Liu Zihan, Han Zeyu, Bao Wenshuai, Guo Yihan, Yuan Yuan, Cheng Jianming, Zhang Jie, Hu Yang
Jiangsu Province Engineering Research Center of Classical Prescription, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Xian Jiaotong-Liverpool University, XJTLU Wisdom Lake Academy of Pharmacy, Suzhou, China.
CNS Neurosci Ther. 2025 Aug;31(8):e70559. doi: 10.1111/cns.70559.
Cerebral ischemia-reperfusion (I/R) injury is a critical pathological process in stroke, characterized by disrupted energy metabolism, inflammatory responses, and mitochondrial dysfunction. Targeting mitochondrial dynamics presents promising strategies for alleviating brain injury. This study investigates the role and mechanism of Gastrodin (Gas) in regulating mitochondrial dynamics and mitigating cerebral I/R injury via activation of the AMPK-OPA1 signaling pathway.
An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model and an in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) model were used to assess the effects of Gas on inflammation, mitochondrial function, and energy metabolism. Immunofluorescence, western blotting (WB), reverse-transcription PCR (RT-PCR), JC-1 staining, and molecular docking techniques were employed for analysis.
Gas activated the AMPK-OPA1 signaling pathway, promoting mitochondrial fusion, restoring membrane potential, enhancing ATP production, and rebalancing NAD/NADH levels. Additionally, Gas significantly suppressed I/R-induced inflammatory responses, reduced neuronal damage, and decreased infarct volume. Notably, its protective effects on mitochondrial fusion and neuroprotection were abolished under AMPK silencing, highlighting the critical role of the AMPK-OPA1 pathway.
Gas alleviates cerebral I/R injury by regulating mitochondrial dynamics via the AMPK-OPA1 signaling pathway. These findings provide a theoretical basis for the therapeutic application of Gas in stroke and offer new insights into mitochondrial-targeted treatment strategies.
脑缺血再灌注（I/R）损伤是中风的关键病理过程，其特征为能量代谢紊乱、炎症反应和线粒体功能障碍。针对线粒体动力学的研究为减轻脑损伤提供了有前景的策略。本研究探讨天麻素（Gas）通过激活AMPK-OPA1信号通路调节线粒体动力学及减轻脑I/R损伤的作用和机制。
采用体外氧糖剥夺/再灌注（OGD/R）模型和体内大脑中动脉闭塞/再灌注（MCAO/R）模型评估Gas对炎症、线粒体功能和能量代谢的影响。运用免疫荧光、蛋白质印迹法（WB）、逆转录聚合酶链反应（RT-PCR）、JC-1染色和分子对接技术进行分析。
Gas激活AMPK-OPA1信号通路，促进线粒体融合，恢复膜电位，增强ATP生成，并使NAD/NADH水平重新平衡。此外，Gas显著抑制I/R诱导的炎症反应，减少神经元损伤，减小梗死体积。值得注意的是，在AMPK沉默的情况下，其对线粒体融合和神经保护的作用被消除，突出了AMPK-OPA1通路的关键作用。
Gas通过AMPK-OPA1信号通路调节线粒体动力学来减轻脑I/R损伤。这些发现为Gas在中风治疗中的应用提供了理论依据，并为线粒体靶向治疗策略提供了新的见解。
