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原人参二醇消除帕金森病模型小鼠的行为障碍和线粒体功能障碍。

Protopanaxadiols Eliminate Behavioral Impairments and Mitochondrial Dysfunction in Parkinson's Disease Mice Model.

机构信息

School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, People's Republic of China.

College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, People's Republic of China.

出版信息

Neurochem Res. 2024 Jul;49(7):1751-1761. doi: 10.1007/s11064-024-04132-w. Epub 2024 Mar 29.

Abstract

Currently, there are no effective therapies to cure Parkinson's disease (PD), which is the second most common neurodegenerative disease primarily characterized by motor dysfunction and degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Protopanaxadiols (PPDs), including 20 (R)- protopanaxadiol (R-PPD) and 20 (S)- protopanaxadiol (S-PPD), are main metabolites of ginsenosides. The role of ginsenosides in neurodegenerative diseases has been thoroughly studied, however, it is unknown whether PPDs can attenuate behavioral deficits and dopaminergic neuron injury in PD model mice to date. Here, we administered PPDs to MPTP-induced PD model mice and monitored the effects on behavior and dopaminergic neurons to investigate the effects of R-PPD and S-PPD against PD. Our results showed that R-PPD and S-PPD (at a dose of 20 mg/kg, i.g.) treatment alleviated MPTP (30 mg/kg, i.p.) induced behavioral deficits. Besides, R-PPD and S-PPD protected MPP-induced neuron injury and mitochondrial dysfunction, and reduced the abnormal expression of Cyt C, Bax, caspase-3 and Bcl-2. These findings demonstrate that R-PPD and S-PPD were potentially useful to ameliorate PD.

摘要

目前,尚无有效的方法可以治愈帕金森病(PD),PD 是第二大常见的神经退行性疾病,主要特征是运动功能障碍和黑质致密部(SNc)中的多巴胺能神经元退化。原人参二醇(PPD)包括 20(R)-原人参二醇(R-PPD)和 20(S)-原人参二醇(S-PPD),是人参皂苷的主要代谢物。人参皂苷在神经退行性疾病中的作用已经得到了深入研究,但是,到目前为止,还不清楚 PPD 是否可以减轻 PD 模型小鼠的行为缺陷和多巴胺能神经元损伤。在这里,我们给 MPTP 诱导的 PD 模型小鼠施用 PPD,并监测其对行为和多巴胺能神经元的影响,以研究 R-PPD 和 S-PPD 对 PD 的作用。我们的结果表明,R-PPD 和 S-PPD(剂量为 20mg/kg,ig)治疗可减轻 MPTP(30mg/kg,ip)诱导的行为缺陷。此外,R-PPD 和 S-PPD 可保护 MPP 诱导的神经元损伤和线粒体功能障碍,并降低 Cyt C、Bax、caspase-3 和 Bcl-2 的异常表达。这些发现表明,R-PPD 和 S-PPD 可能有助于改善 PD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dc0/11144128/96d63089f515/11064_2024_4132_Fig1_HTML.jpg

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