巴比酮通过改变炎症和氧化应激途径对抗脂多糖诱导的啮齿动物记忆缺陷:体内和分子动力学模拟研究。

Muhammad Shahid Nadeem, Jalaluddin Azam Khan, Fahad A Al-Abbasi, May M Alqurashi, Azizah Salim Bawadood, Sami I Alzarea, Nadeem Sayyed, Gaurav Gupta, Imran Kazmi
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引用次数: 0

摘要

背景:记忆丧失和认知能力下降是各种神经退行性疾病的突出症状,影响日常活动并对卫生保健系统造成重大负担。本研究旨在探讨巴比酮对lps诱导的大鼠记忆障碍的影响,并可能为神经退行性疾病的治疗提供新的治疗方法。方法:选用雄性Wistar大鼠30只,分为5个实验组:ⅰ组给予生理盐水作为对照,ⅱ组给予脂多糖,ⅲ组给予脂多糖和巴比吉龙(10 mg/kg/p.o),ⅳ组给予脂多糖和高剂量巴比吉龙(20 mg/kg/p.o),ⅴ组单独给予巴比吉龙(20 mg/kg/p.o)。行为学测试采用Morris水迷宫和y形迷宫。生化标志物如氧化、促炎、凋亡,以及进一步的分子对接和模拟阐明了巴比酮作用的机制。结果:巴比吉龙在MWM和Ymaze测试中均显著提高了大鼠的学习能力,表明记忆增强,延迟时间缩短。此外,巴比酮显示出对氧化应激和炎症标志物的有益作用,表明其可能保护神经元免受损伤并促进认知功能。基于分子对接,巴比酮对不同的分子间相互作用表现出更强的结合亲和力;其中NF-KB (ISVC)相互作用最强。通过分子动力学模拟研究了Barbigerone与1NME_ Barbigerone、1SVC_Barbigerone和4AQ3 4AQ3_Barbigerone形成的配合物的稳定性和收敛性。结论:巴比酮通过恢复内源性抗氧化和促炎细胞因子,对lps诱导的大鼠记忆缺损具有神经元保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Barbigerone against Lipopolysaccharide-Induced Memory Deficit in Rodents via Alteration of Inflammatory and Oxidative Stress Pathway: In vivo and Molecular Dynamics Simulations Study.

Background: Memory loss and cognitive decline are prominent symptoms of various neurodegenerative diseases, impacting daily activities and posing a significant burden on healthcare systems. The study aimed to explore the effect of barbigerone against LPS-induced memory impairment in rats and may offer novel therapeutics for neurodegenerative diseases.

Methods: A total of 30 male Wistar rats were utilized and subsequently divided into five distinct experimental groups: group I received saline water as a control, group II- received LPS, group III - received LPS, and barbigerone (10 mg/kg/p.o.), group IV- received LPS and a higher dose of barbigerone (20 mg/kg/p.o.), and group V -barbigerone alone (20 mg/kg/p.o.). Behavioural test was performed through the Morris water maze and Y-maze test. Biochemical markers such as oxidative, proinflammatory, apoptotic, and further molecular docking and simulations elucidate the mechanisms of barbigerone effects.

Results: Barbigerone significantly improved the learning capacity of rats in both the MWM and Ymaze tests, indicating enhanced memory and reduced latency times. Furthermore, barbigerone exhibited beneficial effects on oxidative stress and inflammation markers, suggesting its potential to protect against neuronal damage and promote cognitive function. Based on molecular docking, barbigerone showed a greater binding affinity with different intermolecular interactions; among them, NF-KB (ISVC) had the most potent interaction. Molecular dynamics simulations were performed to assess the stability and convergence of complexes formed by Barbigerone with 1NME_ Barbigerone, 1SVC_Barbigerone, and 4AQ3 4AQ3_Barbigerone.

Conclusion: These findings demonstrate that barbigerone possesses neuronal protective effects against LPS-induced memory deficits in rats by restoring endogenous antioxidant and pro-inflammatory cytokines.

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