Beta-asarone alleviated cerebral ischemia/reperfusion injury by targeting PINK1/Parkin-dependent mitophagy

Cerebral ischemia-reperfusion injury (CIRI) describes a secondary type of brain damage that happens when blood flow is restored to brain tissue; it ranks among the primary contributors of disability and mortality. The activation of PINK1/Parkin-mediated Mitophagy exerts neuroprotective effects during CIRI. Beta-asarone (β-ASA), the principal active component of traditional natural drugs such as Acori tatarinowii rhizoma and Ligusticum chuanxiong Hort, possesses anti-inflammatory, antioxidant, and autophagy-enhancing properties. However, whether β-ASA can ameliorate CIRI by regulating the PINK1/Parkin-dependent Mitophagy pathway remains unclear and warrants further investigation. The purpose of this study is to explore the underlying mechanism through which β-ASA influences PINK1/Parkin-mediated Mitophagy in the hippocampus following ischemia-reperfusion. In the results section, the present study examined the effects of β-ASA on middle cerebral artery occlusion/reperfusion (MCAO/R)-induced neurological deficits using the Longa test and TTC staining, rats were then treated with β-ASA (20, 40, and 80 mg/kg). The findings demonstrate that β-ASA promotes functional recovery in post-ischemic stroke, as evidenced by improved neurological function, reduced infarct volume, decreased neuronal damage, and lowered neuronal Apoptosis. Furthermore, β-ASA significantly enhanced Autophagy by increasing Beclin1 expression while reducing p62 and LC3-I/LC3-II expression. Additionally, β-ASA markedly activated PINK1/Parkin-mediated Mitophagy. Finally, the introduction of Mitophagy inhibitors was employed to clarify the relationship between Autophagy and β-ASA, indicating that β-ASA promotes Autophagy by activating the PINK1/Parkin signalling pathway. In conclusion, this study elucidates that β-ASA alleviates cerebral infarction, neurological impairment, and neuronal damage by targeting PINK1/Parkin-dependent Mitophagy, thereby presenting a potential therapeutic strategy for CIRI.

Beta-asarone; Cerebral ischemia reperfusion injury (CIRI); Mitophagy; PINK1/Parkin.