Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis

AIM To investigate the protective effects of Ampelopsis grossedentata (AMP) on dextran sulfate sodium (DSS)induced colitis in mice based on systems pharmacology approach. METHODS Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis (UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSSinduced colitis model in C57BL/ 6 mice (n = 10/group) was constructed and treated with 5-aminosalicylic acid (100 mg/kg/d) and AMP (400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry. RESULTS The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-alpha and RANKL/RANK, a receptor activator of NF-.B signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, I kappa B and NF-kappa B, and inhibited the elevated expression levels of TNF-alpha, IL-1 beta, IL-6 and IL-8. CONCLUSION AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-kappa B-mediated inflammatory signaling pathways.