We collected all the data sets of LPS-induced macrophages in the current GEO database for obtain more realistic analysis results. Analysis of the GEO dataset revealed that LPS induces the DEGs in macrophage inflammatory response. Some of these genes were verified by qRT-PCR at the mRNA level. These DEGs represent the characteristic genes that induce inflammation in LPS, and provide clues for future research on the mechanism of inflammation.On this basis, we want to study the influence of paeonol in this model. The biological processes affected by paeonol were mainly "amacrine cell differentiation" and "plasma membrane." PPI analysis of the DEGs further provided clues to the mechanism of paeonol in diseases. All these studies remind us that the effect of paeonol on inflammation may be related to the cell membrane system.
The inflammation-related genes FPR2, Cd83, and Cfb were affected by paeonol in the macrophage model. The FPR2 receptor is associated with various inflammatory diseases, especially chronic inflammatory diseases. However, the mechanism of FPR2 remains unclear. FPR2 activator inhibits cellular inflammatory response by increasing calcium influx. The influxion of Ca2+ can be detected by fluorescence when FPR2 is activated, and this activation is blocked by WRW4 inhibitors. FPR2 ligands can induce calcium influx by activating FPR2, which inhibits inflammation. In this study paeonol could promote calcium influx in FLS cells. However, this trend was blocked by WRW4, a selective inhibitor of FPR2. Therefore, we believe that paeonol may act as a similar FPR2 activator to promote the influx of Ca2+ through direct or indirect effects. In future studies, optimizing the structure of paeonol to find more anti-inflammatory drugs is of significance for the development of subsequent target drugs
In arthritis research, the most important thing is to look at the inflammatory effect of drugs on synovial cells. Consistent with previous research, Paeonol inhibited IL-6, IL‐1β and TNF‐α production and mRNA expression. WRW4 blocked the inhibition of inflammatory cytokines in FLS cells induced by paeonol. This finding suggests that paeonol affects the verification response of FLS cells through FPR2 receptors. Rheumatoid arthritis is characterised by synovial inflammation and proliferation of FLS. We also studied the inhibitory effect of paeonol on the abnormal proliferation of FLS because of the abnormal proliferation of FLS cells in RA disease. Paeonol also inhibited the abnormal proliferation of FLS. However, this inhibitory effect was blocked by WRW4. In conclusion, paeonol can inhibit the inflammatory level of rheumatoid arthritis and the abnormal proliferation of fibroblasts.
There remain insufficiencies in this research. In this study, the way of paeonol activate the downstream signaling pathway has not been detailed. As well, the effect of paeonol on FPR2 has not been extensively studied in experimental animals.