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Published on: August 23, 2022
Protosappanin A exerts anti-neuroinflammatory effect by inhibiting JAK2-STAT3 pathway in lipopolysaccharide-induced
Li-Chao Wang1, Li-Xi Liao2, Ming-Bo Zhao2
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Abstract:
Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer's disease and Parkinson's disease. Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders. Protosappanin A (PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L.. In this work, the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored. Results showed that PTA significantly inhibited the production of TNF-α and IL-1β in LPS-activated BV2 microglia. Moreover, the mRNA expressions of IL-6, IL-1β, and MCP-1 were reduced by PTA in a dose-dependent manner. Furthermore, PTA suppressed JAK2/STAT3-dependent inflammation pathway through down-regulating the phosphorylation of JAK2 and STAT3, as well as STAT3 nuclear translocation against LPS treatment. These observations suggested a novel role for PTA in regulating LPS-induced neuroinflammatory injuries.
Insights
Protosappanin A (PTA) reduces neuroinflammation by inhibiting key inflammatory markers and suppressing the JAK2/STAT3 pathway in microglia. This suggests PTA
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Microglial activation drives neuroinflammation in diseases like Alzheimer's and Parkinson's.
- Anti-neuroinflammatory agents offer potential therapeutic benefits.
- Protosappanin A (PTA) is a bioactive compound from Caesalpinia sappan L.
Purpose of the Study:
- To investigate the anti-neuroinflammatory effects of PTA on lipopolysaccharide (LPS)-stimulated BV2 microglia.
- To explore the underlying molecular mechanisms of PTA's action.
Main Methods:
- BV2 cells were stimulated with LPS to induce a neuroinflammatory response.
- The effects of PTA on cytokine production (TNF-α, IL-1β, IL-6, MCP-1) were measured.
- The JAK2/STAT3 signaling pathway activation (phosphorylation and nuclear translocation) was assessed.
Main Results:
- PTA significantly inhibited TNF-α and IL-1β production in LPS-activated BV2 cells.
- PTA dose-dependently reduced mRNA expression of IL-6, IL-1β, and MCP-1.
- PTA suppressed the JAK2/STAT3 pathway by inhibiting JAK2 and STAT3 phosphorylation and STAT3 nuclear translocation.
Conclusions:
- PTA exhibits significant anti-neuroinflammatory properties in microglia.
- PTA acts, in part, by modulating the JAK2/STAT3 signaling pathway.
- PTA represents a potential therapeutic agent for neuroinflammatory disorders.
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