Isoflavones from Semen Sojae Preparatum Improve Atherosclerosis and Oxidative Stress by Modulating Nrf2 Signaling Pathway through Estrogen-Like Effects

Atherosclerosis (AS) often occurs in cardiovascular disease, which is a chronic vascular disease and is harmful to human health. Oxidative stress is involved in its etiology. This study aimed to determine the effectiveness of Isoflavones from semen sojae preparatum (ISSP) in inhibiting oxidative stress and its important molecular mechanisms through in vivo and in vitro experiments. ApoE(−/−) mice were used to establish atherosclerosis models through a high-fat diet, and endothelial cells were used to establish oxidative stress injury models through ox-LDL induction. The degree of oxidative stress damage was assessed by detecting changes in ET-1, LDH, SOD, and MDA indicators. It was observed that after ISSP treatment, the oxidative stress damage of mice and endothelial cells was improved. The Nrf2/AER signaling pathway is an important antioxidant pathway that has attracted our attention. Western blotting and qRT-PCR were used to detect the expression of Nrf2, HO-1, and NQO1 in mice aortae and endothelial cells. The results showed that the Nrf2 signaling pathway was activated after ISSP intervention. In addition, in this study, after preantagonizing the estrogen receptors GPR30 and ERβ, it was observed that the effects of ISSP in treating endothelial cell oxidative damage and activating the Nrf2 signaling pathway were weakened. After silencing Nrf2 by Nrf2-siRNA transfection, the effect of ISSP in treating endothelial cell oxidative damage was inhibited. This study shows that ISSP may reduce oxidative stress damage and atherosclerosis through the Nrf2 signaling pathway, and this effect may involve the GPR30 and ERβ estrogen receptors.