Kaempferol Plays a Neuroprotection Role by Alleviating Oxidative Stress via AKT/Nrf2/HO-1 Pathway and Inhibiting Apoptosis in Intracerebral Hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a common yet severe cerebrovascular disorder associated with high morbidity, disability, and mortality rates. Kaempferol (Kae), a natural flavonoid with potent antioxidant and anti-inflammatory properties, has shown promise in neuroprotection; however, its therapeutic potential in promoting neurological recovery after ICH remains unclear. In this study, we investigated the neuroprotective effects of Kae in ICH and explored its underlying mechanisms using in vitro and in vivo models. For in vitro experiments, primary hippocampal neurons were pretreated with Kae for 2 h before hemin exposure (24 h). In vivo, rats received intraperitoneal Kae injections for 5 days pre-operation and 3 days post-operation. Using a combination of techniques—including SOD (Superoxide dismutase), MDA (malondialdehyde), and GSH (glutathione) assays, mitochondrial membrane potential evaluation, flow cytometry, immunofluorescence, FJC staining, and TUNEL staining—we demonstrated that Kae exerts neuroprotective, antioxidant, and anti-apoptotic effects. Western blot analysis revealed that Kae mitigates oxidative stress (OS) by modulating the AKT/Nrf-2/HO-1 signaling pathway. Further mechanistic studies confirmed that Kae enhances this pathway, thereby reducing oxidative damage in both in vitro and in vivo settings. Additionally, Kae upregulated Bcl-2 expression while downregulating BAX and cleaved Caspase-3, highlighting its anti-apoptotic role. Our findings suggest that Kae protects against ICH-induced brain injury, potentially through the suppression of oxidative stress and apoptosis. This study provides novel insights into the therapeutic potential of Kae in ICH treatment.