Phyllolobium chinense Fisch Flavonoids (PCFF) Suppresses the M1 Polarization of LPS-Stimulated RAW264.7 Macrophages by Inhibiting NF-κB/iNOS Signaling Pathway
Phyllolobium chinense Fisch Flavonoids (PCFF) Suppresses the M1 Polarization of LPS-Stimulated RAW264.7 Macrophages by Inhibiting NF-κB/iNOS Signaling Pathway
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DOI：
10.3389/fphar.2020.00864
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发表时间：
2020-06-18
影响因子：
5.6
通讯作者：
Wang, Youhua
中科院分区：
文献类型：
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作者：
Fan, Hua;Wu, Qiong;Wang, Youhua
背景：M1巨噬细胞在炎症反应中起重要作用。本研究通过斑马鱼体内急性炎症模型和体外lps诱导的促炎M1巨噬细胞模型，对毛叶总黄酮（phylloobium chinense fish flavonoids， PCFF）的抗炎作用进行了评价。方法：采用高效液相色谱法对三叶鱼黄酮进行质量控制。通过荧光标记的巨噬细胞和中性粒细胞的迁移以及炎症因子的基因表达来评价PCFF对急性损伤斑马鱼的抗炎作用。此外，通过lps诱导的促炎M1 RAW264.7巨噬细胞中促炎介质的相关基因表达及相关信号通路调控，探讨PCFF的抗炎机制。结果：黄芪总黄酮（PCFF）能显著抑制急性切尾斑马鱼巨噬细胞和中性粒细胞迁移及iNOS基因表达。PCFF显著抑制lps刺激的促炎M1 RAW264.7巨噬细胞NO过量产生和iNOS基因过表达。此外，PCFF能显著降低p65蛋白的产量，但对P38、JNK和ERK1/2蛋白的产量没有影响。结论：黄芪总黄酮（PCFF）对急性损伤斑马鱼的炎症反应和lps刺激的M1 RAW264.7巨噬细胞具有显著的抑制作用。其药理机制可能与调节NO过量产生、抑制NF-kappa B/iNOS信号通路有关。
Background: M1 macrophage plays an important role in inflammatory reaction. In this study, potential anti-inflammatory effect of Phyllolobium chinense Fisch flavonoids (PCFF) was assessed via Zebrafish acute inflammation model in vivo and LPS-induced pro-inflammatory M1 macrophage model in vitro.Methods: The quality control of P. chinense Fisch flavonoids (PCFF) was analyzed by HPLC. Anti-inflammatory effect of PCFF on the acute injured zebrafish was evaluated by the migration of fluorescence labeled macrophages and neutrophils, and the gene expression of inflammatory factors. In addition, the anti-inflammatory mechanism of PCFF was investigated by the related gene expression and related signaling pathway regulation of pro-inflammatory mediators in LPS-induced pro-inflammatory M1 RAW264.7 macrophage.Results: P. chinense Fisch flavonoids (PCFF) markedly suppressed macrophage and neutrophil migration and iNOS gene expression in acute injured zebrafish with tail-cutting. PCFF significantly inhibited NO overproduction and iNOS gene overexpression in LPS-sitimulated pro-inflammatory M1 RAW264.7 macrophages. What's more, PCFF could evidently decrease p65 protein production, but had no effect on the production of P38, JNK and ERK1/2 proteins.Conclusion: P. chinense Fisch flavonoids (PCFF) have a remarkable inhibitory effect on the inflammatory response in acute injured zebrafish and LPS-stimulated M1 RAW264.7 macrophage. The pharmacological mechanism may be related to the regulation of NO overproduction and the inhibition of NF-kappa B/iNOS signaling pathway.