Thymoquinone, a bioactive component of Nigella sativa Linn seeds or traditional spice, attenuates acute hepatic failure and blocks apoptosis via the MAPK signaling pathway in mice

Thymoquinone, a bioactive component of Nigella sativa Linn seeds or traditional spice, attenuates acute hepatic failure and blocks apoptosis via the MAPK signaling pathway in mice
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百里醌是黑种草种子或传统香料的生物活性成分,可通过 MAPK 信号通路减轻小鼠急性肝衰竭并阻止细胞凋亡

DOI:
10.1039/c4ra15065a
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发表时间:
2015
期刊:
影响因子:
3.9
通讯作者:
Nan Ji-Xing
Nan Ji-Xing
中科院分区:
化学3区
文献类型:
--
作者:
Yang Yong;Bai Ting;Sun Peng;Lian Li-Hua;Yao You-Li;Zheng Hui-Xing;Li Xin;Li Jin-Bin;Wu Yan-Ling;Nan Ji-Xing

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胸腺醌(Thymoquinone,TQ)是从黑种草子(Nigella sativa Linn)的黑孜然籽中提取的具有生物活性的天然产物,是一种广泛应用的香料或草药。在注射D-GalN(700 mg kg −1)/LPS(10 μg kg − 1)之前,对小鼠灌胃TQ(5或20 mg kg − 1)12 h和1 h,然后在用D-GalN/LPS处理后8 h处死。TQ预处理可降低D-GalN/LPS诱导的小鼠死亡率,逆转肝损伤。TQ减弱D-GalN/LPS诱导的肝细胞凋亡,这通过抑制caspase活化、PARP裂解和Bax/Bcl-2比率来证实。重要的是,TQ减弱了D-GalN/LPS介导的JNK,ERK和p38的磷酸化。此外,TQ抑制促炎细胞因子的产生。这些结果表明,TQ可以通过抑制caspase激活来调节D-GalN/LPS介导的急性肝衰竭,这与线粒体凋亡途径和MAPK信号通路一致。
Thymoquinone (TQ), a bioactive natural product obtained from the black cumin seeds of Nigella sativa Linn, is a widely used spice or herb. The present study investigated the hepatoprotective effect of TQ on acute hepatic failure induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice. The mice were intragastrically administrated TQ (5 or 20 mg kg−1) for 12 h and 1 h prior to D-GalN (700 mg kg−1)/LPS (10 μg kg−1) injections and then sacrificed 8 h after treatment with D-GalN/LPS. TQ pretreatment reduced the mortality induced by D-GalN/LPS and reversed liver damage. TQ attenuated D-GalN/LPS-induced hepatocyte apoptosis, which was confirmed by suppressing caspase activation, PARP cleavage and the Bax/Bcl-2 ratio. Importantly, TQ attenuated the D-GalN/LPS-mediated phosphorylation of JNK, ERK and p38. Furthermore, TQ suppressed the production of proinflammatory cytokines. These findings suggested that TQ could modulate D-GalN/LPS-mediated acute hepatic failure by inhibiting caspase activation, consistent with the mitochondrial pathway of apoptosis and the MAPK signaling pathway.
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