α-Arbutin Protects Against Parkinson’s Disease-Associated Mitochondrial Dysfunction In Vitro and In Vivo
Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of dopaminergic neurons in substantia nigra. The underlying mechanisms of PD pathogenesis have not been fully illustrated and currently PD remains incurable. Accumulating evidences suggest that mitochondrial dysfunction plays pivotal role in the dopaminergic neuronal death. Therefore, discovery of novel and safe agent for rescuing mitochondrial dysfunction would benefit PD treatment. Here we demonstrated for the first time that α-Arbutin (Arb), a natural polyphenol extracted from Ericaceae species, displayed significant protective effect on the rotenone (Rot)-induced mitochondrial dysfunction and apoptosis of human neuroblastoma cell (SH-SY5Y). We further found that the neuroprotective effect of Arb was associated with ameliorating oxidative stress, stabilizing of mitochondrial membrane potential, and enhancing adenosine triphosphate production. To investigate the underlying mechanism, we checked the AMP-activated protein kinase and autophagy pathway and we found that both were involved in the neuroprotection of Arb. Moreover, we explored the protective effect of Arb in drosophila PD model and found that Arb rescued parkin deficiency-induced motor function disability and mitochondrial abnormality of drosophila. Taken together, our study demonstrated that Arb got excellent neuroprotective effect on PD models both in vitro and in vivo and Arb might serve as a potent therapeutic agent for the treatment of PD.
Keywordsα-Arbutin Parkinson’s disease Mitochondria Oxidative stress Autophagy
This study was supported from the National Science Foundation of China (Grant Nos. 81672508, 81773802), and Jiangsu Provincial Foundation for Distinguished Young Scholars (BK20170041), Key University Science Research Project of Jiangsu Province (No. 16KJA180004), Natural Science Foundation of Shaanxi Province (2019JM-016), Fundamental Research Funds for the Central Universities and China-Sweden Joint Mobility Project (51811530018).
Compliance with Ethical Standards
Conflict of interests
The authors declare no conflict of interests.
- Fu, W., Zhuang, W., Zhou, S., & Wang, X. (2015). Plant-derived neuroprotective agents in Parkinson’s disease. American Journal of Translational Research, 7(7), 1189–1202.Google Scholar
- Greene, J. C., Whitworth, A. J., Kuo, I., Andrews, L. A., Feany, M. B., & Pallanck, L. J. (2003). Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proceedings of the National Academy of Sciences of the United States of America, 100(7), 4078–4083.CrossRefGoogle Scholar
- Kavitha, M., Manivasagam, T., Essa, M. M., Tamilselvam, K., Selvakumar, G. P., Karthikeyan, S., et al. (2014). Mangiferin antagonizes rotenone: Induced apoptosis through attenuating mitochondrial dysfunction and oxidative stress in SK-N-SH neuroblastoma cells. Neurochemical Research, 39(4), 668–676.CrossRefGoogle Scholar
- Liu, C. S., Chen, N. H., & Zhang, J. T. (2006). Protection of PC12 cells from hydrogen peroxide-induced cytotoxicity by salvianolic acid B, a new compound isolated from Radix Salviae miltiorrhizae. Phytomedicine, 14(7–8), 492–497.Google Scholar
- Solesio, M., Prime, T., Logan, A., Murphy, M. P., Del Mar Arroyo-Jimenez, M., Jordán, J., et al. (2013). The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson’s disease. Biochimica et Biophysica Acta, 1832(1), 174–182.CrossRefGoogle Scholar
- Zhang, H. A., Gao, M., Zhang, L., Zhao, Y., Shi, L. L., Chen, B. N., et al. (2012). Salvianolic acid A protects human SH-SY5Y neuroblastoma cells against H2O2-induced injury by increasing stress tolerance ability. Biochemical and Biophysical Research Communications, 421(3), 479–483.CrossRefGoogle Scholar