Demethylbellidifolin inhibits proliferation and activation of hepatic stellate cells

The effects of demethylbellidifolin (DMB), a xanthone compound extracted from Swertia davidi Franch, on activation of hepatic stellate cells (HSC) were investigated. Rat HSC line HSC-T6 cultured in vitro showed an activated status, which expressed α-smooth muscle actin (α-SMA) and synthesized collagen I. Treated with different concentrations (10, 20, or 40 μM) of DMB for 12 -48 hr could markedly inhibit cell proliferation reflected by MTT and [(3)H]thymidine incorporation assays, and downregulate the expressions of both α-SMA and collagen I in HSC-T6 cells. Also, such treatment concentration-dependently downregulated both mRNA and protein expressions of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF). The expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) was very low in activated HSC-T6, which could be significantly upregulated by treatment with DMB. Furthermore, PPAR-γ antagonist PD68235 (5-20 μM) markedly blocked these effects of DMB mentioned above. In summary, DMB inhibits HSC proliferation and activation, which may be related to activating PPAR-γ-mediated pathway.