Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells
Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells
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百里醌通过激活的肝星状细胞中的 PI3K 和 TLR4 信号通路减轻肝纤维化
DOI：
10.1016/j.intimp.2012.12.020
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发表时间：
2013-02-01
影响因子：
5.6
通讯作者：
Nan, Ji-Xing
中科院分区：
文献类型：
--
作者：
Bai, Ting;Lian, Li-Hua;Nan, Ji-Xing
百里醌（TQ）是从药用植物黑种草中提取的主要活性化合物。在本研究中，我们探讨了TQ在脂多糖（LPS）激活的大鼠肝星状细胞系T - HSC/Cl - 6中的抗纤维化机制。在给予LPS（1μg/ml）之前，用TQ（3.125、6.25和12.5μM）处理T - HSC/Cl - 6细胞。我们的数据表明，TQ有效降低了激活的T - HSC/Cl - 6细胞的活力。TQ显著减弱了CD14和Toll样受体4（TLR4）的表达。TQ还显著抑制磷脂酰肌醇3 - 激酶（PI3K）和丝氨酸/苏氨酸激酶 - 蛋白激酶B（Ala）的磷酸化。TQ使α - 平滑肌肌动蛋白（α - SMA）和I型胶原蛋白（collagen - I）的表达显著降低。此外，TQ降低了X连锁凋亡抑制蛋白（XIAP）和细胞型Fas相关死亡结构域样白细胞介素-1β转换酶抑制蛋白（cellular FLIP，c - FLIPL）的表达，这与细胞凋亡的调节有关。此外，TQ显著提高了D - 半乳糖胺（D - GlaN）致敏小鼠抵抗LPS攻击的存活率，并降低了血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平，这与体外实验结果一致。我们的数据表明，TQ部分通过阻断激活的肝星状细胞上的TLR4表达和PI3K磷酸化来减轻肝纤维化。因此，TQ可能是治疗肝纤维化的潜在候选药物。（C）2013爱思唯尔公司。保留所有权利。
Thymoquinone (TQ) is the major active compound derived from the medicinal Nigella sativa. In the present study, we investigated the anti-fibrotic mechanism of TQ in lipopolysaccharide (LPS)-activated rat hepatic stellate cells line, T-HSC/Cl-6. T-HSC/Cl-6 cells were treated with TQ (3.125, 6.25 and 12.5 mu M) prior to LPS (1 mu g/ml). Our data demonstrated that TQ effectively decreased activated T-HSC/Cl-6 cell viability. TQ significantly attenuated the expression of CD14 and Toll-like receptor 4 (TLR4). TQ also significantly inhibited phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Ala) phosphorylation. The expression of alpha-SMA and collagen-I were significantly decreased by TQ. Furthermore, TQ decreased X linked inhibitor of apoptosis (XIAP) and cellular FLIP (c-FLIPL) expression, which are related with the regulation of apoptosis. Furthermore, TQ significantly increased the survival against LPS challenge in D-galactosamine (D-GlaN)-sensitized mice, and decreased the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were in line with in vitro results. Our data demonstrated that TQ attenuates liver fibrosis partially via blocking TLR4 expression and PI3K phosphorylation on the activated HSCs. Therefore, TQ may be a potential candidate for the therapy of hepatic fibrosis. (C) 2013 Elsevier B.V. All rights reserved.