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Safflower Yellow regulates microglial polarization and inhibits inflammatory response in LPS-stimulated Bv2 cells
Xing-Wang Yang1, Yan-Hua Li2, Hui Zhang3
1"2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, PR China Institute of Brain Science, Shanxi Datong University, Datong, PR China.
Abstract:
Activated microglia, especially polarized M1 cells, produce pro-inflammatory cytokines and free radicals, thereby contributing directly to neuroinflammation and various brain disorders. Given that excessive or chronic neuroinflammation within the central nervous system (CNS) exacerbates neuronal damage, molecules that modulate neuroinflammation are candidates as neuroprotective agents. In this study, we provide evidence that Safflor yellow (SY), the main active component in the traditional Chinese medicine safflower, modulates inflammatory responses by acting directly on BV2 microglia. LPS stimulated BV2 cells to upregulate expression of TLR4-Myd88 and MAPK-NF-κB signaling pathways and to release IL-1β, IL-6, TNF-α, and COX-2. However, SY treatment inhibited expression of TLR4-Myd88 and p-38/p-JNK-NF-κB, downregulated expression of iNOS, CD16/32, and IL-12, and upregulated CD206 and IL-10. In conclusion, our results demonstrate that SY exerts an anti-inflammatory effect on BV2 microglia, possibly through TLR-4/p-38/p-JNK/NF-κB signaling pathways and the conversion of microglia from inflammatory M1 to an anti-inflammatory M2 phenotype.
Insights
Safflor yellow (SY) reduces neuroinflammation by modulating microglia activity. SY shifts microglia from a pro-inflammatory M1 state to an anti-inflammatory M2 phenotype, offering potential neuroprotection.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia, particularly M1 polarized cells, drive neuroinflammation via pro-inflammatory cytokines and free radicals, worsening brain disorders.
- Chronic neuroinflammation in the central nervous system (CNS) amplifies neuronal damage, highlighting the need for neuroprotective agents that modulate inflammation.
Purpose of the Study:
- To investigate the anti-inflammatory effects of Safflor yellow (SY), a key component of traditional Chinese medicine, on BV2 microglia.
- To elucidate the molecular mechanisms underlying SY's modulation of microglial inflammatory responses.
Main Methods:
- BV2 microglia were stimulated with lipopolysaccharide (LPS) to induce an inflammatory M1 phenotype.
- SY treatment was applied to assess its impact on signaling pathways (TLR4-Myd88, MAPK-NF-κB) and cytokine/marker expression.
- Flow cytometry and gene/protein expression analysis were used to evaluate microglial polarization (M1/M2 markers).
Main Results:
- LPS stimulation upregulated TLR4-Myd88 and MAPK-NF-κB pathways, increasing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and COX-2.
- SY treatment inhibited TLR4-Myd88 and p-38/p-JNK-NF-κB signaling pathways.
- SY downregulated M1 markers (iNOS, CD16/32, IL-12) and upregulated M2 markers (CD206, IL-10), indicating a shift towards an anti-inflammatory phenotype.
Conclusions:
- Safflor yellow (SY) exhibits significant anti-inflammatory effects on BV2 microglia.
- SY likely exerts its neuroprotective effects by inhibiting the TLR-4/p-38/p-JNK/NF-κB signaling pathways.
- SY promotes the conversion of microglia from an inflammatory M1 phenotype to an anti-inflammatory M2 phenotype.
