Published online Jun 28, 2020. doi: 10.3748/wjg.v26.i24.3365
Peer-review started: February 24, 2020
First decision: April 22, 2020
Revised: May 9, 2020
Accepted: June 4, 2020
Article in press: June 4, 2020
Published online: June 28, 2020
Inflammatory bowel disease (IBD) refers to a group of disorders characterized by chronic inflammation of the gastrointestinal (GI) tract. The elevated levels of nitric oxide (NO) in serum and affected tissues; mainly synthesized by the inducible nitric oxide synthase (iNOS) enzyme; can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation. Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs. Thereby, the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway. Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018. We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factor κB (NF-κB) and JAK/STAT signaling pathways. Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms. A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway (i.e., dexamethasone, pioglitazone, tropisetron) or independent from this pathway (i.e., nicotine, prednisolone, celecoxib, β-adrenoceptor antagonists). Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.
Core tip: The present study aimed to investigate the correlation between the level of nitric oxide (NO), and inflammatory bowel disease (IBD). Collected data showed that elevated NO can induce gastrointestinal tract inflammation. Many natural and synthetic agents are able to decrease NO production through different pathways, thereby, improving inflammation and IBD symptoms. This study also determined the pharmacological effects of these agents in suppression of the NO pathway.