Guchang capsule alleviates inflammatory bowel disease by downregulating lncRNA THRIL and inhibiting the p38 MAPK/NF-κB signaling pathway.

Background

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with limited treatment options. Guchang capsule (GC) has been used in traditional Chinese medicine, but its effects on IBD and the underlying molecular mechanisms remain unclear.

Methods

A dextran sulfate sodium (DSS)-induced colitis model in mice and an H₂O₂-induced Caco-2 cell injury model were established. Network pharmacology, Transwell co-culture, lncRNA THRIL overexpression/knockdown, and pathway intervention approaches were employed to systematically investigate the mechanism of GC in IBD.

Results

GC attenuated colonic inflammation and tissue damage in vivo, suppressed pro-inflammatory cytokines while restoring anti-inflammatory cytokines, and exhibited a dose-dependent protective effect on Caco-2 cells in vitro. Network pharmacology suggested that the p38 MAPK and NF-κB pathways might serve as key candidate pathways of GC. Mechanistically, p38 MAPK appeared to act upstream of NF-κB, and GC showed inhibitory effects on the activation of both pathways. In the intestinal epithelial-macrophage co-culture system, GC tended to restore barrier function and promote M1-to-M2 macrophage polarization. GC downregulated THRIL expression both in vivo and in vitro. THRIL overexpression activated p38 MAPK and NF-κB and partially attenuated the protective effects of GC, while THRIL knockdown partially mimicked the anti-inflammatory action of GC and exhibited a certain synergistic tendency.

Conclusion

GC may alleviate DSS-induced colitis by downregulating THRIL and inhibiting the p38 MAPK and NF-κB pathways, providing a molecular basis for its therapeutic application in inflammatory bowel disease.