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

Table 2 Plant-derived compounds affecting inflammatory bowel disease by modulating nitric oxide pathways

Ref.	Phytochemical	type of animal	Model of IBD	Route of administration	Duration of treatment	Numbers of animals in intervention group and control group	Outcomes
[71]	Naringenin (25, 50, 100 mg/kg per day)	Rat	Acetic acid (AA)	Transrectal	7 d before colitis induction	n = 6	Disease activity index (DAI) ↓, total glutathione sulphadryls (T-GSH) ↑, non-protein sulphadryls ↑, DNA, RNA and total protein content ↑, nitrit oxide (NO) ↓, catalase (CAT) ↑, superoxide dismutase (SOD) ↑, tumor necrosis factor (TNF)-α ↓, interleukin (IL)-1β ↓, IL-6 ↓
[82]	Eupatilin (ethanol extract of aerial parts of Artemisiae herba, EIE) and quercetin-3-β-D-glucuronopyranoside from Rumex aquaticus (EIQ) (EIE, 100 mg/kg & EIQ, 30 mg/kg)	Rat	2,4,6-trinitrobenzene sulfonic acid (TNBS)	Oral	48, 24 and 1 h prior to the TNBS instillation and again 24 h later	n = 6	DAI ↓, myeloperoxidase (MPO) ↓, NO ↓, TNF-α ↓, total glutathione sulphadryls (GSH) ↑, malondialdehyde (MDA) ↓
[74]	Naringin (20, 40, or 80 mg/kg)	Rat	AA	Oral	12 d (8 d before colitis induction and 4 d after)	n = 6	DAI ↓, spleen weight ↓, white blood cell (WBC) ↑, red blood cell (RBC) ↑, hemoglobin (Hb) ↑ & platelet ↑, lactate dehydrogenase (LDH) ↓, alkaline phosphatase (ALP) ↓, SOD ↑, GSH ↑, Colon lipid peroxidation (LPO) ↓, NO ↓, MPO ↓, xanthine oxidase activity ↓, protein carbonyl content ↓, the number of unwinded double strand DNA ↓
[222]	Oligonol (0.5 and 5 mg/kg/d)	Mice	Dextran sulfate sodium (DSS)	Oral	7 d before colitis induction	n = 5	DAI ↓, IkBα phosphorylation & degradation ↓, p65 phosphorylation & nuclear translocation ↓, cyclooxygenase (COX-2) ↓, iNOS ↓, expression of antioxidant enzymes ↑, colon carcinogenesis ↓, the incidence and the multiplicity of colonic adenoma ↓
[223]	Algal meroterpene11hydroxy11Omethylamentadione (1, 10 & 20 mg/ kg)	Mice	DSS	Oral	7 d after colitis induction		DAI ↓, MPO ↓, TNF-α ↓, IL-1β ↓, IL-10 ↓, COX-2 ↓, iNOS ↓
[224]	Fraxinellone	Mice	DSS and lipopolysacchari-de (LPS)	intraperitoneal	9 d	n = 10	DAI ↓, MPO ↓, alkaline phosphatase (ALP) ↓, glutathione ↑, IL-1β ↓, IL-6 ↓, IL-18 ↓, TNF-α ↓, inhibition of cluster of differentiation molecule 11B (CD11B).+ macrophage infiltration, ICAM1 ↓, vascular cell adhesion molecule 1 ↓, iNOS ↓, COX-2 ↓, NO ↓, NF-κB signaling ↓ & NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome ↑
[79]	Isoquercitrin (1 and 10 mg/kg/d)	Rat	DSS	Oral	14 d (DSS induced the second half)	n = 8	Colon shortening ↓, COX-2 ↓, iNOS ↓, tissue healing did not encompass rectum
[225]	Oridonin (5.0 and 7.5 mg/kg)	Mice	TNBS	ntraperitoneal	7 d	n = 3-9	DAI ↓, TNF-α ↓, interferon (INF) ↓, IL-17A ↓, iNOS ↓, COX-2 ↓, in vitro lymphocyte proliferation ↓, NF-κB p65 expression & activity ↓
[68]	Cardamonin (20, 50, and 100 mg/kg)	Mice	DSS	Oral	2 d before DSS treatment & 7 d after	n = 10	NO ↓, TNF-α ↓, IL-6 ↓, toll like receptor (TLR)-4 ↓, myeloid differentiation factor (MDF) 88 ↓, IL-1 receptor-associated kinase-1 ↓, IκBα ↓, IκBK-α/β ↓, mitogen-activated protein kinase (MAPK) ↓, c-Jun NH2-terminal kinase ↓, nuclear translocation of NF-κB p65 ↓

IBD: Inflammatory bowel disease.