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阿魏酰低聚糖通过激活 ERK/CREB/BDNF/TrkB 信号通路改善 MPTP 诱导的小鼠神经毒性。

Feruloylated oligosaccharides ameliorate MPTP-induced neurotoxicity in mice by activating ERK/CREB/BDNF/TrkB signalling pathway.

机构信息

Department of Physiology, School of Medicine, Jinan University, Guangzhou 510632, China.

Guangzhou Key Laboratory of Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, No. 601, West Huangpu Avenue, Guangzhou 510632, China.

出版信息

Phytomedicine. 2023 Jan;108:154512. doi: 10.1016/j.phymed.2022.154512. Epub 2022 Oct 20.

Abstract

BACKGROUND

Feruloylated oligosaccharides (FOs) are natural esterification products of ferulic acid and oligosaccharides.

STUDY DESIGN

In this study, we examined whether FOs contribute to the ensured survival of nigrostriatal dopamine neurons and inhibition of neuroinflammation in Parkinson's disease (PD).

METHODS

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) was injected intraperitoneally into mice to establish a Parkinson's disease (PD) mouse model. FOs (15 and 30 mg/kg) were orally administered daily to the MPTP-treated mice. The rotarod test, balance beam test, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR), and western blot analyses were performed to examine the neuroprotective effects of FOs on MPTP-treated mice.

RESULTS

Our study indicated that FOs increased the survival of dopamine neurons in the substantia nigra pars compacta (SNc) of the MPTP-treated mice. The neuroprotective effects of FOs were accompanied by inhibited glial activation and reduced inflammatory cytokine production. The mechanistic experiments revealed that the neuroprotective effects of FOs might be mediated through the activation of the ERK/CREB/BDNF/TrkB signalling pathway.

CONCLUSION

This study provides new insights into the mechanism underlying the anti-neuroinflammatory effect of phytochemicals and may facilitate the development of dietary supplements for PD patients. Our results indicate that FOs can be used as potential modulators for the prevention and treatment of PD.

摘要

背景

阿魏酰低聚糖(FOs)是阿魏酸和低聚糖的天然酯化产物。

研究设计

本研究旨在探讨 FOs 是否有助于确保黑质多巴胺神经元的存活和抑制帕金森病(PD)中的神经炎症。

方法

将 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP,30mg/kg)腹腔注射到小鼠中,建立帕金森病(PD)小鼠模型。将 FOs(15 和 30mg/kg)每天口服给予 MPTP 处理的小鼠。通过旋转棒试验、平衡梁试验、免疫荧光、酶联免疫吸附试验(ELISA)、定量聚合酶链反应(qPCR)和 Western blot 分析来检测 FOs 对 MPTP 处理的小鼠的神经保护作用。

结果

我们的研究表明,FOs 增加了 MPTP 处理的小鼠黑质致密部(SNc)中多巴胺神经元的存活。FOs 的神经保护作用伴随着小胶质细胞激活的抑制和炎症细胞因子产生的减少。机制实验表明,FOs 的神经保护作用可能是通过激活 ERK/CREB/BDNF/TrkB 信号通路介导的。

结论

本研究为植物化学物质抗炎作用的机制提供了新的见解,并可能有助于开发 PD 患者的膳食补充剂。我们的结果表明,FOs 可以用作预防和治疗 PD 的潜在调节剂。

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