Lonicerin alleviates the progression of experimental rheumatoid arthritis by downregulating M1 macrophages through the NF-kappa B signaling pathway

The present study aimed to evaluate anti-rheumatoid arthritis (RA) effect of Lonicerin (LON), a safe compound with anti-inflammatory and immunomodulatory properties. Nevertheless, the exact role of LON in RA remains elusive. In this test, the anti-RA effect of LON was evaluated in collagen-induced arthritis (CIA) mouse model. Relevant parameters were measured during the experiment; ankle tissue and serum were collected at the end of the experiment for radiology, histopathology, and inflammation analysis. ELISA, qRT-PCR, immunofluorescence, and western blot were used to explore the effect of LON on the polarization of macrophages and related signal pathways. It was discovered that LON treatment attenuated the disease progression of CIA mice with lower paw swelling, clinical score, mobility, and inflammatory response. LON treatment significantly decreased M1 marker levels in CIA mice and LPS/IFN-gamma-induced RAW264.7 cells, while slightly increasing M2 marker levels in CIA mice and IL-4-induced RAW264.7 cells. Mechanistically, LON attenuated the activation of the NF-kappa B signaling pathway, which contributes to M1 macrophage polarization and inflammasome activation. In addition, LON inhibited NLRP3 inflammasome activation in M1 macrophages, thereby reducing inflammation by inhibiting IL-1 ss and IL-18 release. These results indicated that LON might exert anti-RA effects by regulating the polarization of M1/M2 macrophage, especially by inhibiting macrophage polarization toward M1.

Automated summary

The aim of this study was to evaluate the anti-rheumatoid arthritis (RA) effect of Lonicerin (LON), a safe compound with anti-inflammatory and immunomodulatory properties. LON treatment attenuated the disease progression of CIA mice with lower paw swelling, clinical score, mobility, and inflammatory response. Mechanistically, LON regulated the polarization of M1/M2 macrophages, especially by inhibiting macrophage polarization toward M1, and inhibited NF-kappa B signaling pathway and NLRP3 inflammasome activation.