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Astaxanthin inhibits microglia M1 activation against inflammatory injury triggered by lipopolysaccharide through
Xin Zhou1, Junyu Zhang2, Yuxin Li2
1The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China.
Aims:
Astaxanthin is a natural carotenoid, can readily cross the blood-brain barrier and exerts a powerful neuroprotective effect. In this study, experiments were performed to explore the underlying molecular mechanisms of which Astaxanthin inhibiting the microglia M1 activation.
Main Methods:
BV2 cells and mice were pre-treated with Astaxanthin and treated by Lipopolysaccharide (LPS). The expressions of M1-related factors (pro-inflammatory cytokines and M1 markers) were measured by RT-qPCR and western blot. The target association between miR-31-5p and Numb was explored via luciferase activity assay. MiR-31-5p mimic was transfected into BV2 cells, then the cells were treated with Astaxanthin in combination with LPS. The expression of M1-related factors and Notch pathway-related molecules were measured via RT-qPCR, western blot and immunofluorescence assay.
Key Findings:
Precondition of BV2 cells with Astaxanthin inhibited the expression of M1-related factors triggered by LPS. In addition, Astaxanthin decreased the number of Iba1-positive microglia and downregulated the levels of M1-related factors in hippocampus in LPS-treated mice. Further investigation revealed that Astaxanthin-mediated suppression of M1-related factors levels was reversed by miR-31-5p mimic in BV2 cells stimulated by LPS. Subsequently, we verified that miR-31-5p repressed Numb expression by binding to the 3'-UTR of Numb mRNA. Also, Astaxanthin suppressed the expression of Notch1, Hes1 and Hes5 and improved the expression of Numb in BV2 cells challenged by LPS, but this alteration can be reversed by miR-31-5p mimic.
Significance:
Our study demonstrated that down-regulating miR-31-5p by Astaxanthin could be a potential therapeutic approach to suppress neuroinflammation via regulating microglia M1 activation.
Insights
Astaxanthin inhibits neuroinflammation by down-regulating miR-31-5p, suppressing microglia M1 activation. This natural carotenoid shows potential for treating neuroinflammatory conditions.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Astaxanthin, a natural carotenoid, possesses neuroprotective properties and can cross the blood-brain barrier.
- Microglia M1 activation is a key process in neuroinflammation.
Purpose of the Study:
- To investigate the molecular mechanisms by which Astaxanthin inhibits microglia M1 activation.
- To explore the role of miR-31-5p in Astaxanthin's neuroprotective effects.
Main Methods:
- Experiments were conducted on BV2 cells and mice pre-treated with Astaxanthin and stimulated with Lipopolysaccharide (LPS).
- Gene and protein expression of M1-related factors and Notch pathway molecules were analyzed using RT-qPCR, western blot, and immunofluorescence.
- Luciferase activity assays were used to confirm the target association between miR-31-5p and Numb.
Main Results:
- Astaxanthin inhibited LPS-induced M1-related factor expression in BV2 cells and reduced M1 markers in the hippocampus of LPS-treated mice.
- Astaxanthin's suppression of M1 factors was reversed by miR-31-5p mimic, indicating miR-31-5p's role in the mechanism.
- Astaxanthin downregulated Notch pathway components (Notch1, Hes1, Hes5) and increased Numb expression, effects reversed by miR-31-5p mimic.
Conclusions:
- Astaxanthin suppresses neuroinflammation by down-regulating miR-31-5p, thereby inhibiting microglia M1 activation.
- Targeting miR-31-5p with Astaxanthin presents a potential therapeutic strategy for neuroinflammatory diseases.
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