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神经坚毅金通过减少α-突触核蛋白积累以及Pink/Pdr-1驱动的线粒体功能障碍,减轻秀丽隐杆线虫帕金森模型中6-羟基多巴胺诱导的多巴胺能神经退行性变。

Neurogrit Gold Attenuates 6-OHDA-Induced Dopaminergic Neurodegeneration in Parkinson's Model of Caenorhabditis elegans by Reducing α-Synuclein Accumulation and Pink/Pdr-1 Driven Mitochondrial Dysfunction.

作者信息

Balkrishna Acharya, Pathak Nishit, Singh Rani, Gohel Vivek, Varshney Yash, Dev Rishabh, Varshney Anurag

机构信息

Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, India.

Department of Allied and Applied Sciences, University of Patanjali, Haridwar, India.

出版信息

CNS Neurosci Ther. 2025 May;31(5):e70401. doi: 10.1111/cns.70401.

Abstract

INTRODUCTION

Parkinson's disease (PD) is a neurodegenerative disorder majorly associated with movement and behavioral disturbances. Pathologically, the loss of dopaminergic (DA) neurons triggered by the deposition of α-synuclein (SNCA) leads to the decrease in dopamine levels affecting motor and cognitive functions of the brain. Current pharmacotherapy for PD only addresses its symptoms but is not able to halt its progression. Traditional medicines are being increasingly used for the treatment of neurodegenerative disorders.

AIM

The present study investigated the effects of Neurogrit Gold (NG), a herbo-mineral prescription medicine, on a Parkinson's model of Caenorhabditis elegans.

METHODS

Chemical characterization of NG was performed on HPLC and GC-MS/MS platforms. Evaluation of NG was done in the neurotoxicant 6-OHDA-induced N2, BZ555, and NL5901 strains of C. elegans.

RESULTS

It was observed that NG treatment did not hamper the lifespan, survival, and progeny development of C. elegans strains. The worms treated with NG were able to resist the deleterious effects of 6-OHDA on survival, progeny development, body bends, and chemotaxis in N2 and DA neuron degeneration in BZ555 worms. In NL5901 worms, NG treatment reduced SNCA aggregation, restored lipid content, as well as improved body bends, chemotaxis, and food uptake. Gene expression studies on 6-OHDA exposed and NG-treated N2 worms suggest that the neuroprotective effects of NG stem from its ability to regulate genes involved in mitochondrial autophagy (pink-1, pdr-1); dopamine synthesis (cat-2); redox (sod-3) and protein folding homeostasis (hsf-1, hsp-12.3).

CONCLUSION

Neurogrit Gold has robust neuroprotective effects, making it a suitable treatment option against etiologies of Parkinson's disease.

摘要

引言

帕金森病(PD)是一种主要与运动和行为障碍相关的神经退行性疾病。在病理上,由α-突触核蛋白(SNCA)沉积引发的多巴胺能(DA)神经元丧失导致多巴胺水平降低,影响大脑的运动和认知功能。目前用于治疗帕金森病的药物仅能缓解症状,无法阻止疾病进展。传统药物越来越多地用于治疗神经退行性疾病。

目的

本研究调查了草本矿物处方药Neurogrit Gold(NG)对秀丽隐杆线虫帕金森病模型的影响。

方法

在高效液相色谱(HPLC)和气相色谱-串联质谱(GC-MS/MS)平台上对NG进行化学表征。在神经毒素6-羟基多巴胺(6-OHDA)诱导的秀丽隐杆线虫N2、BZ555和NL5901菌株中对NG进行评估。

结果

观察到NG处理并未妨碍秀丽隐杆线虫菌株的寿命、存活和子代发育。用NG处理的线虫能够抵抗6-OHDA对N2线虫存活、子代发育、身体弯曲和趋化性的有害影响,以及对BZ555线虫DA神经元变性的影响。在NL5901线虫中,NG处理减少了SNCA聚集,恢复了脂质含量,并改善了身体弯曲、趋化性和食物摄取。对暴露于6-OHDA并经NG处理的N2线虫进行的基因表达研究表明,NG的神经保护作用源于其调节参与线粒体自噬(pink-1、pdr-1)、多巴胺合成(cat-2)、氧化还原(sod-3)和蛋白质折叠稳态(hsf-1、hsp-12.3)相关基因的能力。

结论

Neurogrit Gold具有强大的神经保护作用,使其成为治疗帕金森病病因的合适选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65f2/12059624/4a67a81e4a6a/CNS-31-e70401-g001.jpg

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