Andrographolide and its sulfated metabolite alleviated DSS-induced inflammatory bowel disease through regulating inflammation and immune via MAPK/NLRP3 pathways and the balance of Th17/Treg cells

Inflammatory Bowel Disease (IBD), is a chronic illness characterized by severe abdominal pain, diarrhea, and weight loss, seriously diminishing patients' quality of life. Andrographolide (AND), a natural diterpenoid from Andrographis paniculata, and its sulfated metabolite, andrographolide sodium bisulfite (ASB), have showed potential anti-inflammatory effects. However, their mechanism in IBD remains elusive. This study investigated the impact of AND and its sulfated derivative ASB, on inflammatory responses in IBD. Our findings revealed that AND and ASB significantly reduced disease activity index (DAI) scores and enhanced intestinal barrier function in dextran sodium sulfate (DSS)-induced mice, thereby ameliorating the course of IBD. Furthermore, AND and ASB inhibited both the mitogen-activated protein kinase (MAPK) and NLRP3 pathways to reduce the release of inflammatory cytokines IL-6 and TNF-α. This mechanism was accompanied by a restoration of immune balance through the modulation of T-helper 17 (Th17) and regulatory T (Treg) cells. The ability of AND and ASB to mitigate chronic inflammation and maintain immune equilibrium presented a promising therapeutic approach for IBD management. These findings suggested that AND and ASB might provide novel therapeutic approaches for IBD, thereby warranting further investigation into their clinical efficacy for disease treatment and maintenance of remission.