Demethylbellidifolin Inhibits Proliferation and Activation ofHepatic Stellate Cells

ABSTRACT

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 [³H]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.

Keywords: :

• demethylbellidifolin
• hepatic stellate cell
• transforming growth factor-β1
• peroxisome proliferator-activated receptor-γ
• Swertia davidi
• gentianaceae

ACKNOWLEDGMENT

This work was supported by a grant from Provincial Health Administration (B2006-090), Hunan, China.

Declaration of Interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.