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Gastrodin Protects Neuronal Cells Against Oxidative Stress Through miRNA-125b-5p/Mamdc2 Axis
Lei Hu1,2, Chao Lin3, Renfu Li4
1National Clinical Research Center for Child Health of Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China.
Abstract:
Deregulated reactive oxygen species (ROS) levels trigger oxidative stress (OS) injury that is closely associated with the pathophysiology of various neurological disorders. Therefore, therapeutic efforts at oxidative events in the pathway of neuronal degeneration would be promisingly helpful for intervention and treatment of related diseases. Here, we report that gastrodin, the main bioactive constituent of Rhizoma Gastrodiae, protects the mouse hippocampal HT22 cells from OS caused by hydrogen peroxide (H2O2), including the increased cell viability, elevated Glutathione (GSH) levels, decreased Malondialdehyde (MDA) activity, and down-regulated ROS levels with restored cell morphology. Through RNA-sequencing (RNA-Seq) and multiple experiments, we screened the gene Mamdc2 that could be a potential regulating target of gastrodin. Mechanistically, gastrodin exerts its protective effects on neuronal cells from oxidative injury by suppressing miRNA-125b-5p, which increases its target Mamdc2 expression. Overexpression of miR-125b-5p mimics significantly attenuates the gastrodin-triggered protective effects against H2O2 in HT22 cells, including the decreased cell viability, down-regulated GSH activity, increased MDA activity, and up-regulated ROS production, compared to the gastrodin-administration with control miRNA group. However, these results could be effectively restored by the ectopic expression of Mamdc2, leading to the opposite outcomes to those of miR-125b-5p mimics-overexpression. Thus, the current study provides evidence that gastrodin has the potential for intervention and therapy of OS injury-associated neurological diseases in future.
Insights
Gastrodin protects neuronal cells from oxidative stress by regulating miRNA-125b-5p and Mamdc2 expression. This finding offers potential therapeutic strategies for neurological disorders linked to oxidative damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Deregulated reactive oxygen species (ROS) cause oxidative stress (OS) and neuronal degeneration, contributing to neurological disorders.
- Therapeutic interventions targeting oxidative events are crucial for treating neurodegenerative diseases.
Purpose of the Study:
- To investigate the neuroprotective effects of gastrodin, a key compound from Rhizoma Gastrodiae, against oxidative stress in mouse hippocampal HT22 cells.
- To elucidate the molecular mechanism underlying gastrodin's protective action, focusing on its interaction with miRNA-125b-5p and Mamdc2.
Main Methods:
- Utilized hydrogen peroxide (H₂O₂) to induce oxidative stress in HT22 cells.
- Assessed cell viability, glutathione (GSH), malondialdehyde (MDA) levels, and ROS production.
- Employed RNA-sequencing (RNA-Seq) to identify potential gastrodin targets.
- Manipulated miRNA-125b-5p and Mamdc2 expression through mimics and ectopic expression to confirm the regulatory pathway.
Main Results:
- Gastrodin treatment significantly enhanced HT22 cell viability, increased GSH, decreased MDA activity, and reduced ROS levels.
- Gastrodin was found to suppress miRNA-125b-5p, leading to increased expression of its target gene, Mamdc2.
- Overexpression of miRNA-125b-5p reversed gastrodin's protective effects, while Mamdc2 restoration counteracted these effects.
Conclusions:
- Gastrodin confers neuroprotection against oxidative stress by inhibiting miRNA-125b-5p and upregulating Mamdc2 expression.
- The gastrodin-miRNA-125b-5p-Mamdc2 axis represents a novel therapeutic target for neurological diseases associated with oxidative stress.
- Gastrodin demonstrates significant potential for the intervention and treatment of oxidative injury-related neurological disorders.
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