Hussein Hagar M, Abdel Kawy Mostafa A, Eltanany Basma M, Pont Laura, Benavente Fernando, Fayez Ahmed M, Alnajjar Radwan, Al-Karmalawy Ahmed A, Abdelmonem Azza R, Mohsen Engy
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University Cairo 11562 Egypt
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Cairo University Cairo 11562 Egypt.
RSC Adv. 2024 Dec 23;14(54):40267-40286. doi: 10.1039/d4ra06991a. eCollection 2024 Dec 17.
Many plants are reported to enhance cognition in amnesic-animal models. The metabolite profile of fruit methanolic extract (CDFME) was characterized by LC-QTOF-MS/MS, and its total phenolics content (TPC) and total flavonoids content (TFC) were determined. In parallel, its cognitive-enhancing effect on scopolamine (SCOP)-induced AD in rats was evaluated. The TPC and TFC were 44.75 ± 1.84 mg gallic acid equiv. g sample and 5.66 ± 0.67 mg rutin equiv. g sample, respectively. In total, 81 metabolites were identified, including phenolic acids, lignans, coumarins, amino acids, fatty acids, and their derivatives, fatty acid amides, polar lipids, terpenoids, and others. The most abundant metabolites identified were quinic acid, caffeoyl-4'-hydroxyphenyllactate, rosmarinic acid, and oleamide. CDFME (200 mg kg) was found to significantly enhance recognition memory in the novel object recognition test. Furthermore, it nearly corrected acetylcholinesterase (AChE), acetylcholine, noradrenaline, and dopamine hippocampal levels, which changed due to SCOP. Further validation of the results was conducted, focusing on the most abundant metabolites. Molecular docking showed that rosmarinic acid, caffeoyl-4'-hydroxyphenyllactate, sebestenoid C, and sagerinic acid exhibited the greatest affinity for receptor binding against AChE. However, molecular dynamics and mechanics calculations clarified that the complex of caffeoyl-4'-hydroxyphenyllactate with AChE was the most stable one. This study represents the first comprehensive metabolite profiling of CDFME to assess its cognition-enhancing effect both and . These results demonstrate that CDFME protects against SCOP-induced cognitive impairment. Thus, additional preclinical and clinical studies on CDFME may provide an attractive approach in pharmacotherapy and AD prophylaxis.
据报道，许多植物可增强失忆动物模型的认知能力。采用液相色谱-四极杆飞行时间串联质谱（LC-QTOF-MS/MS）对水果甲醇提取物（CDFME）的代谢物谱进行了表征，并测定了其总酚含量（TPC）和总黄酮含量（TFC）。同时，评估了其对东莨菪碱（SCOP）诱导的大鼠阿尔茨海默病（AD）的认知增强作用。TPC和TFC分别为44.75±1.84毫克没食子酸当量/克样品和5.66±0.67毫克芦丁当量/克样品。共鉴定出81种代谢物，包括酚酸、木脂素、香豆素、氨基酸、脂肪酸及其衍生物、脂肪酸酰胺、极性脂质、萜类化合物等。鉴定出的最丰富的代谢物为奎尼酸、咖啡酰-4'-羟基苯乳酸、迷迭香酸和油酰胺。发现CDFME（200毫克/千克）在新物体识别试验中显著增强识别记忆。此外，它几乎纠正了因SCOP而改变的乙酰胆碱酯酶（AChE）、乙酰胆碱、去甲肾上腺素和多巴胺海马水平。针对最丰富的代谢物对结果进行了进一步验证。分子对接表明，迷迭香酸、咖啡酰-4'-羟基苯乳酸、海芒果甾醇C和沙格酸对AChE受体结合表现出最大亲和力。然而，分子动力学和力学计算表明，咖啡酰-4'-羟基苯乳酸与AChE的复合物是最稳定的。本研究首次对CDFME进行了全面的代谢物谱分析，以评估其认知增强作用。这些结果表明，CDFME可预防SCOP诱导的认知障碍。因此，对CDFME进行更多的临床前和临床研究可能为药物治疗和AD预防提供一种有吸引力的方法。
