香芹酚可降低大鼠弥漫性外伤性脑损伤后的血脑屏障通透性。
Carvacrol decreases blood-brain barrier permeability post-diffuse traumatic brain injury in rats.
机构信息
Institute of Basic and Clinical Physiology Sciences, Endocrinology and Metabolism Research Center, Kerman, Iran.
Institute of Neuropharmacology, Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran.
出版信息
Sci Rep. 2023 Sep 4;13(1):14546. doi: 10.1038/s41598-023-40915-x.
Previously, we showed that Satureja Khuzestanica Jamzad essential oil (SKEO) and its major component, carvacrol (CAR), 5-isopropyl-2-methylphenol, has anti-inflammatory, anti-apoptotic, and anti-edematous properties after experimental traumatic brain injury (TBI) in rats. CAR, predominantly found in Lamiaceae family (Satureja and Oregano), is lipophilic, allowing diffusion across the blood-brain barrier (BBB). These experiments test the hypothesis that acute treatment with CAR after TBI can attenuate oxidative stress and BBB permeability associated with CAR's anti-edematous traits. Rats were divided into six groups and injured using Marmarou weight drop: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg) and CAR200-naive treated rats. Intraperitoneal injection of vehicle or CAR was administered thirty minutes after TBI induction. 24 h post-injury, brain edema, BBB permeability, BBB-related protein levels, and oxidative capacity were measured. Data showed CAR 200 mg/kg treatment decreased brain edema and prevented BBB permeability. CAR200 decreased malondialdehyde (MDA) and reactive oxygen species (ROS) and increased superoxide dismutase (SOD) and total antioxidative capacity (T-AOC), indicating the mechanism of BBB protection is, in part, through antioxidant activity. Also, CAR 200 mg/kg treatment suppressed matrix metalloproteinase-9 (MMP-9) expression and increased ZO-1, occludin, and claudin-5 levels. These data indicate that CAR can promote antioxidant activity and decrease post-injury BBB permeability, further supporting CAR as a potential early therapeutic intervention that is inexpensive and more readily available worldwide. However, more experiments are required to determine CAR's long-term impact on TBI pathophysiology.
先前,我们发现 Satureja Khuzestanica Jamzad 精油(SKEO)及其主要成分,对异丙基-2-甲基苯酚(carvacrol,CAR),具有抗炎、抗细胞凋亡和抗水肿的特性,可减轻实验性创伤性脑损伤(TBI)后大鼠的炎症反应。CAR 主要存在于唇形科(牛至和迷迭香)中,脂溶性使其能够扩散穿过血脑屏障(BBB)。这些实验检验了以下假设:在 TBI 后急性给予 CAR 治疗可以减轻与 CAR 抗水肿特性相关的氧化应激和 BBB 通透性。大鼠被分为六组,采用 Marmarou 重物坠落法造成创伤:假手术组、TBI 组、TBI+载体组、TBI+CAR(100 和 200mg/kg)组和 CAR200-未处理组。TBI 诱导后 30 分钟进行腹腔注射载体或 CAR。伤后 24 小时,测量脑水肿、BBB 通透性、BBB 相关蛋白水平和氧化能力。数据显示,CAR 200mg/kg 治疗可降低脑水肿并防止 BBB 通透性增加。CAR200 降低了丙二醛(MDA)和活性氧(ROS)的水平,增加了超氧化物歧化酶(SOD)和总抗氧化能力(T-AOC),表明 BBB 保护的机制部分是通过抗氧化活性。此外,CAR 200mg/kg 治疗抑制了基质金属蛋白酶-9(MMP-9)的表达,并增加了 ZO-1、occludin 和 claudin-5 的水平。这些数据表明,CAR 可促进抗氧化活性并降低损伤后 BBB 通透性,进一步支持 CAR 作为一种具有成本效益且在全球范围内更容易获得的潜在早期治疗干预手段。然而,还需要更多实验来确定 CAR 对 TBI 病理生理学的长期影响。