Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104977. doi: 10.1016/j.jstrokecerebrovasdis.2020.104977. Epub 2020 Jun 13.
Ischemic stroke is a severe neurological disorder that affected millions of people worldwide. Neuro-inflammation and apoptosis play an essential role in the pathogenesis of neuronal death during ischemic stroke. Alpha-pinene is a bicyclic terpenoid with anti-inflammatory and anti-apoptotic activities. Accordingly, the main purpose of this study was to assess the protective effect of α-pinene in ischemic stroke.
To induce ischemic stroke in male Wistar rats, the middle cerebral artery was occluded for 60 min followed by 24 h reperfusion. Alpha-pinene was injected intraperitoneally at the beginning of reperfusion. A day after reperfusion, the neurological deficits, volume of infarct area, and blood-brain barrier (BBB) permeability were evaluated. The mRNA expression of inflammatory cytokines as well as pro- and anti-apoptotic genes was assessed by using reverse transcription-polymerase chain reaction. The protein levels of inflammatory cytokines were also measured by ELISA method.
The results showed that α-pinene (50 and 100 mg/kg) significantly improved sensorimotor function and decreased the volume of infarct area in the brain. The high permeability of BBB was also alleviated by α-pinene (50 and 100 mg/kg) in ischemic areas. Besides, α-pinene (100 mg/kg) attenuated neuro-inflammation through decreasing both the gene and protein expression of TNF-α and IL-1β in the hippocampus, cortex, and striatum. Besides, α-pinene (100 mg/kg) suppressed apoptosis via downregulation of the pro-apoptotic Bax mRNA expression with a concomitant upregulation of anti-apoptotic Bcl-2 gene expression.
Overall, it was concluded that α-pinene exerts neuroprotective effect during ischemic stroke through attenuating neuroinflammation and inhibition of apoptosis.
缺血性中风是一种严重的神经系统疾病,影响了全球数百万人。神经炎症和细胞凋亡在缺血性中风导致神经元死亡的发病机制中起着重要作用。α-蒎烯是一种具有抗炎和抗凋亡作用的双环萜烯。因此,本研究的主要目的是评估α-蒎烯对缺血性中风的保护作用。
雄性 Wistar 大鼠通过大脑中动脉阻塞 60 分钟再灌注 24 小时来诱导缺血性中风。α-蒎烯在再灌注开始时腹腔内注射。再灌注后 1 天,评估神经功能缺损、梗死面积体积和血脑屏障(BBB)通透性。通过逆转录-聚合酶链反应评估炎症细胞因子以及促凋亡和抗凋亡基因的 mRNA 表达。还通过 ELISA 法测量炎症细胞因子的蛋白水平。
结果表明,α-蒎烯(50 和 100mg/kg)显著改善了感觉运动功能,减少了大脑中的梗死面积。α-蒎烯(50 和 100mg/kg)还减轻了缺血区 BBB 的高通透性。此外,α-蒎烯(100mg/kg)通过降低海马、皮质和纹状体中 TNF-α 和 IL-1β 的基因和蛋白表达来减轻神经炎症。此外,α-蒎烯(100mg/kg)通过下调促凋亡 BaxmRNA 表达并同时上调抗凋亡 Bcl-2 基因表达来抑制细胞凋亡。
总的来说,α-蒎烯通过减轻神经炎症和抑制细胞凋亡在缺血性中风中发挥神经保护作用。