Activation of Nrf2 protects against triptolide-induced hepatotoxicity.
Activation of Nrf2 protects against triptolide-induced hepatotoxicity.
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Nrf2 的激活可防止雷公藤甲素诱发的肝毒性
DOI：
10.1371/journal.pone.0100685
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Li J;Shen F;Guan C;Wang W;Sun X;Fu X;Huang M;Jin J;Huang Z
雷公藤内酯醇是雷公藤的主要活性成分。（TWHF）具有广泛的药理活性。然而，雷公藤甲素的毒性，特别是肝毒性，限制了其临床应用。雷公藤甲素的肝毒性尚未得到很好的表征。本研究的目的是探讨NF-E2相关因子2（Nrf2）在雷公藤甲素诱导的毒性中的作用，以及Nrf2的激活是否可以保护雷公藤甲素诱导的肝毒性。结果表明，雷公藤内酯醇可引起HepG2细胞氧化应激和细胞损伤，Nrf2基因敲减可加重这些毒性作用，而Nrf2基因过表达可抵消这些毒性作用。用典型的Nrf2激动剂萝卜硫素（SFN）治疗可减轻BALB/C小鼠中雷公藤内酯醇诱导的肝功能障碍、结构损伤、谷胱甘肽耗竭和抗氧化酶减少。此外，SFN对雷公藤甲素诱导的肝损伤的肝保护作用与Nrf2及其下游靶点的激活有关。总的来说，这些结果表明，Nrf2激活保护雷公藤甲素诱导的肝毒性。
Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF), has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2) in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN), attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.
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