Abstract
Wuzi Yanzong Pill (WYP) was found to play a protective role on nerve cells and neurological diseases, however the molecular mechanism is unclear. To understand the molecular mechanisms that underly the neuroprotective effect of WYP on dopaminergic neurons in Parkinson’s disease (PD). PD mouse model was induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Gait and hanging tests were used to assess motor behavioral function. Immunofluorescence assay was used to determine TH-positive neurons in substantia nigra (SN). Apoptosis, dopamine and neurotrophic factors as well as expression of PI3K/Akt pathway were detected by TUNEL staining, ELISA and western blotting, respectively. First, it was observed that WYP intervention improved abnormal motor function in MPTP-induced PD model, alleviated the loss of TH+ neurons in SN, and increased dopamine content in brain, revealing a potential protective effect. Second, network pharmacology was used to analyze the possible targets and pathways of WYP action in the treatment of PD. A total of 126 active components related to PD were screened in WYP, and the related core targets included ALB, GAPDH, Akt1, TP53, IL6 and TNF. Particularly, the effect of WYP on PD may be medicate through PI3K/Akt signaling pathway and apoptotic regulation. The WYP treated PD mice had higher expression of p-PI3K, p-Akt and Bcl-2 but lower expression of Bax and cleaved caspase-3 than the non-WYP treated PD mice. Secretion of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) were also increased in the treated mice. WYP may inhibit apoptosis and increase the secretion of neurotrophic factor via activating PI3K/ Akt signaling pathway, thus protecting the loss of dopamine neurons in MPTP-induced PD mice.
Highlights
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Network pharmacology approach combined with experimental verification to clarify the mechanism.
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Wuzi Yanzong Pill ameliorated MPTP-induced PD mice by activating PI3K/Akt signaling pathway.
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Wuzi Yanzong Pill inhibited apoptosis of dopaminergic neurons in MPTP-induced PD mice.
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Data are available from the corresponding author upon request.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No.81703978, 81102552), the Central Government Guided Local Funding Projects for Science and Technology Development(No.YDZX20201400001483), Outstanding Youth Talents Program of Shanxi Province(No.〔2019〕35), the Natural Science Foundation of Shanxi Province (No. 201901D111334), the Returned Chinese Scholars Technology Activities Preferred Project, Shanxi Province of China(No. 20200026), the Research Project supported by Shanxi Scholarship Council of China(No.2021-142), Shanxi university Science and technology innovation Project(No.2019L0724), the Key science and technology R&D project of Jinzhong (No.Y213004) , and the Young Scientist Cultivation Program Project, Shanxi University of Chinese Medicine (No.2021PY-QN-03).
Funding
This work was supported by the National Natural Science Foundation of China (No.81703978, 81102552), the Central Government Guided Local Funding Projects for Science and Technology Development(No.YDZX20201400001483), Outstanding Youth Talents Program of Shanxi Province(No.〔2019〕35), the Natural Science Foundation of Shanxi Province (No. 201901D111334), the Returned Chinese Scholars Technology Activities Preferred Project, Shanxi Province of China(No. 20200026), the Research Project supported by Shanxi Scholarship Council of China(No.2021–142), Shanxi university Science and technology innovation Project(No.2019L0724), the Key science and technology R&D project of Jinzhong (No.Y213004), and the Young Scientist Cultivation Program Project, Shanxi University of Chinese Medicine (No.2021PY-QN-03).
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Wei Hang, Hui-jie Fan, Yan-rong Li and Qi Xiao carried out the studies, participated in collecting data, and drafted the manuscript. Zhi Chai, Cun-gen Ma, Bao-guo Xiao and Xiao-ming Jin performed the statistical analysis and participated in its design. Lu Jia, Yao Gao, Jie-zhong Yu and Li-juan Song participated in acquisition, analysis, or interpretation of data. All authors read and approved the final manuscript.
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Hang, W., Fan, Hj., Li, Yr. et al. Wuzi Yanzong pill attenuates MPTP-induced Parkinson’s Disease via PI3K/Akt signaling pathway. Metab Brain Dis 37, 1435–1450 (2022). https://doi.org/10.1007/s11011-022-00993-8
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DOI: https://doi.org/10.1007/s11011-022-00993-8