Transmembrane serine protease 2 and angiotensin-converting enzyme 2 anti-inflammatory receptors for COVID-19/inflammatory bowel diseases treatment

long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019(COVID-19).Currently,the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide.It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment.Generally,viral entry causes a'cytokine storm'that induces excessive generation of proinflammatory cytokines/chemokines including interleukin(IL)-6,IL-2,IL-7,tumor necrosis factor-α,and interferon-γ.Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19.Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular.Data from clinical,in vitro,and in vivo studies were collected in English from PubMed,Google Scholar,Scopus,and the Cochrane library until May 2021.

Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways

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 factorκB(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.

The protective effect of a standardized hydroalcoholic extract of Prosopis farcta (Banks & Sol.) J.F.Macbr. fruit in a rat model for experimental ulcerative colitis

Background:Investigating new therapies for inflammatory bowel disease among natural products has recently been gaining attention.Although Prosopis farcta has repeatedly been mentioned in traditional Persian medicine as a therapeutic option for inflammatory bowel disease,no evidence-based investigations have been conducted on this topic.The aim of this study was to assess the impact of P.farcta on acetic acid-induced colitis in rats.Methods:A hydroalcoholic extract of P.farcta fruits was prepared.Thirty-six adult Wistar rats were divided into six groups,and colitis was induced in five groups,except the sham group,using acetic acid solution.The animals received distinctive daily doses of P.farcta(50,75,and 100 mg/kg/day,p.o.)and dexamethasone(1 mg/kg/day,i.p.)as standard treatment for two progressive days,starting from colitis induction.Microscopic and histopathological examinations were performed on inflamed colonic tissue.Tissue concentrations of interleukin-1βand tumor necrosis factor-αwere assessed using enzyme-linked immunosorbent assay kits.To identify the role of oxidative stress in ulcerative colitis,the levels of malondialdehyde and myeloperoxidase were measured in colon tissues.Results:Treatment with all concentrations of P.farcta attenuated inflammation and ulcers compared with saline treatment in the control group(P<0.01 for 50 mg/kg;P<0.001 for 75 and 100 mg/kg/day).The best suppression of tumor necrosis factor-αand interleukin-1βwas observed at a dose of 100 mg/kg P.farcta(P<0.001).This dose showed the best effect in reducing myeloperoxidase and malondialdehyde in ulcerative colitis-induced rats(P<0.001).Conclusion:P.farcta can be considered a promising candidate for treating ulcerative colitis;thus,it requires further confirmation by clinical trials.

Mammalian target of rapamycin;novel insight for management of inflammatory bowel diseases

Inflammatory bowel diseases(IBDs),with blurred etiology,show a rising trend and are of global concern.Of various factors involved in IBD pathogenesis and development,inflammation has been shown to play a major role.Recognition of the molecular and cellular pathways that induce IBD is an emerging subject to develop targeted therapies.Mammalian target of rapamycin(mTOR)is one the most common receptors of many inflammatory pathways,including that of IBD.To this end,we intend to overview the mTOR inhibitors for their possible efficacy in present and future approaches to treatment of IBD.