Deptartment of Life Science, Faculty of Life Science, Kyushu Sangyo University, Higashi-ku, Fukuoka, Japan.
J Nutr Biochem. 2023 Apr;114:109250. doi: 10.1016/j.jnutbio.2022.109250. Epub 2022 Dec 10.
Flavonoids are a major group of phytoestrogens associated with physiological effects, and ecological and social impacts. Although the estrogenic activity of flavonoids was reported by researchers in the fields of medical, environmental and food studies, their molecular mechanisms of action have not been comprehensively reviewed. The estrogenic activity of the respective classes of flavonoids, anthocyanidins/anthocyanins, 2-arylbenzofurans/3-arylcoumarins/α-methyldeoxybenzoins, aurones/chalcones/dihydrochalcones, coumaronochromones, coumestans, flavans/flavan-3-ols/flavan-4-ols, flavanones/dihydroflavonols, flavones/flavonols, homoisoflavonoids, isoflavans, isoflavanones, isoflavenes, isoflavones, neoflavonoids, oligoflavonoids, pterocarpans/pterocarpenes, and rotenone/rotenoids, was summarized through a comprehensive literature search, and their structure-activity relationship, biological activities, signaling pathways, and applications were discussed. Although the respective classes of flavonoids contained at least one chemical mimicking estrogen, the mechanisms varied, such as those with estrogenic, anti-estrogenic, non-estrogenic, and biphasic activities, and additional activities through crosstalk/bypassing, which exert biological activities through cell signaling pathways. Such mechanistic variations of estrogen action are not limited to flavonoids and are observed among other broad categories of chemicals, thus this group of chemicals can be termed as the "estrogenome". This review article focuses on the connection of estrogen action mainly between the outer and the inner environments, which represent variations of chemicals and biological activities/signaling pathways, respectively, and form the basis to understand their applications. The applications of chemicals will markedly progress due to emerging technologies, such as artificial intelligence for precision medicine, which is also true of the study of the estrogenome including estrogenic flavonoids.
类黄酮是与生理效应、生态和社会影响相关的植物雌激素的主要类别。尽管医学、环境和食品研究领域的研究人员已经报道了类黄酮的雌激素活性，但它们的作用机制尚未得到全面综述。类黄酮各自类别，如花青素/花色苷、2-芳基苯并呋喃/3-芳基香豆素/α-甲基去氧苯并呋喃、橙酮/查尔酮/二氢查尔酮、香豆素色酮、大豆素、黄烷醇/黄烷-3-醇/黄烷-4-醇、黄烷酮/二氢黄酮醇、黄酮醇、异黄酮、异黄烷、异黄酮、异黄酮、新黄烷、低聚黄酮、紫檀烷/紫檀烷、鱼藤酮/鱼藤酮类，通过全面的文献检索，总结了它们的结构-活性关系、生物活性、信号通路和应用。虽然类黄酮各自类别中至少包含一种化学模拟雌激素的物质，但机制却各不相同，如具有雌激素、抗雌激素、非雌激素和双相活性，以及通过串扰/旁路的额外活性，通过细胞信号通路发挥生物活性。这种雌激素作用的机制变化不仅限于类黄酮，也存在于其他广泛类别的化学物质中，因此，这组化学物质可以被称为“雌激素组”。本文综述主要关注雌激素作用的连接主要在外部和内部环境之间，分别代表化学物质和生物活性/信号通路的变化，并构成理解它们应用的基础。由于人工智能等新兴技术在精准医学中的应用，化学物质的应用将显著进步，包括雌激素类黄酮在内的雌激素组的研究也是如此。
