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Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, AR 72079, USA
Author to whom correspondence should be addressed.
Current address: Oncology Business Unit, WuXi AppTec Co., Ltd., Shanghai 200131, China.
Academic Editor: Paul B. Tchounwou
Int. J. Environ. Res. Public Health 2016, 13(4), 373;
Received: 17 February 2016 / Revised: 20 March 2016 / Accepted: 22 March 2016 / Published: 26 March 2016
(This article belongs to the Special Issue Endocrine Disruptors and Public Health)
PDF [845 KB, uploaded 26 March 2016]


Flavonoids are frequently used as dietary supplements in the absence of research evidence regarding health benefits or toxicity. Furthermore, ingested doses could far exceed those received from diet in the course of normal living. Some flavonoids exhibit binding to estrogen receptors (ERs) with consequential vigilance by regulatory authorities at the U.S. EPA and FDA. Regulatory authorities must consider both beneficial claims and potential adverse effects, warranting the increases in research that has spanned almost two decades. Here, we report pathway enrichment of 14 targets from the Comparative Toxicogenomics Database (CTD) and the Herbal Ingredients’ Targets (HIT) database for 22 flavonoids that bind ERs. The selected flavonoids are confirmed ER binders from our earlier studies, and were here found in mainly involved in three types of biological processes, ER regulation, estrogen metabolism and synthesis, and apoptosis. Besides cancers, we conjecture that the flavonoids may affect several diseases via apoptosis pathways. Diseases such as amyotrophic lateral sclerosis, viral myocarditis and non-alcoholic fatty liver disease could be implicated. More generally, apoptosis processes may be importantly evolved biological functions of flavonoids that bind ERs and high dose ingestion of those flavonoids could adversely disrupt the cellular apoptosis process. View Full-Text
Keywords: estrogen receptor; flavonoids; target; gene; pathway analysis estrogen receptor; flavonoids; target; gene; pathway analysis

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Ye, H.; Ng, H.W.; Sakkiah, S.; Ge, W.; Perkins, R.; Tong, W.; Hong, H. Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors. Int. J. Environ. Res. Public Health 2016, 13, 373.

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