Hepatoprotective properties of sesamin against CCl4 induced oxidative stress-mediated apoptosis in mice via JNK pathway
Hepatoprotective properties of sesamin against CCl4 induced oxidative stress-mediated apoptosis in mice via JNK pathway
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DOI：
10.1016/j.fct.2013.11.017
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发表时间：
2014-02-01
影响因子：
4.3
通讯作者：
Liu, Chan-Min
中科院分区：
文献类型：
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作者：
Ma, Jie-Qiong;Ding, Jie;Liu, Chan-Min
芝麻素 (Ses) 是从芝麻中提取的主要木酚素之一，据报道具有许多益处和药用特性。然而，其对四氯化碳（CCl4）引起的肝损伤的保护作用尚未阐明。本研究的目的是探讨芝麻素对暴露于 CCl4 的小鼠氧化应激和细胞凋亡的保肝作用。我们的数据表明，芝麻素以剂量依赖的方式显着预防 CCl4 诱导的肝毒性，肝损伤的诊断指标（血清转氨酶活性）和组织病理学都表明了这一点。分析。此外，CCl4 诱导的活性氧 (ROS) 产生和氧化应激显着升高，通过脂质过氧化水平增加和肝脏总抗氧化能力 (TAC) 消耗来证明，芝麻素治疗可抑制 CCl4 诱导的活性氧 (ROS) 产生和氧化应激的显着升高。此外，TUNEL实验表明，芝麻素显着抑制CCl4诱导的小鼠肝脏细胞凋亡。在探索芝麻素作用的潜在机制时，我们发现用芝麻素处理 CCl4 处理小鼠的肝脏中 caspase-3 的活性明显受到抑制。芝麻素增加肝脏中磷酸化 Jun N 末端激酶 (INK) 的表达水平，进而使促凋亡信号事件失活，恢复线粒体促凋亡和抗凋亡 Bcl-2 蛋白之间的平衡，并减少 CCl4 处理小鼠肝脏中线粒体细胞色素 c 的释放。 INK 还通过调节磷酸化 c-Jun 蛋白、坏死因子-α (TNF-α) 和 Bak 的表达水平，参与芝麻素对 CCl4 诱导的肝损伤的线粒体外源性凋亡途径。总之，这些结果表明芝麻素对 CCl4 诱导的细胞凋亡的抑制至少部分归因于其抗氧化活性及其调节 JNK 信号通路的能力。 (C) 2013 Elsevier Ltd. 保留所有权利。
Sesamin (Ses), one of the major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced injury in liver have not been clarified. The aim of the present study was to investigate the hepatoprotective effects of sesamin on oxidative stress and apoptosis in mice exposed to CCl4. Our data showed that sesamin significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological. analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) in liver, were suppressed by treatment with sesamin. Furthermore, TUNEL assay showed that CCl4-induced apoptosis in mouse liver was significantly inhibited by sesamin. In exploring the underlying mechanisms of sesamin action, we found that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of CCl4 treated mice. Sesamin increased expression levels of phosphorylated Jun N-terminal kinases (INK) in liver, which in turn inactivated pro-apoptotic signaling events restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 proteins and decreasing the release of mitochondrial cytochrome c in liver of CCl4 treated mice. INK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against CCl4 induced liver injury by regulating the expression levels of phosphorylated c-Jun proteins, necrosis factor-alpha (TNF-alpha) and Bak. In conclusion, these results suggested that the inhibition of CCl4-induced apoptosis by sesamin is due at least in part to its anti-oxidant activity and its ability to modulate the JNK signaling pathway. (C) 2013 Elsevier Ltd. All rights reserved.