Gen inhibiting the Wnt/Ca²⁺ signaling pathway alleviates cerebral ischemia/reperfusion injury

Cerebral ischemia/reperfusion injury (CIRI) is a major complication of acute ischemic stroke (AIS), characterized by calcium overload, oxidative stress, and cell apoptosis. In this study, we investigated the therapeutic potential of Genistein (Gen) in alleviating CIRI by focusing on its effects on the Wnt/Ca²⁺ signaling pathway. Using a rat model of cerebral ischemia/reperfusion and in vitro experiments on PC12 cells, we observed that Gen treatment reduced infarct size, improved neurological function, and mitigated calcium overload, oxidative stress, and apoptosis. Further analysis revealed that Gen regulates key proteins in the Wnt/Ca²⁺ signaling pathway, including Wnt5a and Frizzled-2, effectively preventing intracellular calcium accumulation and subsequent damage. The knockdown of Frizzled-2 confirmed the pathway's role in mediating calcium overload and subsequent damage. Our findings suggest that Gen alleviates CIRI by inhibiting the Wnt/Ca²⁺ signaling pathway, positioning it as a promising candidate for therapeutic intervention in stroke treatment.