Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.

Abhitinder Kumar, Mohit Agrawal, Yogesh Murti, Simran Behl, Shivendra Kumar, Hema Chaudhary, Kuldeep Singh, Sunam Saha, Sameer Rastogi
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Abstract

Objective: The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus.

Materials and methods: Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue.

Results: The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions.

Conclusion: These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.

保护神经元完整性:揭示NFκB在穿心莲内酯对抗氯化铝诱导的大鼠神经毒性及相关空间记忆损伤的神经保护作用中的可能作用
研究目的本研究旨在评估穿心莲内酯在氯化铝(AlCl3)诱导的神经毒性中的神经保护特性,以及其同时对 Wistar 大鼠空间记忆损伤的影响。本研究阐明了穿心莲内酯治疗大鼠的生化和神经行为结果,强调了与记忆相关的大脑区域,即大脑皮层和海马体:连续 10 天腹腔注射 AlCl3(7 毫克/千克)可显著提高氧化应激标记物的值,同时降低脑内抗氧化酶的浓度。选择穿心莲内酯的剂量(1、2 和 3 毫克/千克)是基于先例的安全性和毒性调查,随后口服给药。通过径向八臂迷宫(RAM)测试对行为参数,特别是空间记忆进行了评估。实验结束当天,评估包括生化参数分析和脑组织的组织学检查:结果:在口服氯化铝的同时口服 1、2 和 3 毫克/千克穿心莲内酯可有效缓解铝暴露引起的行为障碍。值得注意的是,穿心莲内酯能显著抑制大鼠体内的 NFκB。此外,对大鼠大脑皮层和海马的组织病理学检查也提供了佐证,表明穿心莲内酯大大减轻了 AlCl3 的毒性影响,从而保持了这些区域典型的组织结构排列:这些研究结果共同表明,穿心莲内酯有可能通过调节 NFκB 活性和改善 AlCl3 暴露的不良后果来对抗铝毒性引起的记忆损伤。
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