Published online Apr 7, 2018. doi: 10.3748/wjg.v24.i13.1398
Peer-review started: January 28, 2018
First decision: February 10, 2018
Revised: February 12, 2018
Accepted: March 3, 2018
Article in press: March 3, 2018
Published online: April 7, 2018
To investigate the protective effects of Ampelopsis grossedentata (AMP) on dextran sulfate sodium (DSS)-induced colitis in mice based on systems pharmacology approach.
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 DSS-induced 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.
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-α and RANKL/RANK, a receptor activator of NF-κB 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, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8.
AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways.
Core tip: Ulcerative colitis (UC), as one of the major forms of inflammatory bowel disease, could lead to various intestinal and extra-intestinal manifestations, which brings a huge challenge to the health care system. Given studies have confirmed that the flavonoid bioactive compounds contained in Ampelopsis grossedentata (AMP) possess strong antiinflammatory activity, we examined the potential therapeutic effects of AMP on UC based on systems pharmacology. Results showed that AMP could suppress the inflammation-related signaling pathways in dextran sulfate sodium-induced colitis, indicating protective effects on UC, which might provide an effective natural therapy for the treatment and prevention of UC.