Akbarian Mahsan, Mirzavi Farshad, Amirahmadi Sabiheh, Hosseini Mahmoud, Alipour Mohsen, Feizi Hadi, Rajabian Arezoo
Department of Physiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Inflammopharmacology. 2022 Jun;30(3):1021-1035. doi: 10.1007/s10787-022-00971-7. Epub 2022 Mar 28.
This study aimed to investigate the effects of pomegranate (Punica granatum L.) seed hydro-ethanolic extract (PSE) on cholinergic dysfunction, neuroinflammation, and oxidative stress in the scopolamine-induced amnesic rats.
The rats were given PSE (200, 400, and 800 mg/kg, gavage) for 3 weeks. In the third week, scopolamine was administered 30 min before the Morris water maze (MWM) and passive avoidance (PA) tests. Oxidative stress indicators, acetylcholinesterase (AChE) activity, and mRNA expression of necrosis factor (TNF)-α, interleukin (IL)-1β, AChE, and M1 acetylcholine receptor (CHRM1) in the brain, were measured.
PSE reduced the time (maximum 173%) and distance (maximum 332%) required to reach the platform during MWM learning (P < 0.001). In the prob test (P < 0.001), it increased the target area time (maximum 44%) and distance (maximum 30%). PSE also increased delay and light time (maximums of 86 and 48%, respectively) (P < 0.001), while decreasing the time in dark region of PA (maximums 727%) (P < 0.001). PSE also reduced malondialdehyde and AChE in the cortex (maximum 168 and 171%, respectively) and hippocampus (maximum 151 and 182%, respectively) (P < 0.001). In the PSE-treated groups, the levels of thiol and superoxide dismutase were increased in the cortex (maximum 54 and 65%, respectively) and hippocampus (maximum 90 and 51%, respectively) (P < 0.001). TNF-α, IL-1β, and AChE expressions in the hippocampus were reduced by PSE (maximum 114, 137, and 106%, respectively, P < 0.01). Meanwhile, CHMR expression was increased (66%).
PSE successfully alleviated scopolamine-induced memory and learning deficits in rats which is probably via modulating cholinergic system function, oxidative stress, and inflammatory cytokines.
本研究旨在探讨石榴（Punica granatum L.）籽水乙醇提取物（PSE）对东莨菪碱诱导的记忆缺失大鼠胆碱能功能障碍、神经炎症和氧化应激的影响。
大鼠连续3周灌胃给予PSE（200、400和800mg/kg）。在第3周，于莫里斯水迷宫（MWM）和被动回避（PA）试验前30分钟给予东莨菪碱。检测氧化应激指标、乙酰胆碱酯酶（AChE）活性以及大脑中坏死因子（TNF）-α、白细胞介素（IL）-1β、AChE和M1型乙酰胆碱受体（CHRM1）的mRNA表达。
PSE缩短了MWM学习过程中到达平台所需的时间（最多缩短173%）和距离（最多缩短332%）（P<0.001）。在探针试验中（P<0.001），PSE增加了目标区域时间（最多增加44%）和距离（最多增加30%）。PSE还增加了延迟时间和光照时间（分别最多增加86%和48%）（P<0.001），同时减少了PA试验中在黑暗区域的时间（最多减少727%）（P<0.001）。PSE还降低了皮质（分别最多降低168%和171%）和海马体（分别最多降低151%和182%）中的丙二醛和AChE水平（P<0.001）。在PSE处理组中，皮质（分别最多增加54%和65%）和海马体（分别最多增加90%和51%）中的巯基和超氧化物歧化酶水平升高（P<0.001）。PSE降低了海马体中TNF-α、IL-1β和AChE的表达（分别最多降低114%、137%和106%，P<0.01）。同时，CHMR表达增加（66%）。
PSE成功减轻了东莨菪碱诱导的大鼠记忆和学习缺陷，这可能是通过调节胆碱能系统功能、氧化应激和炎性细胞因子实现的。
