Table 1.

Anti-inflammatory effects of equol.

#	Authors	Type	Findings	Has Effect
1	Blay [61]	In vitro	Equol (10 μM) significantly inhibited the overproduction of NO and PGE2 induced by LPS plus INF-γ when a pre-treatment was performed or when administered during activation. Moreover, equol regulated the gene transcription of cytokines and inflammatory markers. Genistein (20 μM) exerted similar anti-inflammatory effects, but daidzein did not.	Yes
2	Johnson [62]	In vitro	Equol exhibited protective effects against pro-inflammatory cytokines (IL-6 and TNF-α) and NO production in murine microglia cells. Equol also showed greater permeability through artificial gut and blood-brain barriers compared to daidzein.	Yes
3	Obiorah [63]	In vitro	Equol and ISFs induced endoplasmic reticulum stress and inflammatory response stress-related genes in a comparable manner to estrogens. Equol and ISFs induced proliferation of estrogenized breast cancer cells (simulating a perimenopausal state) but induced apoptosis of estrogen-deprived cells (simulating a postmenopausal state).	Yes
4	Nagarajan [64]	In vitro	In an in vitro LPS-induced inflammation model, equol dose-dependently inhibited LPS-induced MCP-1 secretion by macrophages.	Yes
5	Subedi [65]	In vitro	In microglial cells, equol inhibited TLR4 activation, MAPK activation, NF-kB-mediated transcription of inflammatory mediators, production of NO, release of PGE-2, and secretion of TNF-α and IL-6 in LPS-activated murine microglia cells.	Yes
6	Moriyama [66]	In vitro	Equol attenuated LPS-induced NO production with a concomitant decrease in the expression of iNOS. Equol did not affect the LPS-induced increase in intracellular ROS production. Increased NO production is a well-known inflammatory change in astrocytes stimulated by LPS. Attenuation of NO production by equol may mitigate LPS-induced neuroinflammation in astrocytes.	Yes
7	Lin [67]	In vivo	Equol-administered collagen-induced arthritis mice had a lower severity of arthritis symptoms. Equol administration suppressed the expression of IL-6 and its receptor in the inflamed area of collagen-induced arthritis mice.	Yes
8	Yokosuka [34]	In vivo	In ovariectomized mice induced to have intracranial aneurysms, equol protected against aneurysm formation; the disruption of the intestinal microbial conversion of daidzein to equol abolished daidzein’s protective effect against aneurysm formation. Moreover, mice treated with equol had lower inflammatory cytokines in their cerebral arteries.	Yes
9	van der Velpen [35]	Human	In the adipose tissue of postmenopausal women, the expression of inflammation-related genes was upregulated in equol producers but downregulated in non-producers.	Yes
10	Törmälä [68]	Human	ISFs caused a decrease in the VCAM-1 and platelet-selectin. The fall in platelet-selectin was more marked in equol producers. No changes appeared in SHBG, CRP, or ICAM-1.	Yes
11	Reverri [69]	Human	Consuming soy improved arterial stiffness as was assessed by the augmentation index, but did not improve the inflammatory biomarkers (CRP, TNF-α, IL-6, IL-18, and IL-10). The addition of equol-producing status as a covariate did not significantly change these results.	No
12	Nicastro [70]	Human	Equol, while not associated with a decrease in CRP level, was associated with decreased geometric mean WBC counts, comparing the highest quartile to the lowest.	Yes
13	Greany [71]	Human	An RCT of 34 postmenopausal women on 44 mg/day of ISFs showed that the ISFs did not influence the concentrations of Hcy, CRP, sE-selectin, sVCAM-1, and sICAM-1. Equol-producing status did not modify the associations.	No
14	Mangano [72]	Human	In women who received the ISFs intervention, there was no significant differences in percent change in the serum inflammatory markers between equol producers and non-producers.	No

Abbreviations: NO, nitric oxide; PGE2, prostaglandin E₂; LPS, lipopolysaccharide; INF-γ, interferon gamma; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α; MCP-1, monocyte chemoattractant protein-1; MetS, metabolic syndrome; CRP, C-reactive protein; sICAM, soluble intercellular adhesion molecule; VCAM-1, vascular cell adhesion molecule 1; SHBG, sex hormone-binding globulin; ICAM-1, intercellular adhesion molecule 1; IL-8, interleukin-8; IL-10, interleukin-10; WBC, white blood cell; Hcy, homocysteine; sE-selectin, soluble endothelial leukocyte adhesion molecule-1; TLR4, Toll-like receptor 4; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; RCT, randomized controlled trial.