Abstract
Parkinson’s disease (PD) is a neurodegenerative disease characterized by the pathological loss of nigrostriatal dopaminergic neurons, which causes an insufficient release of dopamine (DA) and then induces motor and nonmotor symptoms. Hyperoside (HYP) is a lignan component with anti-inflammatory, antioxidant, and neuroprotective effects. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active neurotoxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) were used to induce dopaminergic neurodegeneration. The results showed that HYP (100 µg/mL) reduced MPTP-mediated cytotoxicity of SH-SY5Y cells in vitro, and HYP [25 mg/(kg d)] alleviated MPTP-induced motor symptoms in vivo. HYP treatment reduced the contents of nitric oxide (NO), H2O2, and malondialdehyde (MDA), as well as the mitochondrial damage of dopaminergic neurons, both in vitro and in vivo. Meanwhile, HYP treatment elevated the levels of neurotrophic factors such as glial cell line–derived neurotrophic factor, brain-derived neurotrophic factor, and recombinant cerebral dopamine neurotrophic factor in vivo, but not in vitro. Finally, Akt signaling was activated after the administration of HYP in MPP+/MPTP-induced dopaminergic neurodegeneration. However, the blockage of the Akt pathway with Akt inhibitor did not abolish the neuroprotective effect of HYP on DA neurons. These results showed that HYP protected the dopaminergic neurons from the MPP+- and MPTP-induced injuries, which did not rely on the Akt pathway.
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We would like to deeply appreciate all authors who performed all eligible studies which have been included in the present paper.
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This study was supported by the National Natural Science Foundation of China (Nos. 81703978 and 81102552), the Central Government Guided Local Funding Projects for Science and Technology Development (No.YDZX20201400001483), the Outstanding Youth Talents Program of Shanxi Province (No. [2019]35), the Natural Science Foundation of Shanxi Province (No.20210302124293), the Research Project supported by Shanxi Scholarship Council of China (No.2021 − 142), the Key science and technology R&D project of Jinzhong (No. Y213004), the Young Scientist Cultivation Program Project, Shanxi University of Chinese Medicine (No.2021PY-QN-03),and the special fund for Science and Technology Innovation Team of Shanxi University of Chinese Medicine (No.2022TD1013).
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Zhi Chai, Cun-Gen Ma, Bo Zhang, Zhen-Yu Li, and Bao-Guo Xiao provided overall guidance for designing the experiment, model establishment, and manuscript writing. Xing-Jie Xu drafted the manuscript and performed experiments in vitro together with Tao Pan and Hui-Jie Fan. Xu Wang contributed to the animal experiments and manuscript writing. Jie-Zhong Yu and Hai-Fei Zhang contributed to the animal experiments and supervised the data analysis. All authors approved the final version of the manuscript.
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Xu, XJ., Pan, T., Fan, HJ. et al. Neuroprotective effect of hyperoside in MPP+/MPTP -induced dopaminergic neurodegeneration. Metab Brain Dis 38, 1035–1050 (2023). https://doi.org/10.1007/s11011-022-01153-8
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DOI: https://doi.org/10.1007/s11011-022-01153-8