Gastrodin protects dopaminergic neurons via insulin-like pathway in a Parkinson's disease model

• Published in: BMC neuroscience Vol. 20; no. 1; pp. 31 - 11
• Main Authors: Yan, Jinyuan, Yang, Zhongshan, Zhao, Ninghui, Li, Zhiwei, Cao, Xia
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.06.2019; BioMed Central; BMC
• Subjects: alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Animal genetic engineering; Animals; Animals, Genetically Modified; Asian medicine; Benzyl Alcohols - pharmacology; Caenorhabditis elegans; Caenorhabditis elegans Proteins - physiology; Cardiotonic agents; Care and treatment; Chemotaxis; Chemotaxis - drug effects; DAF-2/DAF-16 pathway; Dopamine; Dopamine neurons; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dose-Response Relationship, Drug; Food; Forkhead Transcription Factors - physiology; Gastrodin; Genetic engineering; Genetically modified animals; Genetics; Glucosides - pharmacology; Insulin; Insulin resistance; Kinases; Molecular modelling; Movement disorders; Nematodes; Nervous system; Neurodegeneration; Neurons; Neuropathology; Neuroprotection; Neuroprotection - physiology; Neuroprotective Agents - pharmacology; Oxidative stress; Oxidopamine; Parkinson disease; Parkinson Disease - metabolism; Parkinson Disease - prevention & control; Parkinson's disease; Phenols (Class of compounds); Proteins; Receptor, Insulin - physiology; Risk factors; Signal transduction; Signal Transduction - drug effects; Synuclein; Traditional Chinese medicine; Transgenic animals; Worms; α-Synuclein; α-Synuclein; DAF-2/DAF-16 pathway; Dopamine neurons; Parkinson’s disease; Gastrodin
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/s12868-019-0512-x

Recently, the use of traditional Chinese medicine (TCM) has become more generally accepted, including by the Food and Drug Administration. To expand the use of TCM worldwide, it is important to study the molecular mechanisms by which TCM and its active ingredients produce effects. Gastrodin is an active ingredient from Gastrodia elata Blume. It is reported that gastrodin has neuroprotective function in Parkinson's disease. But its mechanisms of neuroprotection remain not clear in PD. Here, we build two C. elegans PD model using 6-OHDA and transgenic animal to observe the changes of PD worms treated with or without gastrodin to confirm the function of gastrodin, then utilize mutant worms to investigate DAF-2/DAF-16 signaling pathway, and finally verify the mechanism of gastrodin in PD. Gastrodin attenuates the accumulation of α-synuclein and the injury of dopaminergic neurons, improves chemotaxis behavior in Parkinson's disease models, then recovers chemotaxis behavior by insulin-like pathway. DAF-2/DAF-16 is required for neuroprotective effect of dopamine neuron in PD. Our study demonstrated that gastrodin rescued dopaminergic neurons and reduced accumulation of α-synuclein protein, and the activity of gastrodin against Parkinson's disease depended on the insulin-like DAF-2/DAF-16 signaling pathway. Our findings revealed that this insulin-like pathway mediates neuroprotection of gastrodin in a Parkinson's disease model.