Capsaicin attenuates DSS-induced IBD by suppressing macrophage M1 polarization via inhibition of the TRAF1/NF-κB pathway

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine caused by multiple factors, with a global incidence that is increasing year by year, severely affecting patients' quality of life. Capsaicin (CAP), the main active component in chili peppers, has anti-inflammatory and antioxidant effects. As a key part of the immune system, macrophages play a critical role in maintaining intestinal homeostasis. Growing evidence suggests that M1 macrophage polarization is closely associated with the onset and progression of IBD. This study used a dextran sulfate sodium (DSS)-induced IBD model, lipopolysaccharide (LPS)-induced macrophage M1 polarization and bone marrow-derived macrophages (BMDMs), and found that CAP can significantly alleviate macrophage M1 polarization by reducing the expression of CD86 and iNOS, inhibiting the release of inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and improving intestinal pathological damage. RNA Sequencing (RNA-seq) analysis suggested that CAP may act through the TNF receptor-associated factor 1 (TRAF1)/nuclear factor kappa B (NF-κB) pathway, further, silencing TRAF1 with siRNA and AAV confirmed that this pathway plays a key role in CAP regulation of macrophage polarization and alleviation of IBD. This study reveals the molecular pathway by which CAP alleviates IBD through regulating M1 macrophage polarization, providing an important theoretical basis for a deeper understanding of the pathogenesis of IBD and the development of new therapeutic strategies.