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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.

Irritable bowel syndrome (IBS) is a functional gut disorder with high prevalence. Because of various factors involved in its pathophysiology and disappointing results from conventional IBS medications, the treatment of IBS is challenging and use of complementary and alternative medicines especially herbal therapies is increasing. In this paper, electronic databases including PubMed, Scopus, and Cochrane library were searched to obtain any in vitro, in vivo or human studies evaluating single or compound herbal preparations in the management of IBS. One in vitro, 3 in vivo and 23 human studies were included and systematically reviewed. The majority of studies are about essential oil of Menta piperita as a single preparation and STW 5 as a compound preparation. Some evaluated herbs such as Curcuma xanthorriza and Fumaria officinalis did not demonstrate any benefits in IBS. However, it seems there are many other herbal preparations such as those proposed in traditional medicine of different countries that could be studied and investigated for their efficacy in management of IBS.

The etiology of inflammatory bowel disease (IBD) is not yet known, but many factors such as defects in the immune system, oxidative stress, microbial content in the gastrointestinal tract, nuclear factor (NF)-κB, nitric oxide (NO), cyclooxygenase-2 (Cox-2), and leukotriene B4 (LB4) are thought to play a role in its pathogenesis. In traditional Iranian medicine (TIM), several medicinal plants are thought to be effective for the treatment of IBD. In this study, information on all of these remedies were derived from all available old sources such as documents or notes and books and were added to the information derived from modern medical databases covering all in vitro, in vivo and clinical trials. For some of these plants, only one or two mechanisms of action have been found such as in Cassia fistula, Lepidium sativum, and Bunium persicum. However, for some plants various mechanisms of action are known. For example, Commiphora mukul is effective in IBD due to its immunomodulatory, antioxidant, and antibacterial properties and it decreases NF-κB, NO and Cox-2. Another herb, Plantago ovata, has immunomodulatory, antioxidant, anti-inflammatory and wound healing activities and decreases NO and LB4. Considering the mechanisms of action of these plants, the combination of some of them may be useful because of their many mechanisms of action such as Pistacia lentiscus, Bunium persicum, Solanum nigrum, Plantago ovata, Boswellia, Solanum nigrum, Plantago ovata and Commiphora mukul. For some of the herbal products used in TIM such as oleogum resin from Commiphora myrrha, seeds of Ocimum basilicum, seeds of Linum usitatissimum, gum resin of Dracaena cinnabari, seeds of Plantago major, seeds of Lallementia royleana, and seeds of Allium porrum, there is no or not enough studies to confirm their benefits in IBD. It is suggested that an evaluation of the effects of these plants on different aspects of IBD should be performed.

Peptic ulcer disease is a multifactorial and complex disease involving gastric and duodenal ulcers. Despite medical advances, the management of peptic ulcer and its complications remains a challenge, with high morbidity and death rates for the disease. An accumulating body of evidence suggests that, among a broad reach of natural molecules, dietary polyphenols with multiple biological mechanisms of action play a pivotal part in the management of gastric and duodenal ulcers. The current review confirmed that dietary polyphenols possess protective and therapeutic potential in peptic ulcer mediated by: improving cytoprotection, re-epithelialization, neovascularization, and angiogenesis; up-regulating tissue growth factors and prostaglandins; down-regulating anti-angiogenic factors; enhancing endothelial nitric oxide synthase-derived NO; suppressing oxidative mucosal damage; amplifying antioxidant performance, antacid, and anti-secretory activity; increasing endogenous mucosal defensive agents; and blocking Helicobacter pylori colonization associated gastric morphological changes and gastroduodenal inflammation and ulceration. In addition, anti-inflammatory activity due to down-regulation of proinflammatory cytokines and cellular and intercellular adhesion agents, suppressing leukocyte-endothelium interaction, inhibiting nuclear signaling pathways of inflammatory process, and modulating intracellular transduction and transcription pathways have key roles in the anti-ulcer action of dietary polyphenols. In conclusion, administration of a significant amount of dietary polyphenols in the human diet or as part of dietary supplementation along with conventional treatment can result in perfect security and treatment of peptic ulcer. Further well-designed preclinical and clinical tests are recommended in order to recognize higher levels of evidence for the confirmation of bioefficacy and safety of dietary polyphenols in the management of peptic ulcer.

We aimed to evaluate the efficacy of tricyclic antidepressants (TCAs) as a therapeutic option for irritable bowel syndrome (IBS) through meta-analysis of randomized controlled trials. For the years 1966 until September 2008, PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for double-blind, placebo-controlled trials investigating the efficacy of TCAs in the management of IBS. Seven randomized, placebo-controlled clinical trials met our criteria and were included in the meta-analysis. TCAs used in the treatment arm of these trials included amitriptyline, imipramine, desipramine, doxepin and trimipramine. The pooled relative risk for clinical improvement with TCA therapy was 1.93 (95% CI: 1.44 to 2.6, P < 0.0001). Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15 (95% CI: -53.27 to -35.04, P < 0.0001). It is concluded that low dose TCAs exhibit clinically and statistically significant control of IBS symptoms.