Kouhestani Somayeh, Jafari Adele, Babaei Parvin
Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences; Department of Physiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Department of Physiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Neural Regen Res. 2018 Oct;13(10):1827-1832. doi: 10.4103/1673-5374.238714.
Alzheimer's disease (AD) is associated with oxidative stress, and ultimately results in cognitive deficit. Despite existing literature on the pathophysiology of AD, there is currently no cure for AD. The present study investigated the effects of kaempferol (Kmp) isolated from the extract of Mespilus germanica L. (medlar) leaves on cognitive impairment, hippocampal antioxidants, apoptosis, lipid peroxidation and neuro-inflammation markers in ovariectomized (OVX) rat models of sporadic AD. Kaempferol, as the main flavonoid of medlar extract has been previously known for anti-oxidative, anti-inflammatory and anti-neurotoxic effects. Thirty-two female Wistar rats were ovariectomized, and randomly divided into four groups: sham, OVX + saline, OVX + streptozotocin (STZ) + saline, OVX + STZ + Kmp. Animals received intracerebroventricular injection of STZ (3 mg/kg, twice with one day interval) to establish models of sporadic AD. Intraperitoneal injection of Kmp (10 mg/kg) for 21 days was performed in the OVX + STZ + Kmp group. Spatial learning and memory of rats were evaluated using a Morris water maze. Finally, brain homogenates were used for biochemical analysis by enzyme-linked immunosorbent assay. The results showed a significant improvement in spatial learning and memory as evidenced by shortened escape latency and searching distance in Morris water maze in the OVX + STZ + Kmp group compared with the OVX + STZ group. Kmp also exhibited significant elevations in brain levels of antioxidant enzymes of superoxide dismutase and glutathione, while reduction in tumor necrosis factor-α and malondialdehyde. Our results demonstrate that Kmp is capable of alleviating STZ-induced memory impairment in OVX rats, probably by elevating endogenous hippocampal antioxidants of superoxide dismutase and glutathione, and reducing neuroinflammation. This study suggests that Kmp may be a potential neuroprotective agent against cognitive deficit in AD.
阿尔茨海默病（AD）与氧化应激相关，最终导致认知缺陷。尽管现有关于AD病理生理学的文献，但目前尚无治愈AD的方法。本研究调查了从欧楂（Mespilus germanica L.）叶提取物中分离出的山奈酚（Kmp）对散发性AD卵巢切除（OVX）大鼠模型认知障碍、海马抗氧化剂、细胞凋亡、脂质过氧化和神经炎症标志物的影响。山奈酚作为欧楂提取物的主要黄酮类化合物，此前已因具有抗氧化、抗炎和抗神经毒性作用而闻名。将32只雌性Wistar大鼠进行卵巢切除，并随机分为四组：假手术组、OVX + 生理盐水组、OVX + 链脲佐菌素（STZ）+ 生理盐水组、OVX + STZ + Kmp组。动物接受脑室内注射STZ（3 mg/kg，间隔一天注射两次）以建立散发性AD模型。在OVX + STZ + Kmp组中进行腹腔注射Kmp（10 mg/kg），持续21天。使用Morris水迷宫评估大鼠的空间学习和记忆能力。最后，通过酶联免疫吸附测定法对脑匀浆进行生化分析。结果显示，与OVX + STZ组相比，OVX + STZ + Kmp组在Morris水迷宫中的逃避潜伏期和搜索距离缩短，表明空间学习和记忆有显著改善。Kmp还使超氧化物歧化酶和谷胱甘肽等抗氧化酶的脑水平显著升高，同时降低肿瘤坏死因子-α和丙二醛水平。我们的结果表明，Kmp能够减轻STZ诱导的OVX大鼠记忆障碍，可能是通过提高内源性海马超氧化物歧化酶和谷胱甘肽抗氧化剂水平以及减轻神经炎症来实现的。本研究表明，Kmp可能是一种针对AD认知缺陷的潜在神经保护剂。
