Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, School of Pharmacy, 12485Anhui Medical University, Hefei, China.
The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, 12485Anhui Medical University, Hefei, China.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S775-S787. doi: 10.1177/09603271211056330. Epub 2021 Nov 11.
Triptolide (TP), the main active compound extracted from medicine- (TWHF). It has anti-tumor and immunomodulatory properties. Our study aimed to investigate the mechanisms of hepatotoxicity treated with TP as well as their relationship with the NF-κB (p65) signal pathway; and to assess TP-induced hepatotoxicity after CYP2E1 modulation by the known inhibitor, clomethiazole, and the known inducer, pyrazole. Mice were given TP to cause liver injury and IHHA-1 cells were given TP to cause hepatocyte injury. The enzyme activity and hepatotoxicity changed dramatically when the CYP2E1 inhibitor and inducer were added. In comparison to the control group, the enzyme inducer increased the activity of CYP2E1, whereas the enzyme inhibitor had the opposite effect. Our findings suggest that TP is an inducer of CYP2E1 via a time-dependent activation mechanism. In addition, TP can promote oxidative stress, inflammatory and involving the NF-κB (p65) signal pathway. Therefore, we used triptolide to stimulate C57 mice and IHHA-1 cells to determine whether TP can promote oxidative stress and inflammation by activating CYP2E1 in response to exacerbated liver damage and participate in NF-κB (p65) signaling pathway.
雷公藤红素（TP），是从中药（TWHF）中提取的主要活性化合物。它具有抗肿瘤和免疫调节作用。本研究旨在探讨 TP 治疗肝毒性的机制及其与 NF-κB（p65）信号通路的关系；并评估已知抑制剂氯噻唑和已知诱导剂吡唑对 CYP2E1 调节后 TP 诱导的肝毒性。用 TP 诱导小鼠肝损伤，用 TP 诱导 IHHA-1 细胞肝损伤。当添加 CYP2E1 抑制剂和诱导剂时，酶活性和肝毒性发生了显著变化。与对照组相比，酶诱导剂增加了 CYP2E1 的活性，而酶抑制剂则产生相反的效果。我们的研究结果表明，TP 通过时间依赖性激活机制诱导 CYP2E1。此外，TP 可以促进氧化应激、炎症和涉及 NF-κB（p65）信号通路。因此，我们使用雷公藤红素刺激 C57 小鼠和 IHHA-1 细胞，以确定 TP 是否可以通过激活 CYP2E1 来促进氧化应激和炎症，从而加剧肝损伤并参与 NF-κB（p65）信号通路。
