Wolfberry (Lycium barbarum) glycopeptide attenuates dopaminergic neurons loss by inhibiting lipid peroxidation in Parkinson's disease.

IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL
Xiao-Min Lin, Meng Wang, Xin Xiao, Ya-Li Shi, Ya-Si Zheng, Zi-Han Huang, Ya-Ting Cheng, Rui-Ting Huang, Feng Huang, Kun Li, Jie Sun, Wan-Yang Sun, Hiroshi Kurihara, Yi-Fang Li, Wen-Jun Duan, Rong-Rong He
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引用次数: 0

Abstract

Background: Parkinson's disease (PD) is a common neurodegenerative disorder characterized clinically by motor dysfunction due to gradual loss of dopaminergic neurons in the nigrostriatal system. Currently, medications such as levodopa preparations, offer only temporary symptomatic relief without preventing neuronal loss or halting disease progression. In traditional Chinese medicine (TCM), a particular type of wolfberry or goji berry, the fruit of Lycium barbarum L., has been historically regarded for its neuroprotective properties, potentially offering therapeutic benefits for PD. However, scientific validation of these effects remains limited.

Purpose: This study aims to investigate the neuroprotective effects of wolfberry glycopeptide (WGP) on PD progression in various animal models, and to elucidate the underlying mechanisms responsible for its therapeutic action.

Study design: Diverse canonical animal models, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, 6-hydroxydopamine (6-OHDA)-treated rats, and α-synuclein overexpressed hSNCAA53T mice, were used to evaluate WGP's anti-PD efficacy. Behavioral deficits and pathological damage to dopaminergic neurons were assessed to determine WGP's neuroprotective potential.

Methods: After establishing the animal models and administering WGP treatment, PD-like behaviors were assessed using pole test, rotarod test and gait analysis. Dopaminergic neurons loss in the midbrain and striatum was detected by means of immunohistochemistry, immunofluorescence and Western blot analysis. Inflammatory markers in these brain regions were measured by ELISA.

Results: WGP treatment significantly alleviated motor deficits as well as progressive dopaminergic neurons loss. Mechanistically, WGP exerted its neuroprotective effects by regulating iron homeostasis, specifically through the modulation of key proteins such as TFRC, FTH1, and FPN. This function contributed to reducing the accumulation of lipid peroxidation in nigrostriatal system, thereby mitigating neuroinflammation and neuronal degeneration.

Conclusion: Our findings underscore the innovative potential of WGP as a neuroprotective agent in PD, with a unique mechanism of action targeting iron homeostasis and lipid peroxidation-driven neurodegeneration. This study advances the understanding of TCM's therapeutic contributions to neurodegeneration and positions WGP as a strong candidate for further clinical development in PD treatment.

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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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