Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2020; 26(24): 3365-3400
Published online Jun 28, 2020. doi: 10.3748/wjg.v26.i24.3365
Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways
Aida Kamalian, Masoud Sohrabi Asl, Mahsa Dolatshahi, Khashayar Afshari, Shiva Shamshiri, Nazanin Momeni Roudsari, Saeideh Momtaz, Roja Rahimi, Mohammad Abdollahi, Amir Hossein Abdolghaffari
Aida Kamalian, Masoud Sohrabi Asl, Mahsa Dolatshahi, Khashayar Afshari, Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Mahsa Dolatshahi, Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Shiva Shamshiri, Roja Rahimi, Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Nazanin Momeni Roudsari, Amir Hossein Abdolghaffari, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran 1941933111, Iran
Saeideh Momtaz, Amir Hossein Abdolghaffari, Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran 1417614411, Iran
Saeideh Momtaz, Mohammad Abdollahi, Amir Hossein Abdolghaffari, Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Saeideh Momtaz, Amir Hossein Abdolghaffari, Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran 1417614411, Iran
Amir Hossein Abdolghaffari, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Author contributions: Kamalian A, Sohrabi Asl M and Afshari K were involved in the conceptualization, data collection; Dolatshahi M and Shamshiri SH performed the data collection and resources; Momeni Roudsari N was involved in data collection, figures design; Kamalian A, Sohrabi Asl M, Afshari K, Dolatshahi M, Shamshiri SH, Momeni Roudsari N contributed to writing the original draft; Momtaz S and Abdollahi M were involved in supervision, writing review, editing and final approval of the manuscript; Momtaz S was also involved in validation and table design; Rahimi R was involved in provision of study material, conception and design, and final approval of the manuscript; Abdolghaffari AH was involved in the conceptualization, supervision, writing review, editing and final approval of the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Amir Hossein Abdolghaffari, PhD, Assistant Professor, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, No. 99, Yakhchal, Gholhak, Shariati St., P. O. Box: 19419-33111, Tehran 1417614411, Iran. amirhosein172@hotmail.com
Received: February 24, 2020
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
Processing time: 124 Days and 18.5 Hours
Abstract

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.

Keywords: Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Nitric oxide; Nuclear factor-κB; Natural or synthetic mediators

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.