Wang Yujiao, Xie Daojun, Ma Shijia, Wang Yuhe, Zhang Chengcheng, Chen Zhuyue
The First Clinical Medical College of Anhui University of Chinese Medicine, 230036, Hefei, Anhui, China.
Encephalopathy Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230036, Hefei, Anhui, China.
Eur J Pharmacol. 2025 Sep 5;1002:177831. doi: 10.1016/j.ejphar.2025.177831. Epub 2025 Jun 7.
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.
脑缺血再灌注损伤（CIRI）是指当血流恢复至脑组织时发生的继发性脑损伤类型；它是导致残疾和死亡的主要因素之一。PINK1/ Parkin介导的线粒体自噬激活在CIRI过程中发挥神经保护作用。β-细辛醚（β-ASA）是石菖蒲、川芎等传统天然药物的主要活性成分，具有抗炎、抗氧化和增强自噬的特性。然而，β-ASA是否能通过调节PINK1/ Parkin依赖的线粒体自噬途径改善CIRI仍不清楚，值得进一步研究。本研究的目的是探讨β-ASA影响缺血再灌注后海马中PINK1/ Parkin介导的线粒体自噬的潜在机制。在结果部分，本研究使用Longa试验和TTC染色检测了β-ASA对大脑中动脉闭塞/再灌注（MCAO/R）诱导的神经功能缺损的影响，然后用β-ASA（20、40和80mg/kg）处理大鼠。研究结果表明，β-ASA可促进缺血性中风后的功能恢复，表现为神经功能改善、梗死体积减小、神经元损伤减轻和神经元凋亡减少。此外，β-ASA通过增加Beclin1表达同时降低P62和LC3-I/LC3-II表达显著增强自噬。此外，β-ASA显著激活PINK1/ Parkin介导的线粒体自噬。最后，使用线粒体自噬抑制剂来阐明自噬与β-ASA之间的关系，表明β-ASA通过激活PINK1/ Parkin信号通路促进自噬。总之，本研究阐明β-ASA通过靶向PINK1/ Parkin依赖的线粒体自噬减轻脑梗死、神经功能障碍和神经元损伤，从而为CIRI提供了一种潜在的治疗策略。
