Peptide BG From Bitter Gourd () Improves Adjuvant-Induced Arthritis by Modulating the Necroptosis/Neutrophil Extracellular Traps/Inflammation Axis and the Gut Microbiota.

BG is a novel bioactive peptide derived from bitter gourd (), known for its anti-inflammatory and immunomodulatory properties. In the present study, our objective is to investigate the functional roles and mechanisms of BG in the context of rheumatoid arthritis (RA). A rat model of adjuvant-induced arthritis (AIA) was established by administering complete Freund's adjuvant (CFA). The viability of BG-mediated AIA was evaluated by assessing changes in rat body weight, joint swelling, ankle joint pathology, inflammation, necroptosis, the formation of neutrophil extracellular traps (NETs), and gut microbiota. The results of the study showed that peptide BG was effective in improving weight loss, joint swelling, serum IgM-rheumatoid factor (IgM-RF) level, and pathological injury of ankle joint in rats with AIA. BG administration resulted in a decrease in erythrocyte sedimentation rate, serum C-reactive protein (CRP), and inflammatory factor (interferon- (IFN-γ), interleukin-1 (IL-1), and tumor necrosis factor- (TNF-)) in AIA rats. Additionally, the administration of CFA resulted in an increase in the protein levels of myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone H3 (CitH3), peptidyl arginine deiminase 4 (PAD4), p-mixed lineage kinase domain-like (p-MLKL), and cleaved caspase 8. However, this increase was found to be inhibited by BG treatment. Furthermore, it has been found that peptide BG possesses the capacity to regulate the species composition structure of the intestinal microbiota, thereby, facilitating the reestablishment of microbial diversity and equilibrium. Peptide BG has demonstrated efficacy in ameliorating AIA through its regulation of the necroptosis/NETs/inflammation axis and the gut microbiota. This finding underscores the potential of BG as a promising therapeutic intervention for RA.