Neuropharmacology Division, Department of Pharmacology, I. S. F. College of Pharmacy, Moga, Punjab, 142001, India.
Mol Neurobiol. 2017 Nov;54(9):6670-6680. doi: 10.1007/s12035-016-0182-y. Epub 2016 Oct 15.
Embelin, the main active constituent of Embelia ribes, has been reported to possess various pharmacological actions, including anti-inflammatory, antioxidant, anticonvulsant, and neuroprotective. The present study was designed to investigate neuroprotective mechanisms and therapeutic potential of embelin against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic dementia in rats. STZ was infused bilaterally at the dose of (3 mg/kg/1 μl/1 min) ICV on day first and third. Spatial and non-spatial memory was evaluated using Morris water maze and object recognition task in rats. Embelin (2.5, 5, and 10 mg/kg, i.p.) was administrated for 14 days from seventh day onwards after first ICV-STZ infusion in rats. On day 22, rats were sacrificed and hippocampal brain regions were used to identify biochemical, neurochemical, and neuroinflammatory alterations. STZ-infused rats showed significant learning and memory deficit which was associated with an increase in oxidative stress (lipid peroxidation and nitrite), compromised antioxidant defense (reduced glutathione), neurotransmitter alterations (AChE, dopamine, noradrenaline, 5-hydroxytryptamine, gama amino butyric acid, and glutamate), and elevation in neuroinflammatory cytokine (IL-1 β, IL-6, and TNF-α) levels. Embelin dose dependently attenuated STZ-induced cognitive deficit and biochemical alterations and restored hippocampal neurochemical levels. The observed protective effect might be attributed to the antioxidant and anti-inflammatory potential of embelin and its ability to restore hippocampal neurochemistry. Thus, the outcomes of the current study suggest therapeutic potential of embelin in cognitive disorders such as sporadic Alzheimer's disease (SAD).
鞣料云实属中的主要活性成分鞣花酸已被报道具有多种药理作用,包括抗炎、抗氧化、抗惊厥和神经保护作用。本研究旨在探讨鞣花酸对脑室注射链脲佐菌素(ICV-STZ)诱导的实验性散发性痴呆大鼠的神经保护机制和治疗潜力。STZ 以双侧脑室(3mg/kg/1μl/1min)的剂量在第一天和第三天输注。通过 Morris 水迷宫和物体识别任务评估大鼠的空间和非空间记忆。鞣花酸(2.5、5 和 10mg/kg,腹腔注射)从第一次 ICV-STZ 输注后第 7 天开始连续 14 天给药。第 22 天,处死大鼠,使用海马脑区鉴定生化、神经化学和神经炎症改变。STZ 输注大鼠表现出明显的学习和记忆缺陷,这与氧化应激增加(脂质过氧化和亚硝酸盐)、抗氧化防御受损(还原型谷胱甘肽减少)、神经递质改变(乙酰胆碱酯酶、多巴胺、去甲肾上腺素、5-羟色胺、γ-氨基丁酸和谷氨酸)和神经炎症细胞因子(IL-1β、IL-6 和 TNF-α)水平升高有关。鞣花酸呈剂量依赖性减弱 STZ 诱导的认知缺陷和生化改变,并恢复海马神经化学水平。观察到的保护作用可能归因于鞣花酸的抗氧化和抗炎潜力及其恢复海马神经化学的能力。因此,本研究的结果表明鞣花酸在认知障碍(如散发性阿尔茨海默病)中的治疗潜力。