Lee Wook, Kim Seung-Jin
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Republic of Korea.
Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, Republic of Korea.
Front Mol Biosci. 2023 Feb 27;10:1147301. doi: 10.3389/fmolb.2023.1147301. eCollection 2023.
Excessive and chronic alcohol intake can lead to the progression of alcoholic liver disease (ALD), which is a major cause of morbidity and mortality worldwide. ALD encompasses a pathophysiological spectrum such as simple steatosis, alcoholic steatohepatitis (ASH), fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH2) is the most vital enzyme that produces acetate from acetaldehyde and is expressed at high levels in the liver, kidneys, muscles, and heart. The ALDH2*2 allele is found in up to 40% of East Asian populations, and has a significant impact on alcohol metabolism. Interestingly, several studies have shown that individuals with ALDH2 deficiency are more susceptible to liver inflammation after drinking alcohol. Furthermore, there is growing evidence of an association between ALDH2 deficiency and the development of cancers in the liver, stomach, colon, and lung. Isoflavone analogues are low molecular-weight compounds derived from plants, similar in structure and activity to estrogen in mammals, known as phytoestrogens. Recent studies have reported that isoflavone analogues have beneficial effects on the progression of ALD. This mini-review summarizes the current knowledge about the roles of isoflavone analogues in ALD and discusses the therapeutic potential of isoflavone analogues in liver pathophysiology. In particular, we highlight the significance of computational approaches in this field.
过量和长期饮酒会导致酒精性肝病（ALD）的进展，ALD是全球发病和死亡的主要原因。ALD包括一系列病理生理状况，如单纯性脂肪变性、酒精性脂肪性肝炎（ASH）、纤维化、酒精性肝硬化和肝细胞癌（HCC）。乙醛脱氢酶（ALDH2）是将乙醛转化为乙酸的最重要的酶，在肝脏、肾脏、肌肉和心脏中高表达。高达40%的东亚人群存在ALDH2*2等位基因，这对酒精代谢有重大影响。有趣的是，多项研究表明，ALDH2缺乏的个体饮酒后更容易发生肝脏炎症。此外，越来越多的证据表明，ALDH2缺乏与肝脏、胃、结肠和肺癌的发生有关。异黄酮类似物是源自植物的低分子量化合物，其结构和活性与哺乳动物中的雌激素相似，被称为植物雌激素。最近的研究报告称，异黄酮类似物对ALD的进展具有有益作用。这篇小型综述总结了关于异黄酮类似物在ALD中作用的当前知识，并讨论了异黄酮类似物在肝脏病理生理学中的治疗潜力。特别是，我们强调了计算方法在该领域的重要性。
