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水榆花楸可保护秀丽隐杆线虫中的多巴胺能神经变性。

Sorbus alnifolia protects dopaminergic neurodegeneration in Caenorhabditis elegans.

作者信息

Cheon Se-Myeong, Jang Insoo, Lee Myon-Hee, Kim Dae Keun, Jeon Hoon, Cha Dong Seok

机构信息

a College of Pharmacy, Woosuk University , Jeonbuk , Republic of Korea.

b Department of Korean Internal Medicine , Woosuk University , Jeonbuk , Republic of Korea.

出版信息

Pharm Biol. 2017 Dec;55(1):481-486. doi: 10.1080/13880209.2016.1251468.

Abstract

CONTEXT

The twigs of Sorbus alnifolia (Sieb. et Zucc.) K. Koch (Rosaceae) have been used to treat neurological disorders as a traditional medicine in Korea. However, there are limited data describing the efficacy of S. alnifolia in Parkinson's disease (PD).

OBJECTIVE

This study was conducted to identify the protective effects of the methanol extracts of S. alnifolia (MESA) on the dopaminergic (DA) neurodegeneration in Caenorhabditis elegans.

MATERIALS AND METHODS

To test the neuroprotective action of MESA, viability assay was performed after 48 h exposure to 1-methyl-4-phenylpyridine (MMP) in PC12 cells and C. elegans (400 μM and 2 mM of MMP, respectively). Fluorescence intensity was quantified using transgenic mutants such as BZ555 (Pdat-1::GFP) and and UA57 (Pdat-1::GFP and Pdat-1::CAT-2) to determine MESA's effects on DA neurodegeneration in C. elegans. Aggregation of α-synuclein was observed using NL5901 strain (unc-54p::α-synuclein::YFP). MESA's protective effects on the DA neuronal functions were examined by food-sensing assay. Lifespan assay was conducted to test the effects of MESA on the longevity.

RESULTS

MESA restored MPP-induced loss of viability in both PC12 cells and C. elegans (85.8% and 54.9%, respectively). In C. elegans, MESA provided protection against chemically and genetically-induced DA neurodegeneration, respectively. Moreover, food-sensing functions were increased 58.4% by MESA in the DA neuron degraded worms. MESA also prolonged the average lifespan by 25.6%. However, MESA failed to alter α-synuclein aggregation.

DISCUSSION AND CONCLUSIONS

These results revealed that MESA protects DA neurodegeneration and recovers diminished DA neuronal functions, thereby can be a valuable candidate for the treatment of PD.

摘要

背景

在韩国,桤叶唐棣(蔷薇科)的嫩枝作为传统药物用于治疗神经系统疾病。然而,关于桤叶唐棣对帕金森病(PD)疗效的描述数据有限。

目的

本研究旨在确定桤叶唐棣甲醇提取物(MESA)对秀丽隐杆线虫多巴胺能(DA)神经变性的保护作用。

材料与方法

为测试MESA的神经保护作用,在PC12细胞和秀丽隐杆线虫中分别暴露于1-甲基-4-苯基吡啶(MMP)48小时后进行活力测定(分别为400μM和2mM的MMP)。使用转基因突变体如BZ555(Pdat-1::GFP)和UA57(Pdat-1::GFP和Pdat-1::CAT-2)对荧光强度进行定量,以确定MESA对秀丽隐杆线虫DA神经变性的影响。使用NL5901菌株(unc-54p::α-突触核蛋白::YFP)观察α-突触核蛋白的聚集。通过食物感知试验检测MESA对DA神经元功能的保护作用。进行寿命试验以测试MESA对寿命的影响。

结果

MESA恢复了MPP诱导的PC12细胞和秀丽隐杆线虫的活力丧失(分别为85.8%和54.9%)。在秀丽隐杆线虫中,MESA分别对化学和基因诱导的DA神经变性提供保护。此外,在DA神经元退化的线虫中,MESA使食物感知功能提高了58.4%。MESA还使平均寿命延长了25.6%。然而,MESA未能改变α-突触核蛋白的聚集。

讨论与结论

这些结果表明,MESA可保护DA神经变性并恢复受损的DA神经元功能,因此可能是治疗PD的有价值候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b95/6130644/2473f77ac20c/IPHB_A_1251468_F0001_B.jpg

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