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Safflower yellow inhibits the inflammatory response and regulates microglial polarization in LPS-stimulated bv2 cells

      Background: Safflor Yellow (SY), the main active constituent of the traditional Chinese medicine Safflower, is known as a neuroprotective agent that indirectly attenuates neuroinflammation. Macrophage/microglia have different phenotypic and functional states, M1 is associated with inflammatory responses, while M2 results in anti-inflammatory effects.
      Objective: The purpose of this study is to discover the effect of SY on anti-inflammation and polarization of microglia stimulated with LPS as well as related molecular mechanism.
      Material and methods: BV-2 microglial cell line was treated with LPS and/or SY. Molecular biological technique, flow cytometry, and immunohistochemistry were adopted.
      Results: LPS-stimulated BV2 cells upregulated the expression of TLR4 (p < 0.01), Myd88 (p < 0.01), p-NF-κB (p < 0.05), p-P38 (p < 0.01) and p-JNK (p < 0.001), and the expression of inflammatory cytokines IL-1β (p < 0.05),IL-6 (p < 0.05),TNF-a (p < 0.05),NO (p < 0.01) and COX-2 (p < 0.05), but didn't influence the expression of p-ERK (p > 0.05). After SY stimulation, the expression of TLR4, Myd88, p-NF-κB and p-P38, and inflammatory cytokines declined (p < 0.05). Simultaneously, M1 markers iNOS (p < 0.05), CD16/32 (p < 0.05), IL-12 (p < 0.05) and M2 markers CD206 (p < 0.05), IL-10 (p < 0.05) were elevated after LPS stimulation, but M1 markers significantly declined after SY intervention (p < 0.05), while M2 marker CD206 (p < 0.05) and IL-10 (p < 0.05) were significantly elevated (p < 0.001). SY had no influence on M2 marker Arg-1, but the ratio of iNOS/Arg-1 declined compared with LPS-stimulated group (p < 0.05), indicating SY converted inflammatory M1 BV2 cells toward anti-inflammatory M2 microglia.
      Conclusion: SY exhibited anti-inflammatory effect on BV2 microglia possibly through TLR-4/NF-κB/MAPK signaling pathways and the conversion of M1 to M2 microglia. (Grant: The 2011 Cultivation Project of Shanxi University of Traditional Chinese Medicine, 2011PY-1).