对乙酰氨基酚
化学
肝损伤
药理学
CYP2E1
氧化应激
药品
药物开发
药效学
细胞色素P450
生物化学
药代动力学
酶
医学
作者
Xiankuan Li,Jiaming Ge,Mengyuan Li,Sha Deng,Jiarong Li,Yucong Ma,Jian Zhang,Yanchao Zheng,Lin Ma
标识
DOI:10.1016/j.bioorg.2021.105476
摘要
Schisandrae Chinensis Fructus (SCF) was a Traditional Chinese Medicine for protecting liver. However, underlying therapeutic mechanisms of these bioactive lignans from SCF similar hepatoprotective effects against drug-induced liver injury (DILI) by acetaminophen (APAP) are still unclear. This study aims to discover the potential regulation mechanisms of Schisandrol A in the treatment of DILI by APAP. The integrated UPLC-Q-TOF/MS, pharmacodynamic study, histopathological combination with network pharmacology and molecular docking technology were used to explore the potential mechanisms. The results showed that Schisandrol A reduced the level of AST, ALT, MDA, PNP, TNF-α and IL-1β, increased the levels of the GSH against acute liver failure. Additionally, Schisandrol A could improve the morphological characteristics of DILI by APAP in mice with liver tissue. Molecular docking results had showed that Schisandrol A with high scores when docking with COX-2, ALOX5, CYP2E1, CYP2C9, CYP2C19, EGFR SRC, Nrf2, MAPK14 and MAPK8. The study demonstrated that Schisandrol A could play critical roles in DILI by APAP via regulating TNF signaling pathway, inhibiting oxidative stress, inflammation and inhibiting the activities of cytochrome P450 enzymes, which contributed to searching for leading compounds and the development of new drugs for DILI by APAP.
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