β-Asarone Alleviates Post-stroke Neuroinflammation and Improves Mitochondrial Quality Via the BNIP3/BNIP3L-dependent Mitophagy Pathway.

Ischemic stroke (IS) is a leading cause of death and disability worldwide, with mitophagy playing a central role in post-stroke neurological dysfunction. β-Asarone, a major bioactive component derived from the traditional herb Acorus tatarinowii, possesses antioxidant, anti-inflammatory, and neuroprotective properties. However, whether β-asarone ameliorates IS by regulating mitophagy and its underlying mechanisms remains unclear. This study aimed to investigate whether β-asarone exerts neuroprotective effects against IS by modulating BNIP3/BNIP3L-mediated mitophagy. A middle cerebral artery occlusion (MCAO) rat model and an oxygen-glucose deprivation/reperfusion (OGD/R) cell model were established. Neuroprotective effects were evaluated using neurological behavioral scores, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, and Nissl staining. Mitochondrial function was assessed by measuring reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP). Mitophagy was observed via transmission electron microscopy (TEM) and fluorescence microscopy. Western blot (WB) analysis was performed to detect BNIP3/BNIP3L pathway proteins. Results showed that β-asarone enhanced mitophagy, improved mitochondrial function, and alleviated post-stroke neuroinflammation. Conversely, the autophagy inhibitor 3-methyladenine (3-MA) impaired mitophagic function, exacerbating ischemia-induced brain injury and inflammation, while β-asarone treatment reversed these detrimental effects. In summary, β-asarone mitigates neuroinflammation and neuronal injury after IS, at least partly through promoting BNIP3/BNIP3L-mediated mitophagy, highlighting this pathway as a promising therapeutic target for IS.