APMCG-1 attenuates ischemic stroke injury by reducing oxidative stress and apoptosis and promoting angiogenesis via activating PI3K/AKT pathway

作者：Xingyue He, Mingdian Wu, Li-kun Chen, Meijun Liu, Xuan Hu, Ying Meng, Hao Yue, Xiaoshan Yang, Peng Zheng, Yulin Dai · 发表于：Biomedicine & Pharmacotherapy · 年份：2024 · DOI：10.1016/j.biopha.2024.117506 · 被引用次数：14 · 研究领域：Neurological Disease Mechanisms and Treatments、Neuroinflammation and Neurodegeneration Mechanisms、Autophagy in Disease and Therapy

Ischemic stroke (IS) is a major cause of mortality and morbidity worldwide. Beyond thrombolysis, strategies targeting anti-oxidative apoptosis and angiogenesis are considered prospective therapeutic strategies. Nevertheless, existing natural and clinical remedies have limited efficacy in the management of IS. Moreover, despite their millennial legacy of IS remediation, natural remedies such as ginseng incur high production costs. The novel glycopeptide APMCG-1, extracted from mountain-cultivated ginseng dregs in our previous study, is a potent therapeutic candidate for IS. This study investigated APMCG-1's remedial mechanisms against IS injury using an H 2 O 2 -induced oxidative stress paradigm in human umbilical vein endothelial cells (HUVECs) emulating ischemic endothelial cells, in a ponatinib-induced zebrafish IS model, and in rat middle cerebral artery occlusion (MCAO) prototypes. Cellular assays confirmed the proficiency of APMCG-1 in preventing oxidative stress and cell death, fostering regeneration, and facilitating neovascularization within the H 2 O 2 -stressed HUVECs framework. Moreover, APMCG-1 augmented hemodynamic velocity, oxidative stress mitigation, apoptosis reduction, and motor enhancement in a zebrafish model of IS. In MCAO rats, APMCG-1 ameliorated neurological deficits and cerebral injury, as evidenced by increased neurological scores and diminished infarct dimensions. In cells and animal models, APMCG-1 activated the PI3K/AKT signaling pathway, modulati...