Magnoflorine Ameliorates Collagen-Induced Arthritis by Suppressing the Inflammation Response via the NF-κB/MAPK Signaling Pathways

Objective: Magnoflorine (Mag) has been reported to have anxiolytics, anti-cancer, and anti-inflammatory properties. In this study, we aim to investigate the effects of Mag on the rheumatoid arthritis (RA) and explore the underlying mechanism using a collagen-induced arthritis (CIA) mouse model and a lipopolysaccharide (LPS)-stimulated macrophage inflammation model. Methods: The in vivo effects of Mag on CIA were studied by inducing CIA in a mouse model using DBA/1J mice followed by treatment with vehicle, methotrexate (MTX, 1 mg/kg/d), and Mag (5 mg/kg/d, 10 mg/kg/d, and 20 mg/kg/d), and the in vitro effects of Mag on macrophages were examined by stimulation of RAW264.7 cells line and peritoneal macrophages (PMs) by LPS in the presence of different concentrations of Mag. Network pharmacology and molecular docking was then performed to predict the the binding ability between Mag and its targets. Inflammatory mediators were assayed by quantitative real-time PCR and enzyme linked immunosorbent assay (ELISA). Signaling pathway changes were subsequently determined by Western blotting and immunohistochemistry (IHC). Results: In vivo experiments demonstrated that Mag decreased arthritis severity scores, joints destruction, and macrophages infiltration into the synovial tissues of the CIA mice. Network pharmacology analysis revealed that Mag interacted with TNF-alpha, IL-6, IL-1 beta, and MCP-1. Consistent with this, analysis of the serum, synovial tissue of the CIA mice, and the supernatant of the cultured RAW264.7 cells and PMs showed that Mag suppressed the expression of TNF-alpha, IL-6, IL-1 beta, MCP-1, iNOS, and IFN-beta. Furthermore, Mag attenuated the phosphorylation of p65, I kappa B alpha, ERK, JNK, and p38 MAPKs in the synovial tissues of the CIA mice and LPS-stimulated RAW 264.7 cells. Conclusion: Mag may exert anti-arthritic and anti-inflammatory effects by inhibiting the activation of NF-kappa B and MAPK signaling pathways.

Automated summary

This study investigated the effects of Magnoflorine (Mag) on rheumatoid arthritis (RA) and the underlying mechanism using mouse models. The results showed that Mag could reduce arthritis severity, joint destruction, and macrophage infiltration. Further analysis revealed that Mag exerted its anti-arthritic and anti-inflammatory effects by inhibiting the activation of NF-kappa B and MAPK signaling pathways.