Medicine Research Center, Binzhou Medical University, Yantai 264003, China.
Biol Pharm Bull. 2011;34(3):343-8. doi: 10.1248/bpb.34.343.
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.
肝星状细胞(HSCs)在肝损伤时被激活,被定义为肝纤维化治疗的最重要靶点。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,这有助于减少这种细胞群体。用不同浓度的 RosA 处理不同时间后,HSC-T6 的增殖明显受到抑制。流式细胞术分析和透射电子显微镜(TEM)观察显示,RosA 处理的 HSC-T6 呈时间依赖性凋亡,并在细胞中显示出典型的凋亡特征。信号转导和转录激活因子 3(STAT3)的磷酸化,调节各种组织中的细胞存活、增殖和分化,通过 Western blot 分析明显降低,与细胞周期蛋白 D1 和 B 细胞淋巴瘤/白血病-2(Bcl-2)的下调相关。总之,这些结果表明,RosA 能够抑制 HSC-T6 的增殖并诱导其凋亡,部分原因是抑制了 STAT3 的磷酸化,有助于逆转肝纤维化。