Cortex Dictamni extract induces apoptosis of activated hepatic stellate cells via STAT1 and attenuates liver fibrosis in mice
2011
Wu, Xing-Xin | Wu, Li-Mei | Fan, Jing-Jing | Qin, Yu | Chen, Gong | Wu, Xue-Feng | Shen, Yan | Sun, Yang | Xu, Qiang
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicines, Cortex Dictamni is prescribed for the treatment of a variety of inflammatory diseases such as acute rheumatoid arthritis, skin inflammation and jaundice. AIM OF THE STUDY: This study was designed to investigate the effect of ethanol extract of Cortex Dictamni on treatment of hepatic fibrosis and its possible mechanisms. MATERIALS AND METHODS: The in vivo effect of Cortex Dictamni extract (CDE) was evaluated by measuring histological changes and collagen content in CCl₄-indcued hepatic fibrosis mice. Viability, apoptosis and protein expression of hepatic stellate cells (HSC) were analyzed by MTT, Annexin V staining and Western blot respectively. RESULTS: CDE alleviated CCl₄-induced hepatic fibrosis in mice and showed a much stronger inhibition of cell viability in activated HSC cell line HSC-T6 than that in normal hepatocyte L02 cells. Furthermore, CDE induced apoptosis of HSC-T6 cells associated with increased expressions of cleaved PARP and cleaved caspase-3. Interestingly, CDE activated STAT1 in HSC-T6 cells and the effect of CDE on apoptosis of HSC-T6 cells could be neutralized using JAK/STAT1 signaling inhibitor AG490. CONCLUSIONS: These findings suggest that CDE possesses anti-fibrosis activity with selectively induction of activated HSC apoptosis via activating STAT1, which might be a novel strategy for hepatic fibrosis therapy.
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