Table 2.

Estrogenic effects of dietary phytoestrogens.

Phytoestrogens		Relative Binding Affinity to ERs	Estrogenic Effects	References
Isoflavones	Daidzein	-Preferential affinity to ERβ in comparison with ERα (RBA 0.5 v 0.1); -Lowest binding affinity of all isoflavones.	-Inhibits ovarian cancer cells’ proliferation, migration, and induces cell-cycle arrest as selective ERβ agonist; -Chemoprevention in endometrial cancer.	[6,7]
	Genistein	-Higher affinity to ERβ in comparison with ERα (RBA 31–87 v 1–4).	-Regulated expression of target endogenous genes (CYP17, PR, ER-α, and ER-β). -Modulates ER levels in the liver, testis and lung; -Inhibits aromatase expression in breast cancer tissue; -Enhances osteoblastic differentiation and maturation by activation of ER; -Effects on reproductive and nonreproductive organs of mice models; -Preventive effect on breast and prostate cancers; -Decreases ovarian cancer risk;	[6,7,70]
	S-equol	-Preferentially binding to ERβ (RBA 10× higher for ERβ than ERα); -Higher binding affinity than its precursor daidzein.	-Binds dihydrotestosterone and inhibits in vivo prostate cancer growth; -Potent agent for menopause-related symptom relief.	[19,160]
Comestans	Coumestrol	-High binding capacity, similar to estradiol (RBA for ERβ: 77–140 and for ERα: 12–20).	-Inhibits aromatase and 3α-hydroxysteroid dehydrogenase activities; -Anticancer for ovarian, breast, lung, cervical and prostate, cancers through ER signaling pathways; -decreased endometrial cancer risk;	[161,162]
	Wedelolactone	-Acts as an agonist to both ERs.	-Activates expression of ER-regulated genes in ER-positive breast cancer cells; -Stimulates transactivation by AP-1 on ER signaling pathway.	[163]
Prenylflavonoids	6-PN	-Very weak binding capacity to ERα and ERβ (less than 1/100 of 8PN RBA to ERβ; -Weak aromatase inhibitor;	-Alters ERα-AhR crosstalk under estrogenic conditions; -Preferentially induce non-genotoxic estrogen metabolism	[164,165]
	8-PN	-Binds tighter to ERα compared to ERβ; -Acting as a pure estrogen with activity similar to estrone; -Potent aromatase inhibitor;	-Reduces the raised skin temperatures in a menopausal rat model; -Reduces hot flashes in postmenopausal women; -Increases uterine weight and height of luminal epithelial cells; -Weak osteoprotective effects;	[164,165]
	Glabridin	-Binds to ERβ with the same affinity as genistein; -Weak binding affinity to ERα.	-Induced dose-dependent increase in estrogenic activity and cell proliferation in Ishikawa cells; -Exerts estrogenic activity via the ER-α-SRC-1-co-activator complex; -Acts through the ER to induce beneficial effects of estrogen in bone and cardiovascular tissues.	[166,167]
Lignans	Arctigenin	-Moderate binding capacity for ERβ; -Weak binding affinity to ERα.	-Inhibits the activation of mTORC1 pathway by targeting ERβ; -Promotes ERβ activation in T lymphocytes	[168,169]
	Enterolactone	-Weak binding affinity to ERα and ERβ;	-Induces ERα/β transcriptional activation; -Activates estrogen-responsive genes, through direct binding to the ligand-binding domains of ERα; -Increases the expression of endogenous estrogen-responsive genes in mouse uterus. -Reduces the risk of hormone-dependent breast, uterus and prostate cancers.	[170,171]
Stilbenes	Resveratrol	-Binds with similar affinity to ER-α and ER-β; -Weak estrogenic binding ability in comparison with estradiol (~7000 times less powerful).	-Inhibits endometrial aromatase and COX-2 expression; -Suppresses vascular smooth muscle proliferation and promotes re-endothelialization after aorta injury; -Mediates its neuroprotective effects via ER activation; -Interferes with intestinal and hepatic metabolism of estrogens	[121,123]
	Pterostilbenes	-Binds with approximatively similar affinity to ER-α and ER-β.	-Inhibits colon cancer tumors growth in mice models through an ER-β-mediated mechanism; -Induces apoptosis in breast cancer cells and necrosis in xenograft tumors by targeting ER-α36; -Enhances the sex hormone secretion, further improving follicle development.	[172,173]
RBA, Relative Binding Affinity.