Ambamba Bruno Dupon Akamba, Ella Fils Armand, Ngoumen Dany Joël Ngassa, Youovop Janvier Aime Fotso, Takuissu Guy Roussel Nguemto, Dibacto Ruth Edwige Kemadjou, Fonkoua Martin, Mandob Damaris Enyegue, Djiogue Sefirin, Ngondi Judith Laure
Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaounde, Cameroon.
Center of Nutrition and Functional Foods, P.O. Box 8024, Yaounde, Cameroon.
Metab Brain Dis. 2025 Jan 14;40(1):98. doi: 10.1007/s11011-024-01521-6.
Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days. TeMac™ at 400 mg/kg body weight was orally administrated 60 min after scopolamine. Donepezil was used as a reference drug. The cognitive deficits were assessed by the Morris Water Maze and novel object recognition tests. After killing the rats, brains were immediately collected and used to carry out cholinesterase enzyme activity and histopathological analyses. Liquid chromatography-mass spectrometry (LC-MS) characterization of the TeMac™ was carried out and the identified molecules were tested in silico for their ability to cross the Blood-Brain Barrier (BBB) and inhibit acetylcholinesterase using molecular docking. The administration of the TeMac™ led to the prevention of memory deficits in rats by reducing significantly the cholinesterase enzymes activities and protecting against morphological alterations and loss of neurons in hippocampus. Seven major compounds were identified in TeMac™. Molecular docking simulations confirm the ability of oleaterminaloic acid B and stigmasterol to cross the BBB and interact with peripheral site and the acyl pocket of acetylcholinesterase. All these observations suggest that TeMac™ can therefore be used as an alternative for the management of AD-related cognitive impairments.
阿尔茨海默病（AD）与认知障碍相关，而认知障碍与胆碱能功能缺陷有关。本研究的目的是评估TeMac™在东莨菪碱诱导的阿尔茨海默病大鼠模型中预防记忆障碍的能力，并通过计算机模拟方法鉴定TeMac™中抑制乙酰胆碱酯酶的分子。通过对雄性Wistar大鼠连续7天腹腔注射东莨菪碱（1mg/kg/天）诱导胆碱能认知功能障碍。在注射东莨菪碱60分钟后，口服给予体重400mg/kg的TeMac™。多奈哌齐用作参比药物。通过莫里斯水迷宫和新物体识别试验评估认知缺陷。处死大鼠后，立即收集大脑并用于进行胆碱酯酶活性和组织病理学分析。对TeMac™进行液相色谱-质谱（LC-MS）表征，并使用分子对接在计算机上测试鉴定出的分子穿越血脑屏障（BBB）和抑制乙酰胆碱酯酶的能力。TeMac™的给药通过显著降低胆碱酯酶活性以及预防海马体中的形态学改变和神经元丢失，从而预防了大鼠的记忆缺陷。在TeMac™中鉴定出七种主要化合物。分子对接模拟证实了油酰基氨基油酸B和豆甾醇穿越血脑屏障并与乙酰胆碱酯酶的外周位点和酰基口袋相互作用的能力。所有这些观察结果表明，TeMac™因此可作为治疗AD相关认知障碍的替代药物。
