人参皂苷Re在MPTP小鼠中发挥神经保护作用：与肠道微生物群和血清代谢的潜在联系。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-07-26 DOI:10.1016/j.neuropharm.2025.110596

Jie Li , Guijia Zhao , Chunhui Yu , Yi Qu , Xiaorui Shen , Yuting Zhao , Jinnan Zhang , Wenhui Lian , Yu Zhao

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引用次数: 0

摘要

用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）建立雄性C57BL/6小鼠帕金森病（PD）模型，通过该模型研究人参皂苷Re （G-Re）的神经保护作用。虽然G-Re在mptp治疗的小鼠中显示出有益的作用，但其体内活性及其治疗PD潜力的机制尚不清楚。本研究综合运用微生物组学和代谢组学分析，研究了mptp诱导小鼠在G-Re干预后肠道微生物和代谢的变化，旨在阐明G-Re在PD中的作用机制。G-Re可减轻mptp处理小鼠的运动障碍，减轻多巴胺能神经元损失，减少α -突触核蛋白聚集，增强抗氧化防御。值得注意的是，G-Re显著增加了双歧杆菌、梭菌和普雷沃氏菌的相对丰度，同时降低了Akkermansia、Sutterella和Allobaculum的相对丰度，从而有助于恢复肠道微生物群组成。非靶向代谢组学显示，G-Re通过调节花生四烯酸、鞘脂和亚油酸代谢途径以及与不饱和脂肪酸生物合成相关的途径的中断，发挥神经保护作用。相关分析进一步证明了特定肠道微生物与鞘脂代谢途径之间的显著关联。此外，G-Re还抑制鞘脂通路中促凋亡蛋白Bax和caspase-3，同时促进抗凋亡蛋白的活性。总的来说，这些发现为支持G-Re治疗PD的治疗潜力提供了科学和理论基础。

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Ginsenoside Re exerts neuroprotective in MPTP mice: potential links to gut microbiota and serum metabolism

A Parkinson's disease (PD) model was established using male C57BL/6 mice administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), through which the neuroprotective effect of Ginsenoside Re (G-Re) was investigated. Although G-Re has demonstrated beneficial effects in MPTP-treated mice, its in vivo activity and the mechanisms underlying its therapeutic potential in PD remain insufficiently understood. In this study, microbiomics and metabolomics analyses were comprehensively employed to investigate gut microbial and metabolic changes in MPTP-induced mice following G-Re intervention, with the aim of elucidating G-Re's mechanisms of action in PD. G-Re administration was found to alleviate dyskinesia, attenuate dopaminergic neuronal loss, reduce alpha-synuclein aggregation, and enhance antioxidant defenses in MPTP-treated mice. Notably, G-Re significantly increased the relative abundance of Bifidobacterium, Clostridium, and Prevotella while decreasing the relative abundance of Akkermansia, Sutterella, and Allobaculum, thereby contributing to the restoration of gut microbiota composition. Non-targeted metabolomics revealed that G-Re exerted neuroprotective effects by modulating disruptions in the arachidonic acid, sphingolipid, and linoleic acid metabolic pathways, as well as pathways related to the biosynthesis of unsaturated fatty acids. Correlation analyses further demonstrated a significant association between specific gut microbes and the sphingolipid metabolic pathway. In addition, G-Re was found to inhibit pro-apoptotic proteins such as Bax and caspase-3 within the sphingolipid pathway while promoting the activity of anti-apoptotic proteins. Collectively, these findings provide both a scientific and theoretical basis supporting the therapeutic potential of G-Re in the treatment of PD.

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).