Lonicerin alleviates the progression of experimental rheumatoid arthritis by downregulating M1 macrophages through the NF‐κB signaling pathway

Abstract

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‐γ‐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‐κB 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‐1β 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.

Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

“…NLRP3 inflammasome activation is the key molecular event in M1 macrophage polarization releasing pro-inflammatory cytokines. For instance, LPS promoted M1-type macrophage polarization to promote NLRP3 inflammasome formation to release pro-inflammatory cytokines IL-1β and IL-18 . SIRT1 overexpression would decrease endogenous LPS production and inhibit macrophagic NLRP3 inflammasome formation to suppress NF-κB-induced inflammation, which together to alleviate hepatic inflammatory injury and fibrosis .…”

Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis

“…Similar results were obtained in another study using Lonicerin as a therapeutic compound. In vivo and in vitro studies revealed that Lonicerin significantly decreased M1 marker levels by attenuating the activation of the NF-κB signalling pathway, which contributes to M1 macrophage polarization and inflammasome activation ( Yang et al, 2023 ).…”

Lonicerin alleviates ovalbumin-induced asthma of mice <i>via</i> inhibiting enhancer of zeste homolog 2/nuclear factor-kappa B signaling pathway

“…and regulates oxidative stress, and immunity. The progress of 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis, candida albicans-caused arthritis and collagen-induced arthritis was suppressed by lonicerin via reducing inflammatory response [ 15 , 16 , 17 ]. EZH2 and NF-κB were targeted by lonicerin, separately, and then apoptosis and inflammation were reduced [ 18 , 19 ].…”