Medical Laboratory, Wuming Hospital of Guangxi Medical University, Wuming, Guangxi, PR China.
Medical Laboratory, Wuming Hospital of Guangxi Medical University, Wuming, Guangxi, PR China.
Life Sci. 2021 May 1;272:119229. doi: 10.1016/j.lfs.2021.119229. Epub 2021 Feb 16.
Formononetin is a promising bioactive phytoestrogen with evident pharmacological properties. However, the potential hepatoprotective benefit is evidenced limitedly in experiments. This study was designed to investigate the hepatoprotective mechanism and benefit of formononetin against liver injury via network pharmacology combined with biochemical determination. The computational data from network pharmacology identified the crucial genes of formononetin against liver injury, listed as TNF-α, NFκB-p65, TLR3, RELA, TRAF6, IKBKG, IKBKB, TNFRSF1A. And the anti-liver injury of formononetin were mainly involved in suppression of inflammatory pathways, including TNF signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway. In animal investigation, formononetin-dosed mice showed reduced body weight loss and hepatomegaly, meliorated liver function, suppressed hepatotoxicity and inflammatory reaction. Furthermore, the down-regulated expressions of TNF-α, NFκB-p65, TLR3 mRNAs and proteins in the livers of formononetin-dosed mice were detected accordingly. Therefore, we concluded that computational findings based on network pharmacology reveal the pharmacological targets, biological processes, and molecular mechanisms of formononetin against liver injury before some of findings were partially certified in vivo. Overall, formononetin may be a potential active component to prevent or treat liver injury.
芒柄花素是一种很有前途的具有明显药理活性的植物雌激素。然而，其对肝脏的保护作用在实验中证据有限。本研究旨在通过网络药理学结合生化测定来探讨芒柄花素防治肝损伤的作用机制和益处。网络药理学的计算数据确定了芒柄花素防治肝损伤的关键基因，包括 TNF-α、NFκB-p65、TLR3、RELA、TRAF6、IKBKG、IKBKB、TNFRSF1A。芒柄花素的抗肝损伤作用主要涉及抑制炎症途径，包括 TNF 信号通路、NF-κB 信号通路、Toll 样受体信号通路。在动物研究中，芒柄花素给药组小鼠体重下降和肝肿大减轻，肝功能改善，肝毒性和炎症反应受到抑制。此外，还检测到芒柄花素给药组小鼠肝脏中 TNF-α、NFκB-p65、TLR3mRNA 和蛋白的表达下调。因此，我们得出结论，基于网络药理学的计算结果揭示了芒柄花素防治肝损伤的药理靶点、生物学过程和分子机制，部分结果在体内得到了部分验证。总之，芒柄花素可能是预防或治疗肝损伤的一种潜在活性成分。
