Plumbagin as a potential therapeutic agent for scopolamine-induced Alzheimer’s disease: Mechanistic insights into GSK-3β inhibition

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-04-16 DOI:10.1016/j.brainres.2025.149650

Rabiya Ahsan , Mohd Muazzam Khan , Anuradha Mishra , Gazala Noor , Usama Ahmad

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Abstract

Background

The study aimed to evaluate Plumbagin’s neuroprotective potential against scopolamine-induced Alzheimer’s disease, proposing that its effects may involve GSK-3β inhibition, a key factor in tau hyperphosphorylation, to promote neuroprotection in Wistar rats.

Methods

Alzheimer’s was induced in male Wistar rats. After acclimatization, the rats were subjected to daily intraperitoneal treatment with scopolamine (0.7 mg/kg) and oral administration of Plumbagin (10 mg/kg) for 13 days. The cognitive function of treated rats was evaluated using the Morris water maze test, along with assessments of locomotor activity, acetylcholinesterase activity (AChE), protein levels, antioxidant parameters, cytokines and Brain-Derived Neurotrophic Factor (BDNF) and brain histopathology (hippocampus).

Results

The Plumbagin (10 mg/kg, oral) as given orally significantly improved neurobehavioral alterations compared to Alzheimer’s induced group. Scopolamine impaired cognitive function and increased locomotor activity (^#P < 0.05). Treatments improved Morris water maze performance, reducing Escape latency time and increasing Time spent in the target quadrant (*P < 0.05). Biochemically, treatments significantly improved BDNF (*P < 0.05), decreased AChE activity, oxidative stress, reduced Interleukin-6 and Tumor Necrosis Factor Alpha (*P < 0.05) and reversed Scopolamine induced hippocampal neuronal loss (^##P < 0.01). Plumbagin showed significant (*P < 0.05) neuroprotective effects, improving cognitive function, reducing AChE activity, Malondialdehyde, oxidative stress, and neuroinflammatory markers exceeding individual treatments in the scopolamine-induced Alzheimer’s disease model. These improvements suggest a possible mechanism through the inhibition of GSK-3β, which may contribute to the observed neuroprotective effects.

Conclusion

This study suggests that Plumbagin’s neuroprotective effects in scopolamine-induced Alzheimer’s disease may involve GSK-3β inhibition. Plumbagin shows significant therapeutic potential for Alzheimer’s treatment, warranting further investigation of its mechanism.

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白藜芦醇作为东莨菪碱诱导的阿尔茨海默病的潜在治疗药物：GSK-3β抑制的机制见解

本研究旨在评估白桦素对东莨菪碱诱导的阿尔茨海默病的神经保护潜力，提出其作用可能涉及抑制tau过度磷酸化的关键因子GSK-3β，以促进Wistar大鼠的神经保护。方法采用雄性Wistar大鼠诱导老年痴呆。适应后，每天腹腔注射东莨菪碱（0.7 mg/kg）和口服白蜡苷（10 mg/kg），连续13 d。采用Morris水迷宫试验评估治疗大鼠的认知功能，同时评估运动活性、乙酰胆碱酯酶活性（AChE）、蛋白质水平、抗氧化参数、细胞因子、脑源性神经营养因子（BDNF）和脑组织病理学（海马）。结果与阿尔茨海默病诱导组相比，口服白桦素（10 mg/kg，口服）可显著改善神经行为改变。东莨菪碱损害认知功能，增加运动活动(#P <；0.05)。处理提高了Morris水迷宫的表现，减少了逃避潜伏期，增加了在目标象限的停留时间(*P <；0.05)。生物化学方面，处理显著提高BDNF (*P <；0.05)，降低乙酰胆碱酯酶活性、氧化应激、白细胞介素-6和肿瘤坏死因子α (*P <；0.05)和逆转东莨菪碱诱导的海马神经元丢失(##P <；0.01)。白藜芦醇显示显著(*P <；0.05)神经保护作用，改善认知功能，降低乙酰胆碱酯酶活性，丙二醛，氧化应激和神经炎症标志物，在东莨菪碱诱导的阿尔茨海默病模型中超过个体治疗。这些改善提示了一种可能的机制，通过抑制GSK-3β，这可能有助于观察到的神经保护作用。结论白桦素对东莨菪碱诱导的阿尔茨海默病的神经保护作用可能与抑制GSK-3β有关。白丹素在阿尔茨海默病的治疗中显示出显著的治疗潜力，值得进一步研究其机制。

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

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.