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Hyperoside Reduces Rotenone-induced Neuronal Injury by Suppressing Autophagy

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Abstract

Hyperoside has a variety of pharmacological activities, including anti-liver injury, anti-depression, anti-inflammatory, and anti-cancer activities. However, the effect of hyperoside on Parkinson’s disease (PD) is still unclear. Therefore, we tried to study the therapeutic effect and mechanism of hyperoside on PD in vivo and in vitro models. Rotenone was used to induce PD rat model and SH-SY5Y cell injury model, and hyperoside was used for intervention. Immunohistochemistry, animal behavior assays, TUNEL and Western blot were constructed to observe the protective effect and related mechanisms of hyperoside in vivo. Cell counting kit-8 (CCK-8), flow cytometry, Rh123 staining and Western blot were used for in vitro assays. Rapamycin (RAP) pretreatment was used in rescue experiments to verify the relationship between hyperoside and autophagy in rotenone-induced SH-SY5Y cells. Hyperoside promoted the number of tyrosine hydroxylase (TH)-positive cells, improved the behavioral defects of rats, and inhibited cell apoptosis in vivo. Different concentrations of hyperoside had no significant effect on SH-SY5Y cell viability, but dramatically reversed the rotenone-induced decrease in cell viability, increased apoptosis and loss of cell mitochondrial membrane potential in vitro. Additionally, hyperoside reversed the regulation of rotenone on the Beclin1, LC3II, Bax, cleaved caspase 3, Cyc and Bcl-2 expressions in rat SNpc tissues and SH-SY5Y cells, while promoted the regulation of rotenone on the P62 and α-synuclcin. Furthermore, RAP reversed the effect of hyperoside on rotenone-induced SH-SY5Y cells. Hyperoside may play a neuroprotective effect in rotenone-induced PD rat model and SH-SY5Y cell model by affecting autophagy.

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Data Availability

The analysed data sets generated during the study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This work was supported by the National Natural Science Foundation of China (Nos. 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 (No. 2021-142), Shanxi university Science and technology innovation Project (No. 2019L0724), the Young Scientist Cultivation Program Project, Shanxi University of Chinese Medicine (No. 2021PY-QN-03).

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Authors and Affiliations

Authors

Contributions

Substantial contributions to conception and design: HF, YL. Data acquisition, data analysis and interpretation: MS, WX, LS, QW, BZ, JY, XJ, CM, ZC. Drafting the article or critically revising it for important intellectual content: HF, YL, MS, WX, LS, QW, BZ, JY, XJ, CM, ZC. Final approval of the version to be published: HF, YL, MS, WX, LS, QW, BZ, JY, XJ, CM, ZC. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: HF, YL, MS, WX, LS, QW, BZ, JY, XJ, CM, ZC.

Corresponding authors

Correspondence to Cungen Ma or Zhi Chai.

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The authors declare no conflicts of interest.

Ethical Approval

Animal assays were permitted by the Ethical Committee of Experimental Animals of Academic Committee of Shanxi University of Traditional Chinese Medicine (AP202004018), and performed in accordance with the guidelines of the China Council on Animal Care and Use. All rats were bred in a SPF-level animal center under standard laboratory conditions.

Consent to Participate

Hyperoside (PHL89227, ≥ 95.0%) was purchased from Phyproof Company (Germany). Rotenone (R8875, ≥ 95.0%) was purchased from Sigma-Aldrich (USA). Specific pathogen-free (SPF) male Sprague–Dawley (SD) rats (240–260 g) were purchased from Jiangsu Ailingfei Biotechnology Co. LTD (China).

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Fan, H., Li, Y., Sun, M. et al. Hyperoside Reduces Rotenone-induced Neuronal Injury by Suppressing Autophagy. Neurochem Res 46, 3149–3158 (2021). https://doi.org/10.1007/s11064-021-03404-z

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