Quercetin protects against neuronal toxicity by activating the PI3K/Akt/GSK-3β pathway in vivo models of MPTP-induced Parkinson's disease.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-03-27 DOI:10.1007/s10787-025-01712-2

Yajuan Li, Minghao Man, Yiyuan Tian, Gang Zhao, FengZhou Liu, JingYu Zhao, Songya Huang, Junhui Xue, Wei Chang

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引用次数: 0

Abstract

Background: Quercetin is a flavonoid commonly found in various fruits, vegetables, and grains. Studies have demonstrated that quercetin may help protect neuronal cells from damage caused by neurotoxins associated with Parkinson's disease, however, the underlying mechanism remains unclear.

Aim: The current study aimed to investigate the neuroprotective effects of quercetin in MPTP-induced Parkinson's disease mouse models and elucidate its mechanistic role in modulating the PI3K/Akt/GSK-3β signaling pathway.

Materials and methods: Male C57BL/6 mice were divided into control, MPTP, quercetin, and MPTP + quercetin groups. The protective effects of quercetin on Parkinson's disease in mice were evaluated using animal behaviour analysis, histopathological examination, and immunofluorescence staining. Subsequently, network pharmacology was utilized to determine the primary target sites of quercetin in Parkinson's disease. Finally, western blotting and molecular docking techniques were applied to validate the identified targets.

Results: Quercetin significantly improved motor deficits in MPTP mice, reduced neuronal atrophy, and preserved TH⁺ dopaminergic neurons. Western blotting analysis revealed quercetin upregulated anti-inflammatory IL-10 (p < 0.01) and TGF-β (p < 0.01) while suppressing pro-inflammatory IL-1β (p < 0.01) and iNOS (p < 0.01). It activated the PI3K/Akt/GSK-3β pathway by increasing phosphorylation of PI3K (p < 0.01), Akt (p < 0.01), and GSK-3β (p < 0.01). Quercetin also elevated anti-apoptotic Bcl-2 (p < 0.01) and reduced pro-apoptotic Bax (p < 0.01) and Caspase-9 (p < 0.01). Molecular docking confirmed strong binding between quercetin and PI3K/Akt/GSK-3β (binding energies: -6.44 to -5.24 kcal/mol).

Conclusion: Quercetin alleviates Parkinson's disease pathology by inhibiting neuroinflammation, reducing apoptosis, and activating the PI3K/Akt/GSK-3β pathway. These findings underscore its potential as a multi-target therapeutic agent for Parkinson's disease.

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槲皮素通过激活mptp诱导的帕金森病体内模型中的PI3K/Akt/GSK-3β通路来保护神经元毒性。

背景：槲皮素是一种类黄酮，常见于各种水果、蔬菜和谷物中。研究表明，槲皮素可能有助于保护神经细胞免受与帕金森病相关的神经毒素引起的损伤，然而，其潜在机制尚不清楚。目的：本研究旨在探讨槲皮素在mptp诱导的帕金森病小鼠模型中的神经保护作用，并阐明其在调节PI3K/Akt/GSK-3β信号通路中的作用机制。材料与方法：将雄性C57BL/6小鼠分为对照组、MPTP组、槲皮素组和MPTP +槲皮素组。采用动物行为学分析、组织病理学检查和免疫荧光染色评价槲皮素对小鼠帕金森病的保护作用。随后，利用网络药理学确定槲皮素在帕金森病中的主要靶点。最后，应用western blotting和分子对接技术对鉴定的靶点进行验证。结果：槲皮素可显著改善MPTP小鼠的运动缺陷，减轻神经元萎缩，保存TH+多巴胺能神经元。结论：槲皮素可通过抑制神经炎症、减少细胞凋亡、激活PI3K/Akt/GSK-3β通路来缓解帕金森病的病理变化。这些发现强调了其作为帕金森病多靶点治疗剂的潜力。

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

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]