METHODS AND RESULTS:
The methanolic extract of Liriodendron tulipifera showed significant inhibitory activity against the proliferation of HSCs. Bioactivity-guided isolation afforded twelve compounds including (-)-sesamin (1), (-)-syringaresinol (2), (+)-Dihydrodehydrodiconiferyl alcohol (3), salvinal (4), (+)-guaiacylglycerol-8-O-4'-dihydroconiferyl ether (5), (±)-guaiacylglycerol-8-O-4'-sinapyl alcohol ether (6), tanegool (7), (+)-5,5'-dimethoxy-7-oxolariciresinol (8), 3-hydroxy-4-methoxyacetophenone (9), 4-acetoxymethylphenol (10), (-)-paramicholide (11), and blumenol A (12). Among the compounds isolated, 2, 3 and 4 significantly attenuated the proliferation of the activated HSC-T6 cells. The maximal dose of these compounds, however, showed no cytotoxicity in primary cultured rat hepatocytes. Collagen deposition in the activated HSC-T6 cells was reduced by 2, 3 and 4. Also, the increased production of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α induced by lipopolysaccharide was decreased by 3 and 4 in RAW264.7 macrophage cells. Collectively, (-)-syringaresinol (2), (+)-Dihydrodehydrodiconiferyl alcohol (3), and salvinal (4) isolated from L. tulipifera leaves and twigs exhibited selective antifibrotic activities toward the activated HSCs and suppressed TNF-α production in RAW264.7 macrophages.
CONCLUSIONS:
These compounds may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis. |
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