School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China.
Int Immunopharmacol. 2023 Dec;125(Pt B):111206. doi: 10.1016/j.intimp.2023.111206. Epub 2023 Nov 11.
Liver fibrosis is a major global health issue, and immune dysregulation is a main contributor. Triptolide is a natural immunosuppressive agent with demonstrated effectiveness in ameliorating liver fibrosis, but whether it exerts anti-liver fibrotic effects via immunoregulation remains obscure. In this study, first, by employing a CCL-induced liver fibrosis mouse model, we demonstrated that triptolide could alleviate pathological damage to liver tissue and attenuate liver function damaged by CCL. In addition, triptolide inhibited the expression of liver fibrotic markers such as hydroxyproline, collagen type IV, hyaluronidase, laminin, and procollagen type III, and the protein expression of α-SMA in CCL-induced liver fibrosis. Second, with the help of network pharmacology, we predicted that triptolide's anti-liver fibrotic effects might occur through the regulation of Th17, Th1, and Th2 cell differentiation, which indicated that triptolide might mitigate liver fibrosis via immunoregulation. Finally, multiplex immunoassays and flow cytometry were adopted to verify this prediction. The results suggested that triptolide could reverse the aberrant expression of inflammatory cytokines caused by CCL and regulate the differentiation of Th1, Th2, Th17, and Treg cells. In conclusion, triptolide could attenuate CCL-induced liver fibrosis by regulating the differentiation of CD T cells. The results obtained in this study extended the application of triptolide and introduced a new mechanism of triptolide's anti-liver fibrotic effects.
肝纤维化是一个全球性的健康问题，免疫失调是主要原因之一。雷公藤红素是一种天然免疫抑制剂，已被证明能有效改善肝纤维化，但它是否通过免疫调节发挥抗肝纤维化作用尚不清楚。在这项研究中，首先，我们通过 CCL 诱导的肝纤维化小鼠模型证明，雷公藤红素可以减轻肝组织的病理损伤，减轻 CCL 引起的肝功能损伤。此外，雷公藤红素抑制了羟脯氨酸、IV 型胶原、透明质酸酶、层粘连蛋白和 III 型前胶原等肝纤维化标志物以及 CCL 诱导的肝纤维化中α-SMA 的蛋白表达。其次，借助网络药理学，我们预测雷公藤红素的抗肝纤维化作用可能通过调节 Th17、Th1 和 Th2 细胞分化来实现，这表明雷公藤红素可能通过免疫调节减轻肝纤维化。最后，采用多重免疫分析和流式细胞术验证了这一预测。结果表明，雷公藤红素可以逆转 CCL 引起的炎症细胞因子的异常表达，并调节 Th1、Th2、Th17 和 Treg 细胞的分化。总之，雷公藤红素通过调节 CD T 细胞的分化可以减轻 CCL 诱导的肝纤维化。本研究的结果扩展了雷公藤红素的应用，并介绍了雷公藤红素抗肝纤维化作用的新机制。
