Comprehensive Mechanistic Investigation of Sanren Decoction in Ulcerative Colitis: Enhancement of the Intestinal Barrier, Modulation of Macrophage Polarization, and Regulation of Gut Microbiota

Sanren Decoction (SRD) has emerged as a promising therapeutic agent for ulcerative colitis (UC) due to its multifaceted mechanisms of action. This study employed an integrative methodology, including network pharmacology, molecular docking, and in vivo experimentation, to elucidate the underlying pharmacological mechanisms of SRD in UC management. The findings identified 87 genes targeted by SRD that are associated with UC, highlighting PTGS2 (Prostaglandin-Endoperoxide Synthase 2) as a crucial target involved in inflammatory processes. Molecular docking analysis confirmed significant interactions between the active compounds of SRD and PTGS2, suggesting a potential anti-inflammatory pathway. In vivo experiments utilizing a DSS-induced colitis mouse model demonstrated that SRD effectively ameliorates clinical symptoms and histopathological damage, enhances intestinal barrier integrity, and modulates macrophage polarization from a pro-inflammatory M1 state to an anti-inflammatory M2 phenotype. Furthermore, SRD was found to alter gut microbiota composition by increasing the abundance of beneficial bacteria and influencing metabolic pathways. These findings establish a strong scientific foundation for the potential of SRD as a comprehensive therapeutic approach for UC, offering promising prospects for its integration into clinical practice.