School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China.
College of Animal Science, Zhejiang University, Hangzhou 310058, Zhejiang, P. R. China.
J Agric Food Chem. 2023 Feb 1;71(4):1930-1943. doi: 10.1021/acs.jafc.2c05747. Epub 2023 Jan 18.
Alcohol-related liver disease (ALD) is one of the most prevalent forms of liver disease in the world. Acetaldehyde, an intermediate product of alcohol catabolism, is a cause of liver injury caused by alcohol. This study was designed to evaluate the protective role and mechanism(s) of genistein against acetaldehyde-induced liver injury in the pathological process of ALD. We found that genistein administration significantly ameliorated alcohol-induced hepatic steatosis, injury, and inflammation in mice. Genistein supplementation markedly reversed hepatic oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and hepatocellular apoptosis in both alcohol-fed mice liver and acetaldehyde-treated hepatocytes. The mechanistic experiments revealed that the restoration of genistein administration rescued heme oxygenase-1 (HO-1) reduction at both transcriptional and protein levels in either alcohol-fed mice liver or acetaldehyde-treated hepatocytes, and the beneficial aspects derived from genistein were abolished in antioxidase heme oxygenase-1 (HO-1)-deficient hepatocytes. Moreover, we confirmed that genistein administration-restored hepatic nuclear factor erythroid 2-related factor 2 (NRF2), a key transcriptional regulator of HO-1, was involved in the protective role of genistein in ALD. This study demonstrated that genistein ameliorated acetaldehyde-induced oxidative stress and liver injury by restoring the hepatic NRF2-HO-1 signaling pathway in response to chronic alcohol consumption. Therefore, genistein may serve as a potential therapeutic choice for the treatment of ALD.
酒精相关性肝病 (ALD) 是世界上最常见的肝病形式之一。乙醛是酒精代谢的中间产物，是酒精引起肝损伤的原因。本研究旨在评估染料木黄酮对 ALD 病理过程中乙醛诱导的肝损伤的保护作用及其机制。我们发现，染料木黄酮给药可显著改善酒精诱导的小鼠肝脂肪变性、损伤和炎症。染料木黄酮补充剂可显著逆转酒精喂养小鼠肝脏和乙醛处理的肝细胞中的肝氧化应激、内质网应激、线粒体功能障碍和肝细胞凋亡。机制实验表明，染料木黄酮给药可恢复酒精喂养小鼠肝脏或乙醛处理的肝细胞中 HO-1 的转录和蛋白水平降低，而抗氧化酶血红素加氧酶-1 (HO-1) 缺陷型肝细胞中源自染料木黄酮的有益方面被消除。此外，我们证实，染料木黄酮给药恢复了肝核因子红细胞 2 相关因子 2 (NRF2)，即 HO-1 的关键转录调节因子，参与了染料木黄酮在 ALD 中的保护作用。这项研究表明，染料木黄酮通过恢复肝脏 NRF2-HO-1 信号通路来改善乙醛诱导的氧化应激和肝损伤，从而对慢性酒精摄入产生反应。因此，染料木黄酮可能成为治疗 ALD 的潜在治疗选择。
