Rosmarinic acid inhibits proliferation and induces apoptosis of hepatic stellate cells.
Rosmarinic acid inhibits proliferation and induces apoptosis of hepatic stellate cells.
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DOI：
10.1248/bpb.34.343
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发表时间：
2011-03
影响因子：
2
通讯作者：
Jin-jin Zhang;Youlei Wang;Xue-bin Feng;Xiao-dong Song;Wen-bo Liu
中科院分区：
文献类型：
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作者：
Jin-jin Zhang;Youlei Wang;Xue-bin Feng;Xiao-dong Song;Wen-bo Liu
肝星状细胞（hepatic stellate cells，HSCs）是肝纤维化治疗中最重要的靶点，在肝损伤过程中被激活。在本研究中，我们评估了迷迭香酸（RosA）对活化的肝星状细胞（HSC-T6）增殖和凋亡的影响，这有助于减少该细胞群体。不同浓度的RosA作用HSC-T6细胞不同时间后，HSC-T6细胞增殖均受到明显抑制。流式细胞仪分析和透射电镜观察显示，RosA处理后HSC-T6细胞发生凋亡，并呈现出典型的凋亡特征。蛋白质印迹分析结果显示，在多种组织中调节细胞存活、增殖和分化的信号转导和转录激活蛋白-3（STAT 3）的磷酸化水平显著降低，并且与CyclinD 1和B细胞淋巴瘤/白血病-2（Bcl-2）的下调相关。综上所述，这些结果表明，RosA能够抑制HSC-T6的增殖并诱导凋亡，部分原因是抑制了STAT 3的磷酸化，这有助于逆转肝纤维化。
Hepatic stellate cells (HSCs), activated during liver injury, are defined as the most important target in the therapy of hepatic fibrosis. In the present study, we evaluated the effect of Rosmarinic acid (RosA) on the proliferation and apoptosis in activated hepatic stellate cells (HSC-T6), which is useful to decrease this cell population. The proliferation of HSC-T6 was significantly inhibited after treated with various concentrations of RosA for different times. Flow cytometric analyses and transmission electron microscope (TEM) observations revealed that HSC-T6 treated with RosA underwent apoptosis in a time dependent manner and displayed typical apoptotic features in the cells. The phosphorylation in signal transducer and activator of transcription protein-3 (STAT3), which regulates cell survival, proliferation and differentiation in a variety of tissues, was markedly decreased as the result of Western blot assay and correlated with downregulation of CyclinD1 and B cell lymphoma/leukemia-2 (Bcl-2). In conclusion, these results suggested that RosA was able to inhibit proliferation and induce apoptosis in HSC-T6, partly due to the inhibition of phosphorylation in STAT3, which contributed to the reversal of hepatic fibrosis.