Neuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese-induced Parkinson's disease in a rat model: Involvement of multiple pathways

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-10-07 DOI:10.1111/cns.70008

Karema Abu-Elfotuh, Ashwaq N. Abbas, Mazin A. A. Najm, Qutaiba A. Qasim, Ahmed M. E. Hamdan, Amany B. Abdelrehim, Ayah M. H. Gowifel, Aya H. Al-Najjar, Ahmed M. Atwa, Magy R. Kozman, Azza S. Khalil, Amira M. Negm, Sara Nagdy Mahmoud Mousa, Amira M. Hamdan, Rana H. Abd El-Rhman, Shaimaa R. Abdelmohsen, Amina M. A. Tolba, Heba Abdelnaser Aboelsoud, Ahmad Salahuddin, Alshaymaa Darwish

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Abstract

Background

Manganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl₂) in the brain.

Objectives

To explore the neuroprotective effects of natural compounds, namely, micronized zeolite clinoptilolite (ZC) and punicalagin (PUN), either individually or in combination, against MnCl₂-induced Parkinson's disease (PD).

Methods

Fifty male albino rats were divided into 5 groups (Gps). Gp I was used as the control group, and the remaining animals received MnCl₂ (Gp II–Gp V). Rats in Gps III and IV were treated with ZC and PUN, respectively. Gp V received both ZC and PUN as previously reported for the solo-treated plants.

Results

ZC and/or PUN reversed the depletion of monoamines in the brain and decreased acetyl choline esterase activity, which primarily adjusted the animals' behavior and motor coordination. ZC and PUN restored the balance between glutamate/γ-amino butyric acid content and markedly improved the brain levels of brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and decreased glycogen synthase kinase-3 beta activity. ZC and PUN also inhibited inflammatory and oxidative markers, including nuclear factor kappa-light-chain-enhancer of activated B cells, Toll-like receptor 4, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 and caspase-1. Bcl-2-associated X-protein and B-cell leukemia/lymphoma 2 protein (Bcl-2) can significantly modify caspase-3 expression. ZC and/or PUN ameliorated PD in rats by decreasing the levels of endoplasmic reticulum (ER) stress markers (p-protein kinase-like ER kinase (PERK), glucose-regulated protein 78, and C/EBP homologous protein (CHOP)) and enhancing the levels of an autophagy marker (Beclin-1).

Discussion and Conclusion

ZC and/or PUN mitigated the progression of PD through their potential neurotrophic, neurogenic, anti-inflammatory, antioxidant, and anti-apoptotic activities and by controlling ER stress through modulation of the PERK/CHOP/Bcl-2 pathway.

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潘尼卡林和/或微粉沸石clinoptilolite对锰诱导的帕金森病大鼠模型的神经保护作用：多种途径的参与

背景：锰中毒是一种中枢神经系统功能障碍，与帕金森氏症等神经系统缺陷有关，是由氯化锰（MnCl2）在大脑中大量聚集引起的：探索天然化合物（即微粉沸石clinoptilolite（ZC）和punicalagin（PUN））单独或联合对氯化锰诱导的帕金森病（PD）的神经保护作用：将 50 只雄性白化大鼠分为 5 组（Gps）。方法：将 50 只雄性白化大鼠分为 5 组（Gps），Gp I 组为对照组，其余动物接受氯化锰治疗（Gp II-Gp V）。Gps III 和 IV 组大鼠分别接受 ZC 和 PUN 治疗。Gp V 同时接受 ZC 和 PUN 处理，如之前报告的单独处理植物：结果：ZC 和/或 PUN 逆转了大脑中单胺类物质的消耗，降低了乙酰胆碱酯酶的活性，这主要调整了动物的行为和运动协调性。ZC 和 PUN 恢复了谷氨酸/γ-氨基丁酸含量之间的平衡，明显改善了脑源性神经营养因子和核因子红细胞 2 相关因子 2/血红素加氧酶 1 的水平，降低了糖原合酶激酶-3 beta 的活性。ZC 和 PUN 还能抑制炎症和氧化标记物，包括活化 B 细胞的核因子卡巴轻链增强因子、Toll 样受体 4、核苷酸结合域、富含亮氨酸的家族、含 pyrin 结构域的-3 和 caspase-1。Bcl-2相关X蛋白和B细胞白血病/淋巴瘤2蛋白（Bcl-2）可显著改变caspase-3的表达。ZC和/或PUN通过降低内质网（ER）应激标记物（p-蛋白激酶样ER激酶（PERK）、葡萄糖调节蛋白78和C/EBP同源蛋白（CHOP））的水平和提高自噬标记物（Beclin-1）的水平来改善大鼠的帕金森病：ZC和/或PUN具有潜在的神经营养、神经源、抗炎、抗氧化和抗凋亡活性，并通过调节PERK/CHOP/Bcl-2通路控制ER应激，从而缓解了帕金森病的进展。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.