The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury

Zhao Gao, Jiecheng Zhang, Li Wei, Xingping Yang, Yuan Zhang, Bo Cheng, Zehong Yang, Weihang Gao, Chunhui Song, Wei Miao, Kevin Williams, Changhui Liu, Qin Xu, Yongsheng Chang, Yong Gao

Research output: Contribution to journalArticle

Abstract

Acetaminophen (APAP) toxicity leads to severe acute liver injury (ALI) by inducing excessive oxidative stress, inflammatory response, and hepatocyte apoptosis. Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose.

Original languageEnglish (US)
Article number8026838
JournalOxidative Medicine and Cellular Longevity
Volume2020
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

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  • Cite this

    Gao, Z., Zhang, J., Wei, L., Yang, X., Zhang, Y., Cheng, B., Yang, Z., Gao, W., Song, C., Miao, W., Williams, K., Liu, C., Xu, Q., Chang, Y., & Gao, Y. (2020). The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury. Oxidative Medicine and Cellular Longevity, 2020, [8026838]. https://doi.org/10.1155/2020/8026838