Table 3.
Endothelial function improvement effects of equol.
| # | Authors | Type | Findings | Has Effect |
|---|---|---|---|---|
| 1 | Joy [117] | In vitro | Nutritionally relevant plasma concentrations of equol rapidly stimulated phosphorylation of ERK1/2 and PI3K/Akt, leading to the activation of NOS and increased NO production at resting cytosolic Ca2+ levels. | Yes |
| 2 | Rowlands [119] | In vitro | Equol-stimulated mitochondrial ROS modulated endothelial redox signaling and NO release through transactivation of epidermal growth factor receptor kinase and reorganization of the F-actin cytoskeleton. | Yes |
| 3 | Cheng [115] | In vitro | Equol prevented oxidative damage to vascular function in pulmonary cells via downregulating eNOS and oxidative stress. | Yes |
| 4 | Zhang [114] | In vitro | In HUVEC, equol increased Nrf2 mRNA as well as the mRNA of the gene products of HO-1 and NQO1. Pretreatment of cells with specific endoplasmic reticulum inhibitors or PI3K/Akt increased Nrf2, HO-1, and NQO1 protein. | Yes |
| 5 | Chung [121] | In vitro | Equol had a significant antioxidant effect on the bAECs that were exposed to hydrogen peroxide. Equol pretreatment effectively inhibited the hydrogen peroxide-induced cell death by the reduction in intracellular ROS production, probably through increasing phospho-p38 MAPK. | Yes |
| 6 | Zhang [123] | In vitro | The improvement of atherosclerosis by equol through attenuation of endoplasmic reticulum stress is mediated by activating the Nrf2 signaling pathway. Equol treatment inhibited cell apoptosis and attenuated upregulation of endoplasmic reticulum stress markers in HUVECs. In an oxidative stress environment, equol treatment dose-dependently activated the Nrf2 signaling pathway. | Yes |
| 7 | Somjen [122] | In vitro | Equol, but not daidzein and genistein, had a monophasic stimulatory effect on thymidine incorporation, which boosts DNA synthesis. In human endothelial cells, equol, daidzein, and genistein stimulated DNA synthesis in a dose-dependent manner. The administration of equol, daidzein, and genistein to immature and ovariectomized female rats resulted in increased creatine phosphokinase in the aorta and in the left ventricle of the heart. | Yes |
| 8 | Kim [124] | In vitro | Equol had a vasodilatory effect on human uterine arteries vascular smooth muscle, which was mediated through antagonistic action for a receptor-dependent Ca2+ channel. | Yes |
| 9 | Johnson [62] | In vitro | Equol exhibited protective effects against NO production in murine microglial cells. Equol also showed greater permeability through artificial gut and blood-brain barriers compared to daidzein. | Yes |
| 10 | Chin-Dusting [125] | In vivo | Equol had a dose-dependent inhibition of the contractile responses to noradrenaline in rat isolated aortic rings. Equol independently increased the release of a vasoconstrictor prostanoid, such as thromboxane. | Yes |
| 11 | Jackman [33] | In vivo | In normotensive rats, equol displayed vasorelaxant activity similar to daidzein. The relaxant effect of equol was independent of intact endothelium, NOS activity, K+ channels, and gender. In the basilar artery, where superoxide levels are higher, equol exerted weak antioxidant effects, whereas the effects of daidzein were insignificant. During hypertension, equol-induced vasorelaxation was preserved, whereas relaxant responses to daidzein were impaired. | Yes |
| 12 | Matsumoto [126] | In vivo | Contractions induced by a selective 5-HT receptor agonist increased with insulin treatment, but less so with equol + insulin. In the endothelium-denuded preparations, 5-HT-induced contractions were augmented with insulin treatment but less so by equol + insulin treatment. These differences in 5-HT-induced contractions were eliminated by a large-conductance of Ca2+-activated K+ channel inhibitor. | Yes |
| 13 | Yu [116] | In vivo | Equol significantly increased regional cerebral blood flow in rats and produced an endothelium-independent relaxation in rat cerebral basilar arteries. Selective Ca2+-activated K+ channel blockers significantly inhibited equol-induced vasodilation in cerebral arteries. | Yes |
| 14 | Ohkura [120] | In vivo | Ovariectomized rats were assigned to (1) an ISF-deficient but equol-sufficient group, (2) an ISFs-deficient and equol-deficient group. In the thoracic artery, endothelium-dependent relaxation, cyclic guanosine monophosphate levels in the tissue, and eNOS synthase expression and phosphorylation were significantly higher in the first group compared to the second group. | Yes |
| 15 | Törmälä [73] | Human | Before ISF intervention, women with a 4-fold elevation in equol levels had a lower endothelial function index compared to women without this capacity. Soy supplementation had no effect on arterial stiffness or endothelial function in either group. | Yes |
| 16 | Kreijkamp-Kaspers [37] | Human | This RCT did not support the hypothesis that ISFs have beneficial effects on endothelial function in older postmenopausal women. However, in the soy-only group, systolic and diastolic blood pressure decreased, and endothelial function improved in the equol producers, whereas blood pressure increased, and endothelial function deteriorated in the non-producers. | Yes |
| 17 | Hidayat [36] | Human | ISFs did not improve endothelial functions in both the equol producers and the non-producers. The VCAM-1 and NO did not differ by equol-producing status. | No |
| 18 | Clerici [127] | Human | After ISFs treatment, the brachial artery flow-mediated vasodilatation was improved more obviously in the equol producers. | Yes |
Abbreviations: ERK1/2, extracellular signal-regulated protein kinases 1 and 2; PI3K/Akt, protein kinase 1/2 and phosphatidylinositol 3-kinase/protein kinase B; NOS, nitric oxide synthase; NO, nitric oxide; ROS, reactive oxygen species; HUVEC, human umbilical vein endothelial cell; eNOS, endothelial nitric oxide synthase; HO-1, heme oxygenase-1; NQO1, NADPH-quinone oxidoreductase 1; Nrf2, nuclear factor-erythroid 2-related factor 2; bAECs, bovine aortic endothelial cell; MAPK, mitogen-activated protein kinase; HUVECs, human umbilical vein endothelial cells; cfPWV, carotid-femoral pulse wave velocity; VCAM-1, vascular cell adhesion molecule-1; 5-HT, 5-hydroxytryptamine; Ca, calcium; K, potassium.