Glycycoumarin protects mice against acetaminophen-induced liver injury predominantly via activating sustained autophagy

British Journal of Pharmacology
Mingzhu YanHongbo Hu

Abstract

Acetaminophen-induced acute liver injury (AILI) is the most frequent cause of acute liver failure in developed countries. Given the significant limitations associated with N-acetyl cysteine, the only antidote used to treat AILI, the development of novel therapeutic approaches that can offer a wide range of therapeutic time-windows is clearly needed. Glycycoumarin (GCM), a natural coumarin purified from liquorice, has been previously demonstrated to possess potent hepatoprotective effects. In the present study, we aimed to investigate the therapeutic potential of GCM against AILI. Acetaminophen (300 mg·kg-1 ) was administered to male C57BL/6 mice, with and without GCM. Serum transaminases, haematoxylin and eosin staining and Western blot were used to assess hepatic damage. GCM (50 mg·kg-1 ) was highly effective against acetaminophen-induced hepatotoxicity. Moreover, GCM was superior to N-acetyl cysteine, in terms of the dosage and the therapeutic time-windows. Further mechanistic investigations revealed that the therapeutic action of GCM was not a result of inhibition of acetaminophen metabolic activation or associated with Nrf2. Instead, the protective effect of GCM appeared to be predominantly dependent on sustained activation...Continue Reading

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Citations

Dec 17, 2019·Phytotherapy Research : PTR·Enxiang ZhangHongbo Hu
Jan 12, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hartmut JaeschkeAnup Ramachandran
May 27, 2020·Oxidative Medicine and Cellular Longevity·Zhao GaoYong Gao
Jun 13, 2020·Archives of Toxicology·Qiuhua TanZhengquan Su
May 8, 2020·Oxidative Medicine and Cellular Longevity·Emad H M HassaneinAyman M Mahmoud
Mar 19, 2020·Frontiers in Pharmacology·Jiaqi ZhangYuanye Jiang
May 20, 2020·Frontiers in Pharmacology·Licong ZhaoYuanye Jiang
May 26, 2020·Biochemical and Biophysical Research Communications·Enxiang ZhangHongbo Hu

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