Neuroprotective effects of aegeline against LPS-induced memory dysfunction: involvement of hippocampal cholinergic/proinflammatory cytokines receptor modulation and insilico insight

IF 3.3 3区医学 Q2 NEUROSCIENCES

Neuroscience Pub Date : 2026-02-16 Epub Date: 2025-12-19 DOI:10.1016/j.neuroscience.2025.12.048

Khalid Saad Alharbi , Sattam Khulaif Alenezi , Tariq G Alsahli , Reem ALQahtani , Muhammad Afzal , Imran Kazmi , Nadeem Sayyed

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Abstract

Aims

This study aimed to evaluate the neuroprotective effects of aegeline on lipopolysaccharide (LPS) −induced cognitive dysfunction in rats.

Background

The global rise in neuroinflammatory and cognitive disorders demands safe and effective plant-based neuroprotective agents. LPS is a potent endotoxin that triggers inflammation and tissue damage. Aegeline, a hydroxyamide derived from Aegle marmelos, exhibits anti-inflammatory and antioxidant properties. However, its ability to modulate hippocampal cholinergic and proinflammatory cytokine receptors, as well as to protect against LPS-induced memory impairment, remains unexplored.

Methods

Aegeline was administered at doses of 5 and 10 mg/kg for seven days to Wistar rats. Behavioral tests included the Y-maze and the Morris water maze (MWM). Biochemical analyses measured acetylcholinesterase (AChE), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), and inflammatory cytokines: tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. Furthermore, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and caspase-3 markers were evaluated. Additionally, in silico molecular docking and molecular dynamics simulations (MDS) were conducted.

Results

Aegeline treatment improved performance in the Y-maze and MWM tests. It reduced AChE, proinflammatory cytokine, NF-κB, oxidative stress marker, and caspase-3 levels. Antioxidant enzymes and ChAT levels were increased. In silico, aegeline showed strong binding to protein 7JRA with a binding energy of −9.289 kcal/mol, respectively. MDS confirmed the stable interactions with key therapeutic targets.

Conclusion

Aegeline improved cognition, reduced inflammation and oxidative stress, and enhanced antioxidant and cholinergic activity. Its strong molecular binding supports its potential as a neuroprotective agent against memory impairment.

Abstract Image

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aegeline对lps诱导的记忆功能障碍的神经保护作用：海马胆碱能/促炎细胞因子受体调节和计算机洞察的参与。

目的：本研究旨在探讨乙酰胆碱对脂多糖（LPS）诱导的大鼠认知功能障碍的神经保护作用。背景：全球神经炎症和认知障碍的增加需要安全有效的植物性神经保护剂。脂多糖是一种强效内毒素，会引发炎症和组织损伤。Aegeline是一种从蜜瓜中提取的羟酰胺，具有抗炎和抗氧化的特性。然而，其调节海马胆碱能和促炎细胞因子受体的能力，以及防止脂多糖引起的记忆障碍的能力，仍未被探索。方法：Wistar大鼠按5、10 mg/kg剂量给药7 d。行为测试包括y形迷宫和Morris水迷宫（MWM）。生化分析检测了乙酰胆碱酯酶（AChE）、胆碱乙酰转移酶（ChAT）、丙二醛（MDA）、谷胱甘肽（GSH）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、一氧化氮（NO）和炎症细胞因子：肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和IL-6。进一步检测活化B细胞核因子κB轻链增强子（NF-κB）和caspase-3标记物。此外，还进行了分子对接和分子动力学模拟（MDS）。结果：艾格琳治疗改善了y迷宫和MWM测试的表现。降低乙酰胆碱酯酶、促炎细胞因子、NF-κB、氧化应激标志物、caspase-3水平。抗氧化酶和ChAT水平升高。结果表明，egeline与蛋白7JRA结合较强，结合能为-9.289 kcal/mol。MDS证实了与关键治疗靶点的稳定相互作用。结论：Aegeline能改善认知，减轻炎症和氧化应激，增强抗氧化和胆碱能活性。其强大的分子结合能力支持其作为抗记忆障碍的神经保护剂的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience 医学-神经科学

CiteScore

6.20

自引率

0.00%

发文量

394

审稿时长

52 days

期刊介绍： Neuroscience publishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.