Objective To study the protective effect and potential mechanism of soybean isoflavones (SI) on ischemic stroke. Methods SI were isolated from soybeans and components were analyzed. An oxygen glucose deprivation/reperfusion (OGD/R)-induced PC12 cells model was constructed to investigate the effect of SI on cell survival, migration ability, apoptosis, intracellular Ca²⁺, reactive oxygen species (ROS), lactate dehydrogenase (LDH), cysteine aspartate protease-3 (Caspase-3) levels, and expressions of Kelch-like ECH associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway related proteins. A rat model of global cerebral ischemia-reperfusion injury was established using bilateral common carotid artery ligation. The effect of SI on neurological function score, brain tissue water content, proportion of cerebral infarction volume, pathological changes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), LDH activities, malondialdehyde (MDA) level, and expressions of Keap1/Nrf2 pathway related proteins in brain tissue were investigated. Results In vitro experiments showed that compared with model group, SI significantly increased cell survival rate and migration rate (P < 0.05, 0.01), decreased cell apoptosis rate and intracellular Ca²⁺, ROS, LDH, Caspase-3 levels (P < 0.05, 0.01), upregulated Nrf2, heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1) protein expressions (P < 0.01), and downregulated Keap1 protein expression (P < 0.05, 0.01). In vivo experiments, compared with model group, SI significantly improved neurological deficits, reduced brain edema and infarct volume in rats (P < 0.01), repaired brain tissue pathological damage, reduced MDA level and LDH activity in brain tissue (P < 0.01), increased SOD, CAT and GSH-Px activities in brain tissue (P < 0.01), upregulated Nrf2, HO-1 and NQO1 protein expressions in brain tissue (P < 0.01), and downregulated Keap1 protein expression in brain tissue (P < 0.01). Conclusion SI have a significant neuroprotective effect on ischemic stroke, which may be related to the activation of Keap1/Nrf2 pathway, enhancing the antioxidant capacity of body, inhibiting oxidative stress damage, reducing neuronal apoptosis and alleviating brain tissue damage.

ischemic stroke  /  soybean isoflavones  /  Keap1/Nrf2 pathway  /  oxidative stress  /  apoptosis  /  daidzin  /  glycitin  /  genistin  /  acetyl daidzin  /  acetyl glycoside  /  malonyl genistin  /  acetyl genisti