Chiroma Samaila Musa, Baharuldin Mohamad Taufik Hidayat, Mat Taib Che Norma, Amom Zulkhairi, Jagadeesan Saravanan, Ilham Adenan Mohd, Mahdi Onesimus, Moklas Mohamad Aris Mohd
Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Maiduguri, 600230 Maiduguri, Borno State, Nigeria.
Toxics. 2019 Mar 30;7(2):19. doi: 10.3390/toxics7020019.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl₃-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl₃ 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats' was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl₃ exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl₃ improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.
阿尔茨海默病(AD)是一种具有胆碱能功能障碍和氧化还原稳态受损的进行性神经退行性疾病。植物(CA)因其营养益处以及促进健康、增强认知和神经保护作用的草药配方而闻名。本研究旨在探讨CA对D-半乳糖/氯化铝诱导的大鼠认知缺陷的保护作用。将大鼠分为六组,分别给予多奈哌齐1 mg/kg/天、CA(200、400和800 mg/kg/天)以及D-半乳糖60 mg/kg/天 + 氯化铝200 mg/kg/天,持续10周。通过莫里斯水迷宫试验评估大鼠的行为学。采用酶联免疫吸附测定(ELISA)法测定海马和大脑皮层中乙酰胆碱酯酶(AChE)、磷酸化tau(P-tau)、丙二醛(MDA)的水平以及超氧化物歧化酶(SOD)的活性。此外,使用透射电子显微镜(TEM)观察大鼠前额叶皮层的超微结构。给予D-半乳糖/氯化铝的大鼠表现出认知缺陷、SOD活性降低以及AChE和MDA水平显著升高。此外,观察到前额叶皮层超微结构有明显改变。相反,CA与D-半乳糖/氯化铝联合给药可改善认知障碍、降低AChE水平、减轻海马和大脑皮层的氧化应激,并防止前额叶皮层神经元的超微结构改变。无论给予何种剂量的CA,其保护作用均与多奈哌齐相当。总之,本研究表明CA通过恢复胆碱能功能、减轻氧化应激和防止形态异常来减轻大鼠的认知缺陷。