Table 2.
Antioxidative effects of equol.
| # | Authors | Type | Findings | Has Effect |
|---|---|---|---|---|
| 1 | Lin [93] | In vitro | Equol was shown to protect chicken intestinal epithelial cells from oxidative damage by promoting the expression of antioxidant genes, increasing the activities of antioxidant enzymes, and enhancing antioxidant capacity. Equol significantly enhanced total SOD activity and the Nrf2 transcript. | Yes |
| 2 | Pereboom [92] | In vitro | Equol decreased the intracellular production of the superoxide anion and hydrogen peroxide content of phagocytic cells. | Yes |
| 3 | Hwang [96] | In vitro | Equol and ascorbic acid interacted synergistically in preventing LDL oxidation. All phases of LDL oxidation were affected by these compounds, which is atypical of the behavior of antioxidants that are consumed during the early phases. Equol was more potent than daidzein and genistein because of its absence of a carbonyl group, C2–C3 double bond and flanking hydroxyl groups in the pyran ring. | Yes |
| 4 | Pažoureková [91] | In vitro | Upon activation by ROS, neutrophils treated by equol produced less p40 phox (a component of NADPH oxidase, responsible for the assembly of functional oxidase in intracellular membranes) both extra- and intracellularly to the control. | Yes |
| 5 | Choi [97] | In vitro | Equol pretreatment significantly decreased levels of oxidative stress biomarkers such as thiobarbituric acid-reactive substances, carbonyl content and serum 8-hydroxy-2-deoxyguanosine. Moreover, equol increased the activity of CAT, superoxide dismutase, GPx, and glutathione reductase. In addition, equol possessed anticancer activity through acting as an antioxidant and therefore reduced apoptosis. | Yes |
| 6 | Wei [98] | In vitro | Low doses of equol could prevent skeletal muscle cell damage induced by hydrogen peroxide. Equol increased cell viability, the concentration of MDA content, and LDH activity. | Yes |
| 7 | Kamiyama [99] | In vitro | Equol might contribute to a reduced level of oxLDL-stimulated apoptosis linked to the reduced generation of intracellular ROS in human umbilical vein endothelial cells. | Yes |
| 8 | Sierens [100] | In vitro | Equol was able to function as an antioxidant, scavenging potentially harmful free radicals. Equol protected against oxidative-induced DNA damage. Pretreatment of a physiological range of equol offered protection against the hydrogen peroxide-mediated DNA damage in human lymphocytes cells. This protection was greater than that offered by the addition of antioxidant vitamins ascorbic acid and alpha-tocopherol, or the compounds 17β-estradiol and tamoxifen, which have similar structures to ISFs and are known to have moderate antioxidant activity. | Yes |
| 9 | Rüfer [101] | In vitro | Equol exhibited higher antioxidant activity than daidzein and about the same antioxidant capacity as the oxidative metabolites of daidzein and genistein despite the lack of the 2,3-double bond with the 4-oxo group and a 5,7-dihydroxyl structure. The antioxidative effect was tested by an ORAC assay which determined the ability of compounds to scavenge peroxyl radicals. | Yes |
| 10 | Hwang [51] | In vitro | Equol inhibited LDL oxidation in vitro and LDL oxidative modification by monocyte/macrophages. The antioxidant effect of equol was found to be mediated by the inhibition of superoxide radical production and manifested through enhanced levels of free NO. Equol had a greater antioxidant activity than genistein and daidzein. | Yes |
| 11 | Sierens [102] | In vitro | Pretreatment with equol significantly protected sperm DNA against oxidative damage. Compared with ascorbic acid and alpha-tocopherol, being added at physiological concentrations, genistein was the most potent antioxidant, followed by equol, ascorbic acid, and alpha-tocopherol. Equol might have a role to play in antioxidant protection against male infertility. | Yes |
| 12 | Arora [103] | In vitro | Compared to genistein and daidzein with their glycosylated and methoxylated derivatives, equol and its 4-hydroxy and 5-hydroxy derivatives were more potent antioxidants, suggesting that the absence of the 2, 3-double bond and the 4-oxo group on the ISF nucleus enhanced antioxidant activity. | Yes |
| 13 | Turner [104] | In vitro | Equol inhibited the oxidation of LDL 2.65-fold more than its parent compound daidzein. | Yes |
| 14 | Choi [94] | In vitro | Equol acted as an antioxidant in the brains of rats. The ratio of GSH/GSSG in primary cortical neuron cells exposed to equol for 24 and 72 h significantly decreased in a time- and dose-dependent manner. Moreover, equol treatment significantly increased the LDH release in a time-and dose-dependent manner. | Yes |
