Myrtenol improves brain damage and promotes angiogenesis in rats with cerebral infarction by activating the ERK1/2 signalling pathway

• Published in: Pharmaceutical biology Vol. 59; no. 1; pp. 582 - 591
• Main Authors: Huang, Shengming, Tan, Zhanguo, Cai, Jirui, Wang, Zhiping, Tian, Yuejun
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2021; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - pharmacology; Angiogenesis Inducing Agents - therapeutic use; Animals; Antioxidants; Apoptosis; Bcl-2 protein; Bicyclic Monoterpenes - pharmacology; Bicyclic Monoterpenes - therapeutic use; Brain damage; Brain injury; Caspase-3; Cerebral blood flow; Cerebral infarction; Cerebral Infarction - drug therapy; Cerebral Infarction - metabolism; Cerebral Infarction - pathology; Cerebral ischaemia/reperfusion; Dose-Response Relationship, Drug; Extracellular signal-regulated kinase; Fibroblast growth factor 2; Ischemia; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; middle cerebral artery occlusion; neurological deficits; Neurological diseases; Phosphorylation; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Signal transduction; Toxicity; Vascular endothelial growth factor; VEGF; neurological deficits; Cerebral ischaemia/reperfusion; VEGF; middle cerebral artery occlusion
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2021.1917626

Cerebral ischaemia/reperfusion (I/R) injury has a high disability and fatality worldwide. Myrtenol has protective effects on myocardial I/R injury through antioxidant and anti-apoptotic effects. This study investigated the effect of myrtenol on cerebral ischaemia/reperfusion (I/R) injury and the underlying mechanism. Cerebral I/R injury was induced in adult Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 90 min. MCAO rats were treated with or without myrtenol (10, 30, or 50 mg/kg/day) or/and U0126 (10 μL) intraperitoneally for 7 days. In the present study, myrtenol had no toxicity at concentrations up to 1.3 g/kg. Myrtenol treatment improved neurological function of MCAO rats, with significantly (p < 0.05) improved neurological deficits (4.31 ± 1.29 vs. 0.00) and reduced brain edoema (78.95 ± 2.27% vs. 85.48 ± 1.24%). Myrtenol extenuated brain tissue injury and neuronal apoptosis, with increased Bcl-2 expression (0.48-fold) and decreased Bax expression (2.02-fold) and caspase-3 activity (1.36-fold). Myrtenol promoted angiogenesis in the brain tissues of MCAO rats, which was reflected by increased VEGF (0.86-fold) and FGF2 (0.51-fold). Myrtenol promoted the phosphorylation of MEK1/2 (0.80-fold) and ERK1/2 (0.97-fold) in MCAO rats. U0126, the inhibitor of ERK1/2 pathway, reversed the protective effects of myrtenol on brain tissue damage and angiogenesis in MCAO rats. Myrtenol reduced brain damage and angiogenesis through activating the ERK1/2 signalling pathway, which may provide a novel alternative strategy for preventing cerebral I/R injury. Further in vitro work detailing its mechanism-of-action for improving ischaemic cerebral infarction is needed.