Naik Bhagyashree, Nirwane Abhijit, Majumdar Anuradha
Department of Pharmacology, Bombay College of Pharmacy, Mumbai, 400098 India.
Cogn Neurodyn. 2017 Feb;11(1):35-49. doi: 10.1007/s11571-016-9413-1. Epub 2016 Sep 30.
There is strong evidence that mitochondrial dysfunction mediated oxidative stress results in aging and energy metabolism deficits thus playing a prime role in pathogenesis of Alzheimer's disease, neuronal death and cognitive dysfunction. Evidences accrued in empirical studies suggest the antioxidant, anticancer and anti-inflammatory activities of the phytochemical pterostilbene (PTS). PTS also exhibits favourable pharmacokinetic attributes compared to other stilbenes. Hence, in the present study, we explored the neuroprotective role of PTS in ameliorating the intracerebroventricular administered streptozotocin (STZ) induced memory decline in rats. PTS at doses of 10, 30 and 50 mg/kg, was administered orally to STZ administered Sprague-Dawley (SD) rats. The learning and memory tests, Morris water maze test and novel object recognition test were performed which revealed improved cognition on PTS treatment. Further, there was an overall improvement in brain antioxidant parameters like elevated catalase and superoxide dismutase activities, GSH levels, lowered levels of nitrites, lipid peroxides and carbonylated proteins. There was improved cholinergic transmission as evident by decreased acetylcholinesterase activities. The action of ATPases (Na K, Ca and Mg) indicating the maintenance of cell membrane potential was also augmented. mRNA expression of battery of genes involved in cellular mitochondrial biogenesis and inflammation showed variations which extrapolate to hike in mitochondrial biogenesis and abated inflammation. The histological findings corroborated the effective role of PTS in countering STZ induced structural aberrations in brain.
有强有力的证据表明,线粒体功能障碍介导的氧化应激会导致衰老和能量代谢缺陷,从而在阿尔茨海默病、神经元死亡和认知功能障碍的发病机制中起主要作用。实证研究积累的证据表明,植物化学物质紫檀芪(PTS)具有抗氧化、抗癌和抗炎活性。与其他芪类化合物相比,PTS还具有良好的药代动力学特性。因此,在本研究中,我们探讨了PTS在改善脑室内注射链脲佐菌素(STZ)诱导的大鼠记忆衰退中的神经保护作用。将剂量为10、30和50mg/kg的PTS口服给予注射STZ的Sprague-Dawley(SD)大鼠。进行了学习和记忆测试、莫里斯水迷宫测试和新物体识别测试,结果显示PTS治疗后认知能力有所改善。此外,脑抗氧化参数总体有所改善,如过氧化氢酶和超氧化物歧化酶活性升高、谷胱甘肽水平升高、亚硝酸盐、脂质过氧化物和羰基化蛋白质水平降低。乙酰胆碱酯酶活性降低表明胆碱能传递得到改善。表明细胞膜电位维持的ATP酶(钠钾、钙和镁)的活性也增强。参与细胞线粒体生物发生和炎症的一系列基因的mRNA表达出现变化,这推断出线粒体生物发生增加和炎症减轻。组织学结果证实了PTS在对抗STZ诱导脑结构异常方面的有效作用。