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Erqember减轻氯化铝对小鼠的神经毒性作用:基于神经行为学和计算机模拟方法的植物化学见解

Erqember Mitigates Neurotoxic Effects of Aluminum Chloride in Mice: Phytochemical Insights With Neurobehavioral and In Silico Approaches.

作者信息

Khan Habiba, Javaid Sana, Ashraf Waseem, Siddique Farhan, Bibi Mehvish, Ahmad Tanveer, Gill Muhammad Shoaib Ali, Abrar Asad, Alqahtani Faleh, Imran Imran

机构信息

Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan.

Department of Pharmacy, The Women University, Multan, Pakistan.

出版信息

J Toxicol. 2025 Apr 2;2025:3997995. doi: 10.1155/jt/3997995. eCollection 2025.

DOI:10.1155/jt/3997995
PMID:40207183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11981706/
Abstract

The increasing popularity of herbal preparations has prompted people around the world to incorporate herbal products into their balanced diet, aiming to improve brain health and protect against neurological disorders. Erqember(Erq-Em) possesses a blend of various neuroprotective phytocompounds. The present study aimed to phytochemically analyze this polyherbal product and scientifically validate its neurological benefits. After chemical characterization through UHPLC-MS, in vivo studies involved the supplementation of mice with 10 and 20 mL/kg doses of Erq-Em in an AlCl-induced amnesic mice model followed by behavioral assessment for anxiety and cognition in a battery of behavioral tests. Subsequently, whole brains were dissected for biochemical and histopathological analysis. Further, the study also included in silico studies to understand the interaction of detected phytocompounds with acetylcholinesterase protein. The outcomes revealed that mice treated with Eqr-Em were protected from anxiety-like behavior as they dose-dependently prefer innately frightening central, lightened, and elevated zones in OFT, L/D, and EPM tests. Moreover, the Erq-Em supplementation caused improved spontaneous learning in Y-maze and NOR tests, while their memory in passive avoidance and water maze tests was evident from longer step-through and shorter escape latencies, respectively. The biochemical analysis of brain homogenates showed a reduction in AchE and MDA while elevation in SOD and GPx levels in mice receiving Erq-Em. Moreover, the healthy and intact neuronal counts were markedly high in CA1 and DG regions of Nissl's-stained hippocampi of Erq-Em-treated mice. The compounds detected by UPLC-MS showed favorable BBB permeability and interacted well with acetylcholinesterase protein through in silico studies. Overall, the neurological benefits of Erqember might result from enhanced cholinergic neurotransmission and antioxidative activity of its phytocompounds, which together function as multimodal strategies against AlCl-induced neurotoxicity.

摘要

草药制剂越来越受欢迎,促使世界各地的人们将草药产品纳入其均衡饮食中,旨在改善大脑健康并预防神经疾病。Erqember(Erq-Em)含有多种具有神经保护作用的植物化合物。本研究旨在对这种多草药产品进行植物化学分析,并科学验证其对神经系统的益处。通过超高效液相色谱-质谱联用仪进行化学表征后,体内研究涉及在氯化铝诱导的失忆小鼠模型中,给小鼠补充10和20 mL/kg剂量的Erq-Em,随后在一系列行为测试中对焦虑和认知进行行为评估。随后,解剖整个大脑进行生化和组织病理学分析。此外,该研究还包括计算机模拟研究,以了解检测到的植物化合物与乙酰胆碱酯酶蛋白的相互作用。结果显示,用Eqr-Em处理的小鼠免受焦虑样行为的影响,因为在旷场试验、明暗箱试验和高架十字迷宫试验中,它们剂量依赖性地更喜欢天生令人恐惧的中央、明亮和高架区域。此外,补充Erq-Em可改善Y迷宫试验和新物体识别试验中的自发学习能力,而在被动回避试验和水迷宫试验中的记忆能力分别从更长的穿通潜伏期和更短的逃避潜伏期得以体现。对脑匀浆的生化分析表明,接受Erq-Em的小鼠中乙酰胆碱酯酶和丙二醛减少,而超氧化物歧化酶和谷胱甘肽过氧化物酶水平升高。此外,在Erq-Em处理小鼠的尼氏染色海马体的CA1和DG区域,健康完整的神经元数量明显增多。通过超高效液相色谱-质谱联用仪检测到的化合物显示出良好的血脑屏障通透性,并通过计算机模拟研究与乙酰胆碱酯酶蛋白有良好的相互作用。总体而言,Erqember的神经益处可能源于其植物化合物增强的胆碱能神经传递和抗氧化活性,它们共同作为对抗氯化铝诱导的神经毒性的多模式策略。

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