α-Arbutin Protects Against Parkinson's Disease-Associated Mitochondrial Dysfunction In Vitro and In Vivo.

Abstract

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.

• Authors: Yaqi Ding, Deqin Kong, Tong Zhou, Nai-di Yang, Chenqi Xin, Jiajia Xu, Qi Wang, Hang Zhang, Qiong Wu, Xiaomei Lu, Kahleong Lim, Bo Ma, Chengwu Zhang, Lin Li, Wei Huang
• Journal: Neuromolecular medicine (Neuromolecular Med) Vol. 22 Issue 1 Pg. 56-67 (03 2020) ISSN: 1559-1174 [Electronic] United States
• PMID: 31401719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Drosophila Proteins
• Neuroprotective Agents
• Plant Extracts
• Rotenone
• Adenosine Triphosphate
• Arbutin
• Ubiquitin-Protein Ligases
• Adenylate Kinase
• park protein, Drosophila

Topics

• Adenosine Triphosphate (biosynthesis)
• Adenylate Kinase (metabolism)
• Animals
• Antioxidants (isolation & purification, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Arbutin (isolation & purification, pharmacology, therapeutic use)
• Autophagy (drug effects)
• Cell Line, Tumor
• Drosophila Proteins (deficiency, genetics)
• Drosophila melanogaster (drug effects, genetics)
• Drug Evaluation, Preclinical
• Ericaceae (chemistry)
• Female
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, physiology)
• Neuroblastoma (pathology)
• Neuroprotective Agents (isolation & purification, pharmacology, therapeutic use)
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Parkinson Disease (drug therapy, metabolism)
• Parkinsonian Disorders (drug therapy)
• Phytotherapy
• Plant Extracts (chemistry)
• Rotenone (toxicity)
• Ubiquitin-Protein Ligases (deficiency, genetics)