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

Hao Ye, Hui Wen Ng, Sugunadevi Sakkiah, Weigong Ge, Roger Perkins, Weida Tong and Huixiao Hong
Additional contact information
Hao Ye: Current address: Oncology Business Unit, WuXi AppTec Co., Ltd., Shanghai 200131, China.
Hui Wen Ng: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, AR 72079, USA
Sugunadevi Sakkiah: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, AR 72079, USA
Weigong Ge: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, AR 72079, USA
Roger Perkins: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, AR 72079, USA
Weida Tong: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, AR 72079, USA
Huixiao Hong: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, AR 72079, USA

IJERPH, 2016, vol. 13, issue 4, 1-17

Abstract: 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.

Keywords: estrogen receptor; flavonoids; target; gene; pathway analysis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2016
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