Atef Fatma, Abdelkawy Mostafa A, Eltanany Basma M, Pont Laura, Fayez Ahmed M, Abdelhameed Mohamed F, Benavente Fernando, Younis Inas Y, Otify Asmaa M
Boulaq El-dakrour general hospital, Giza, 12617, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Sci Rep. 2025 Jan 5;15(1):859. doi: 10.1038/s41598-024-82265-2.
Alzheimer's disease (AD) poses a global health challenge, demanding innovative approaches for effective treatments. Clerodendrum infortunatum Linn. (Lamiaceae) is a shrub traditionally used as a medicinal plant to treat inflammation, skin diseases, and bronchitis. This study aims to identify the main bioactive metabolites in C. infortunatum using LC-QTOF-MS/MS and investigate its potential in protecting against cognitive decline in rats with scopolamine-induced AD disease. Metabolite profiling was performed on the methanol extract of the plant's aerial parts using LC-QTOF-MS/MS. The inhibitory activity of the acetylcholinesterase enzyme was measured in vitro. To evaluate the cognitive effects, the methanol extract was orally administered at three doses (100, 200, and 400 mg/kg) to scopolamine-induced AD rats, and their cognitive functions were assessed using the novel object recognition test. Additionally, acetylcholinesterase enzyme activity, as well as the levels of acetylcholine, dopamine, noradrenaline, glutathione, malondialdehyde, tumor necrosis factor-α, interleukin-1β, and amyloid-β in the rat hippocampus, were measured using ELISA, followed by histopathological evaluation. A total of 79 metabolites, spanning various chemical classes, such as organic acids, phenolic acids, phenylpropanoids and phenylethanoids, flavonoids, coumarins, other phenolics, and fatty acids and their derivatives, were identified. The results showed that the extract promoted enhanced cognitive functions in the novel object recognition test. Scopolamine administration significantly altered the acetylcholinesterase enzyme activity and biomarker levels in the rat's hippocampus. However, treatment with C. infortunatum at 200 and 400 mg/kg almost restored these neurotransmitter levels to normal, which was further confirmed by histopathological analysis. This study demonstrates the therapeutic potential of C. infortunatum in mitigating cognitive decline in AD, with its first metabolite profiling revealing a range of bioactive compounds. The extract improved cognitive function in scopolamine-induced AD rats, restored acetylcholinesterase activity, normalized neurotransmitter levels, and reduced oxidative stress and inflammation. These findings suggest that C. infortunatum is a promising candidate for the development of natural therapies targeting AD.
阿尔茨海默病（AD）是一项全球性的健康挑战，需要创新方法来进行有效治疗。臭牡丹（马鞭草科）是一种灌木，传统上用作药用植物，用于治疗炎症、皮肤病和支气管炎。本研究旨在使用液相色谱-四极杆飞行时间串联质谱（LC-QTOF-MS/MS）鉴定臭牡丹中的主要生物活性代谢物，并研究其对东莨菪碱诱导的AD病大鼠认知功能下降的保护潜力。使用LC-QTOF-MS/MS对该植物地上部分的甲醇提取物进行代谢物谱分析。在体外测定乙酰胆碱酯酶的抑制活性。为了评估认知效果，将甲醇提取物以三种剂量（100、200和400mg/kg）口服给予东莨菪碱诱导的AD大鼠，并使用新颖物体识别试验评估它们的认知功能。此外，使用酶联免疫吸附测定（ELISA）测量大鼠海马体中的乙酰胆碱酯酶活性以及乙酰胆碱、多巴胺、去甲肾上腺素、谷胱甘肽、丙二醛、肿瘤坏死因子-α、白细胞介素-1β和淀粉样蛋白-β的水平，随后进行组织病理学评估。共鉴定出79种代谢物，涵盖各种化学类别，如有机酸、酚酸、苯丙素类和苯乙醇类、黄酮类、香豆素类、其他酚类以及脂肪酸及其衍生物。结果表明，该提取物在新颖物体识别试验中促进了认知功能的增强。给予东莨菪碱显著改变了大鼠海马体中的乙酰胆碱酯酶活性和生物标志物水平。然而，用200和400mg/kg的臭牡丹进行治疗几乎使这些神经递质水平恢复正常，组织病理学分析进一步证实了这一点。本研究证明了臭牡丹在减轻AD认知功能下降方面的治疗潜力，其首次代谢物谱分析揭示了一系列生物活性化合物。该提取物改善了东莨菪碱诱导的AD大鼠的认知功能，恢复了乙酰胆碱酯酶活性，使神经递质水平正常化，并减轻了氧化应激和炎症。这些发现表明，臭牡丹是开发针对AD的天然疗法的有希望的候选物。
