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

• Published in: Biomedicine & pharmacotherapy 2024-11, Vol.180, p.117506, Article 117506
• Main Authors: He, Xingyue, Wu, Mingdian, Chen, Likun, Liu, Meijun, Hu, Xuan, Meng, Ying, Yue, Hao, Yang, Xiaoshan, Zheng, Peng, Dai, Yulin
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - pharmacology; Animals; Apoptosis - drug effects; Disease Models, Animal; Glycopeptide; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hydrogen Peroxide; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - pathology; Ischemic stroke; Ischemic Stroke - drug therapy; Ischemic Stroke - metabolism; Ischemic Stroke - pathology; Male; MCAO models; Mountain-cultivated ginseng; Neovascularization, Physiologic - drug effects; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Zebrafish
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117506

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 H2O2-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 H2O2-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, modulating factors such as Nrf2, Bcl-2, Caspase 3, eNOS, and VEGFA, thereby ameliorating cellular oxidative distress and catalyzing angiogenesis. Collectively, these results demonstrate the potential protective effects of APMCG-1 in IS pharmacotherapy and its prospective utility as an herbal-derived IS treatment modality. [Display omitted]