| 15 | Gou [90] | In vitro | Equol protected chicken macrophages from oxidative stress induced by lipopolysaccharide through reducing lipid peroxidation products such as MDA and enhancing the contents of antioxidants such as glutathione and the activities of relevant antioxidase enzymes such as total SOD; effects were also seen in gene expression related to the immune response and increased contents of cytokines. | Yes |
| 16 | Liu [105] | In vitro | Equol elevated brain antioxidant activity by increasing SOD, CAT, and GPx levels. MDA levels and AChE activity were decreased in hypertensive and vascular dementia rats. Equol further improved the long- and short-term memory of the rats. | Yes |
| 17 | Vedavanam [106] | In vivo | The order of the half-maximal inhibitory concentration values, the indication of the potency of inhibiting glucose-induced LDL lipid peroxidation observed for the compounds, was equol > genistein > daidzein. | Yes |
| 18 | Choi [89] | In vivo | Equol might act as an antioxidant through an inhibition of oxidative stress and the stimulation of CAT and SOD, but could also cause pro-oxidant effects, such as the reduction of the GSH/GSSG ratio, depending on the treatment period. A study in mice showed that equol administration significantly inhibited biomarkers of oxidative stress (thiobarbituric acid-reactive substances value, carbonyl content, and serum 8-hydroxydeoxyguanosine). Moreover, the CAT and total SOD activities and their transcripts were significantly increased by equol. Although equol increased the glutathione peroxidase activity in mice treated with equol for 1-week, long-term administration of equol (7 weeks) caused a decrease in the ratio of GSH/GSSG and the activities of GPx and glutathione reductase. | Yes |
| 19 | Ma [107] | In vivo | A study in male and ovariectomized female rats with transient middle cerebral artery occlusion revealed that the pretreatment of equol significantly reduced infarct size in both sexes. This neuroprotection was accompanied by a decrease in the NADPH oxidase activity and superoxide levels in the brain. In addition, equol reduced plasma thiobarbituric acid reactive substances and neurological deficits up to 7 days after injury. | Yes |
| 20 | Horiuchi [108] | In vitro | The study demonstrated that equol had suppressive effects against oxidative stress in pancreatic β-cells in a dose-dependent manner and presumably through activating PKA signaling. | Yes |
| 21 | Jackman [33] | In vivo | Equol exerted weak antioxidant effects in cerebral arteries, whereas the effects of daidzein were insignificant. Antioxidant activity was assessed as the reduction in NADPH-induced superoxide levels. | Yes |
| 22 | Widyarini [109] | In vivo | In addition to the activation of estrogenic signaling pathways for photoprotection, equol also provided UV-protective antioxidant effects that depend partially on HO-1 induction. Equol dose-dependently inhibited the oxidative stress measured as UVA-induced lipid peroxidation on mouse skin. A component of the equol lipid protection capacity is attributed to endogenous cutaneous antioxidant enzymes, including the inducible stress protein HO-1. | Yes |
| 23 | Nhan [110] | Human | Urinary equol was not associated with the secretion of urinary F2 isoprostane, a measure of cellular lipid peroxidation, after ISF treatment in postmenopausal women. However, the observations on the effect of equol were limited because only two of the eight subjects were equol producers, one of whom experienced a large increase in the biomarker excretion, whereas the other experienced small decreases. | No |
| 24 | Hidayat [36] | Human | The level of MDA, an oxidative stress marker, was lower in equol producers than non-producers. This RCT was conducted with 190 postmenopausal women aged 47–60 who received 100 mg ISFs for 6 months. The random allocation of ISFs intervention was carried out separately by equol-producing status. | Yes |
| 25 | Richardson [95] | In vitro | Equol might have a beneficial effect in delaying the onset and decreasing the severity of symptoms in Friedreich’s ataxia patients by an antioxidant mechanism, such as reducing the ROS-induced modification of proteins and lipids and impaired mitochondrial function. These effects were independent of the ERβ. | Yes |
Abbreviations: ROS, reactive oxygen species; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; MDA, malondialdehyde; AChE, acetylcholinesterase; PKA, protein kinase A; Nrf2, nuclear factor erythroid 2–related factor 2; NADPH, nicotinamide adenine dinucleotide phosphate; LDH, L-lactate dehydrogenase; ORAC, oxygen radical absorbance capacity; GSH/GSSG, reduced/oxidized glutathione; DNA, deoxyribonucleic acid; HO-1, heme oxygenase-1; NQO1, NADPH-quinone oxidoreductase 1; UV, ultraviolet.