Azizi Zahra, Ebrahimi Shima, Saadatfar Elshaan, Kamalinejad Mohammad, Majlessi Nahid
Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.
Behav Pharmacol. 2012 Jun;23(3):241-9. doi: 10.1097/FBP.0b013e3283534301.
This study evaluated the efficacy of thymol and carvacrol against cognitive deficits induced by amyloid β (Aβ) or scopolamine. Rats received bilateral intrahippocampal injections of Aβ(25-35) or intraperitoneal injections of scopolamine, and the effect of different doses of thymol, or carvacrol (0.5, 1, or 2 mg/kg) on cognitive function was determined. Animals were subjected to 5 days of training in the Morris water maze: 4 days with an invisible platform to test spatial learning and the 5th day with a visible platform to test motivation and sensorimotor coordination. The acute toxicities of thymol and carvacrol were also studied. The results showed increases in escape latency and decreases in target quadrant entries in Aβ or scopolamine-treated groups. These impairments were reversed by pretraining administration of either thymol or carvacrol. The calculated LD50's of thymol (565.7 mg/kg) and carvacrol (471.2 mg/kg) were found to be much higher than their therapeutic doses (thymol 0.5 mg/kg, carvacrol 1 mg/kg). These findings provide preliminary positive evidence for the effectiveness and safety of thymol and carvacrol in alleviating cognitive impairments caused by increased Aβ levels or cholinergic hypofunction. Anticholinesterase, antioxidant, and anti-inflammatory activities may be the mechanisms contributing toward their beneficial effects in these models.
本研究评估了百里香酚和香芹酚对由淀粉样蛋白β（Aβ）或东莨菪碱诱导的认知缺陷的疗效。大鼠接受双侧海马内注射Aβ（25 - 35）或腹腔注射东莨菪碱，并测定不同剂量的百里香酚或香芹酚（0.5、1或2 mg/kg）对认知功能的影响。动物在莫里斯水迷宫中接受5天训练：前4天使用不可见平台测试空间学习能力，第5天使用可见平台测试动机和感觉运动协调能力。还研究了百里香酚和香芹酚的急性毒性。结果显示，Aβ或东莨菪碱处理组的逃避潜伏期增加，目标象限进入次数减少。预先给予百里香酚或香芹酚可逆转这些损伤。计算得出百里香酚的半数致死量（LD50）为565.7 mg/kg，香芹酚的半数致死量为471.2 mg/kg，发现它们远高于治疗剂量（百里香酚0.5 mg/kg，香芹酚1 mg/kg）。这些发现为百里香酚和香芹酚在减轻由Aβ水平升高或胆碱能功能减退引起的认知障碍方面的有效性和安全性提供了初步的积极证据。抗胆碱酯酶、抗氧化和抗炎活性可能是它们在这些模型中产生有益作用的机制。
