Gao Ya, Xi Boting, Li Jiani, Li Zimeng, Xu Jie, Zhong Mingli, Xu Qiongmei, Lian Yuanyu, Wei Riming, Wang Liping, Cao Houkang, Jin Ling, Zhang Kefeng, Dong Jianghui
College of Pharmacy, Guilin Medical University, Guilin, Guangxi, China.
College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.
J Cell Physiol. 2020 Oct 8. doi: 10.1002/jcp.30083.
The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB; TLR-4/NF-κB) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-κB inhibitor-α, NF-κB inhibitor-β, and NF-κB inhibitor-ε activation, while inhibiting NF-κB inhibitor-ζ. Subsequently, the decrease of phosphorylation of nuclear factor-κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR-4/NF-κB signals.
本研究旨在探讨滨蒿内酯（SCO）在肝纤维化中的作用。为此，我们进行了体内和体外实验。在体内实验中，将大鼠分为六组，即对照组、四氯化碳组、秋水仙碱组以及SCO组，其中SCO组又分为SCO50、SCO100和SCO200组，分别给予50、100和200mg/kg的SCO剂量进行处理。此外，研究表明SCO通过抑制Toll样受体4（TLR-4）来抑制Toll样受体4/核因子κB（NF-κB；TLR-4/NF-κB）信号，进而下调髓样分化因子88（MyD88）的表达，促进NF-κB抑制因子α、NF-κB抑制因子β和NF-κB抑制因子ε的激活，同时抑制NF-κB抑制因子ζ。随后，核因子κB水平磷酸化的降低导致下游炎性因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β的下调，从而减轻肝纤维化。值得注意的是，SCO200处理组的改善最为显著。因此，我们得出结论，SCO通过抑制TLR-4/NF-κB信号减轻肝纤维化。
