Scoparone alleviates hepatic fibrosis by inhibiting the TLR-4/NF-κB pathway

Scoparone alleviates hepatic fibrosis by inhibiting the TLR-4/NF-κB pathway
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Scoparone 通过抑制 TLR-4/NF-kappa B 通路减轻肝纤维化

DOI:
10.1002/jcp.30083
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发表时间:
2020-10-08
影响因子:
5.6
通讯作者:
Dong, Jianghui
Dong, Jianghui
中科院分区:
生物学2区
文献类型:
--
作者:
Gao, Ya;Xi, Boting;Dong, Jianghui

文献摘要

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本研究的目的是探讨天scoparone (SCO)在肝纤维化中的作用。为此,我们进行了体内和体外实验。将体内大鼠分为对照组、四氯化碳组和秋水仙碱组,以及SCO组、SCO50组、SCO100组和SCO200组,分别给予50、100和200 mg/kg SCO剂量。此外,SCO通过抑制TLR-4抑制toll样受体-4 (TLR-4)/核因子κ B (nf - κ B; TLR-4/ nf - κ B)信号,进而下调MyD88的表达,促进nf - κ B抑制剂- α、nf - κ B抑制剂- β和nf - κ B抑制剂-epsilon的激活,同时抑制nf - κ B抑制剂-zeta。随后,核因子-kappa B磷酸化水平降低,导致下游炎症因子肿瘤坏死因子- α (tnf - α)、白细胞介素-6 (IL-6)、IL-1 β下调,从而减弱肝纤维化。值得注意的是,SCO200治疗组表现出最显著的改善。因此,我们得出结论,SCO通过抑制TLR-4/NF-kappa B信号来减轻肝纤维化。
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-kappa B; TLR-4/NF-kappa B) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-kappa B inhibitor-alpha, NF-kappa B inhibitor-beta, and NF-kappa B inhibitor-epsilon activation, while inhibiting NF-kappa B inhibitor-zeta. Subsequently, the decrease of phosphorylation of nuclear factor-kappa B levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-alpha), 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-kappa B signals.