Cortex Dictamni extract induces apoptosis of activated hepatic stellate cells via STAT1 and attenuates liver fibrosis in mice
Cortex Dictamni extract induces apoptosis of activated hepatic stellate cells via STAT1 and attenuates liver fibrosis in mice
复制标题
白鲜皮提取物通过 STAT1 诱导活化的肝星状细胞凋亡并减轻小鼠肝纤维化
DOI：
10.1016/j.jep.2011.03.010
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发表时间：
2011-04-26
影响因子：
5.4
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Wu, Xing-Xin;Wu, Li-Mei;Xu, Qiang
民族药理学意义：白鲜皮用于治疗急性类风湿关节炎、皮肤炎、黄褐斑等多种炎症性疾病。目的：本研究旨在探讨白鲜皮乙醇提取物对肝纤维化的治疗作用及其可能的机制。材料和方法：通过测定四氯化碳(CCl(4))诱导的小鼠肝纤维化模型的组织学改变和胶原含量，评价白鲜皮提取物(CDE)的体内作用。结果：CDE可减轻CCl4诱导的小鼠肝纤维化，对活化的HSC-T6细胞活性的抑制作用明显强于正常肝细胞L02细胞。此外，CDE诱导HSC-T6细胞的凋亡与裂解的PARP和裂解的caspase-3表达增加有关。值得注意的是，CDE可激活HSC-T6细胞中的STAT1，JAK/STAT1信号抑制剂AG490可中和CDE对HSC-T6细胞凋亡的影响。结论：CDE通过激活STAT1选择性地诱导活化的HSC凋亡，具有抗纤维化作用，有望成为治疗肝纤维化的新策略。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
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 CCl(4)-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 CCl(4)-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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.