Network pharmacology and metabolomics reveal Jingfang Granules alleviates DSS-induced colitis via the NF-κB/NLRP3/IL-6/STAT3 pathway.

Abstract

BACKGROUND: Granule (JFG) is derived from the renowned ancient Chinese prescription " Shengsheng Zhongmiaofang". Previous studies have demonstrated that JFG can effectively treat wind-cold colds and inflammation-related allergic dermatitis; however, its efficacy in treating Inflammatory bowel disease (IBD) remains uncertain. PURPOSE: The aim of this study was to investigate the protective role of JFG against IBD and to discuss its potential pharmacological mechanisms both in vitro and in vivo. RESULTS: Our results indicate that JFG effectively treated DSS-induced IBD in mice, alleviating weight loss, restoring colon length, and improving colon integrity. Network pharmacology suggested the protective mechanisms may involve the NF-κB/NLRP3 and IL-6/STAT3 pathways. In a mouse colitis model, DSS-induced co-activation of the NF-κB and NLRP3 inflammasomes provoked proinflammatory cytokine production, which subsequently activated the IL-6/STAT3 pathway, triggering intestinal cell apoptosis and mucosal barrier disruption. Conversely, JFG exhibited a protective role in IBD by inhibiting this process. Additionally, 16S rDNA sequencing suggests that JFG also contributes to the therapeutic management of IBD by modulating gut microbiota. Metabolomics results suggest that the therapeutic effects of JFG may be associated with the flavonoids and coumarin compounds it contains. CONCLUSION: In this study, we demonstrate that JFG suppresses macrophage inflammatory responses, alleviates inflammation-induced intestinal epithelial cell apoptosis, and protects intestinal barrier function, thereby treating colitis. This effect is mediated through the inhibition of the NF-κB/NLRP3/IL-6/STAT3 signaling pathway axis.