title: Demethylbellidifolin inhibits proliferation and activation of hepatic 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 [(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.
authors.affiliation: 1XiangYa Hospital, Chang Sha, China.
authors.forename: Jun Fu
authors.initials: JF
authors.lastname: Li
authors.forename: Gen Fang
authors.initials: GF
authors.lastname: Lu
authors.forename: You Yi
authors.initials: YY
authors.lastname: Zou
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023421:Models, Animal; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000199:Actins; D024042:Collagen Type I; D055513:Connective Tissue Growth Factor; D047495:PPAR gamma; D053773:Transforming Growth Factor beta1; D014966:Xanthenes; D044004:Xanthones; C467829:demethylbellidifolin; C498862:Acta2 protein, rat