Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
J Mol Neurosci. 2013 Nov;51(3):813-9. doi: 10.1007/s12031-013-0069-6. Epub 2013 Jul 23.
Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been demonstrated to possess various biological actions. The present study was designed to investigate the neuroprotective effect of CAR on diabetes-associated cognitive deficit (DACD) in a rat model of diabetes and exploring its potential molecular mechanism. Diabetic rats were treated with CAR by the doses of 25, 50, and 100 mg/kg for 7 weeks. Morris water maze was used for behavioral evaluation of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of oxidative stress (MDA, SOD, and GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3. After 7 weeks of streptozotocin injection, the rats produced remarkable increase in escape latency, coupled with increased oxidative stress (increased MDA level and decreased SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3 in different regions of diabetic rat brain. Interestingly, coadministration of CAR significantly and dose-dependently prevented behavioral, biochemical, and molecular changes associated with diabetes. In summary, our findings provide the first evidence that CAR can remarkably attenuate DACD and suggest the involvement of oxidative stress, inflammation, and apoptotic cascades in the development of cognitive impairment caused by diabetes. The pharmacological effect of CAR suggests that it may be used as a promising agent for the treatment of conventional antihyperglycemic regiments as well as DACD.
香芹酚 (CAR) 是一种天然存在的酚类单萜烯，已被证明具有多种生物活性。本研究旨在探讨 CAR 对糖尿病相关认知障碍 (DACD) 的神经保护作用，并探索其潜在的分子机制。糖尿病大鼠用 25、50 和 100mg/kg 的剂量 CAR 治疗 7 周。通过 Morris 水迷宫对记忆进行行为评估。制备大脑皮质和海马的细胞质和核部分，以定量测定氧化应激 (MDA、SOD 和 GSH)、NF-κB p65 单位、TNF-α、IL-1β 和 caspase-3。在链脲佐菌素注射 7 周后，糖尿病大鼠的逃避潜伏期明显增加，同时大脑不同区域的氧化应激（MDA 水平升高，SOD 和 GSH 降低）、NF-κB p65 单位、TNF-α、IL-1β 和 caspase-3 也增加。有趣的是，CAR 的共同给药可显著且剂量依赖性地预防与糖尿病相关的行为、生化和分子变化。综上所述，我们的研究结果首次提供了 CAR 可显著减轻 DACD 的证据，并表明氧化应激、炎症和凋亡级联在糖尿病引起的认知障碍发展中起作用。CAR 的药理学作用表明，它可能被用作治疗常规抗高血糖药物和 DACD 的有前途的药物。
