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

Abstract

Context: 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.Objective: This study investigated the effect of myrtenol on cerebral ischaemia/reperfusion (I/R) injury and the underlying mechanism. Materials and methods: 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 lL) intraperitoneally for 7 days. Results: 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. Discussion and conclusions: 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.

Myrtenol Ameliorates Recognition Memories’ Impairment and Anxiety-Like Behaviors Induced by Asthma by Mitigating Hippocampal Inflammation and Oxidative Stress in Rats

“…The anxiolytic effects of myrtenol have been demonstrated in some tasks, including open field, plus maze, and light-dark compartment tasks [29,77]. It seems that myrtenol's effects on CNS are driven by the ease with which it can cross the blood-cerebrospinal barrier [73,78,79].…”

Increasing the Efficacy of Treatment of Staphylococcus aureus–Candida albicans Mixed Infections with Myrtenol

“…The lack of toxicity of terpenes [ 56 , 57 ] makes them a harmless and potential therapeutic agent to increase the efficiency of the treatment of bacterial and fungal infections mediated by resistant strains. Thus, in much previous research, neither cytotoxicity nor acute toxicity on animals has been found for relatively high concentrations of myrtenol, up to 600 mg/L in vitro and 1.3 g per kg in vivo [ 58 , 59 , 60 ]. It is worth mentioning that a crucial benefit from using the described compounds is that their resource is almost inexhaustible [ 61 , 62 ].…”

Inhibitory Effect of (-)-myrtenol alone and in combination with antifungal agents on Candida spp.

“…One of the main sources of search is natural products and their derivatives, such as bicyclic monoterpene alcohols that have been shown to have several biological effects in the literature. (Nikitina et al, 2021) (-) Myrtenol is an example of this group with several reported biological effects in literature: angiogenesis (Huang et al, 2021), gastric protector (Viana et al, 2019), anti-bacterial (Cordeiro et al, 2020). Thus, the aim of this study was to examine the effects of myrtenol alone and in combination with antifungal drugs against Candida spp.…”