Table 1.

In vivo and in vitro studies evaluating phytochemicals’ roles as NF-kB regulators on inflammatory bowel diseases.

Phytochemicals	In Vivo/In Vitro Model(s)	Effective Dose(s)/ Concentration(s)	Related Clinical Symptoms of IBD	NF-kB-Related Dysregulation Indicators	Related Molecular Mechanisms in Regulation of NF-kB in IBD	Ref.
Curcumin	DSS-induced FVB/NJ mice model of colitis and NFκB-RE-Luc transgenic mice model of colitis	3 mg/day of TDNPs for 1 week orally	↑Inflammatory cells infiltration in the lamina propria, ↑epithelial erosion, ↑interstitial edema, and ↓colonic goblet cells	↑TNF-α, ↑IL-6, ↑IL-1β, ↑OS-related protein, ↓HO-1, and ↑MPO	↓NF-kB-p65-dependent luciferase activity, ↓phospho-NF-kB-p65 and ↓nuclear translocation of p65	[17]
	TNBS-induced Wistar Hannover rats model of colitis	20 mg/kg/day for 1 week orally	↑Inflammatory cells infiltration and ↑ulcer and granuloma formation	↑IL-6, ↑TNF-α, ↑MPO, ↑MDA, and ↑NO	↓NF-kB-related proteins expression and ↓oxidative-related enzymes expression	[18]
	DSS-induced BALB/c mice model of colitis	100 mg/kg mixed with olive oil in the chow	↓Body weight, ↑DAI, and ↓colon length	↑iNOS, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑nitrite, and ↑S-nitrosylation of IKKβ	↓S-nitrosylation of IKKβ and ↓IκB phosphorylation	[19]
	TNBS-induced Sprague-Dawley rats model of colitis	100 mg/kg/day for 1 week orally	↑DAI score	↑MPO, ↑NF-kB mRNA, ↑IL-27, ↑TLR4 expression, ↑NF-kB-p65, and ↑IL-27 p28	↓NF-kB mRNA and ↓NF-kB-p65	[20]
	TNBS-induced Sprague-Dawley rats model of colitis	100 mg/kg and 200/mg/kg orally 2 h prior to induction of colitis	↓Body weight, ↑bloody diarrhea, thickened colon wall, ↓depletion of goblet cells, ↑hemorrhagic intestinal necrosis, ↑mucosal ulcerations, and ↑inflammatory cells infiltration	↑MPO and ↑NF-kB expression	↓NF-kB-related proteins expression and ↓oxidative-related enzymes expression	[21]
	Bacteria-induced Specific pathogen-free wild-type 129/SvEv mice and germ-free IL 10/mice models of colitis	0.1, 0.5, and 1% curcumin-supplemented diets for 5 days	↑Intestinal-associated ↑crypt hyperplasia, ↑lymphocytic and neutrophilic infiltrations, and ↑mucosal ulceration	↑IL-12/23p40, ↑IFN-γ, ↑NF-kB activation, and ↑pSer276-p65	↓IFN-γ and IL-12/23p40 genetic expression, ↓phospho-p65-positive expression, ↑IL-10 mRNA, ↓NF-kB-related proteins expression	[22]
	DNCB-induced Wistar rats model of colitis	25, 50, and 100 mg/kg/day of curcumin orally for 10 days	↑Intestinal ulcers, ↑inflammation in the colon, and ↓colon length	↑MPO, ↑LPO and ALP activities; ↑iNOS, and ↑NF-kB-related proteins expression	↓NF-kB-related proteins expression and ↓iNOS expression	[23]
	TNBS-induced Sprague–Dawley rats model of colitis	30 mg/kg/day intraperitoneally for 14 days	↑Intestinal epithelial necrosis, ↑glandular destruction, ↑inflammatory cells infiltration, ↓body weight	↑IL-1β mRNA, ↑TNF-α mRNA, ↑IFN-γ mRNA, ↑COX-2 mRNA, ↓PPAR-γ, ↓PGE2, ↑15d-PGJ2, ↓mRNA IL-4	↑mRNA do PPARγ, ↑15d-PGJ2, ↑PPAR-γ, ↓COX-2 mRNA, ↓IL-1β mRNA, ↓TNF-α mRNA, ↓IFN-γ mRNA, and ↑IL-4 mRNA	[24]
	TNBS-induced Wistar rats model of colitis	2% of curcumin mixed with the chow for 14 days	↓Body weight, intestinal ulcers, ↑inflammatory cells infiltration	↑NF-kB DNA ligation activity, ↑IkB degradation, ↑IL-1β and ↓IL-10	↓NF-kB DNA ligation activity, ↓IkB degradation, and ↓IL-1 β mRNA	[25]
	TNBS-induced BALB/c mice model of colitis	0.25% of curcumin mixed with the chow for 10 days	↓Body weight, ↑inflammatory cellular infiltration, and ↑mucosal and muscle damage	↑MPO, ↑IL-1 β, ↑NF-kB DNA ligation activity, and ↑p38 MAPK	↓NF-kB DNA ligation activity and ↓p38 MAPK	[26]
	TNBS-induced C3H mice model of colitis	25–300 mg/kg/day of curcumin orally for 10 days	↑Hemorrhagic and ulcerative damage to the distal colon, ↑mucosal congestion, ↑leucocyte cellular infiltrate in the submucosa, and ↓body weight	↑NO, ↑MPO, ↑MDA, ↑protease activities, ↑IFN-γ and IL-12 p40 mRNAs, and ↑iNOS	↓Serine protease activities, ↓IFN-γ and IL-12 p40 mRNA levels, ↓NF-kB-related proteins expression	[27]
	TNBS-induced C57BL/6 and BALB/c mice models of colitis	0.5%, 2.0%, or 5.0% of curcumin mixed with the chow for 7 days	↓Body weight, ↑crypts distortion, ↓goblet cells, and mononuclear cells infiltration	↑p65 nuclear expression, ↑IkB degradation, ↑macrophage infiltration, ↑IL-18, ↑NF-kB DNA ligation activity, ↑IL-6 mRNA, ↑IFN-γ mRNA, ↑TNF-α mRNA, and ↑IL-12 mRNA	↓IkB degradation, ↓NF-kB DNA ligation activity, ↓IL-6 mRNA, ↓IFN-γ mRNA, ↓TNF-α mRNA, and ↓IL-12 mRNA	[28]
Resveratrol	TNBS-induced C57BL/6 mice model of colitis	10 µL 4.5 mM and 10 µL 45 mM/day intraperitoneally for 4 days	Weight loss, diarrhea, bloody stool, ↑MPO activity, ↑DAI score, ↑colonic cytokine levels, and ↑visceral pain	↑pNF-kB, ↑TNF-α mRNA, ↑TNF-α, ↑TGF-β mRNA, ↑TGF-	↓pNF-Κb, ↓TNF-α mRNA, and ↓TGF-β mRNA	[29]
	LPS-treated Caco-2 cells	10–50 μM during 1 h of incubation	↑Colon inflammation measured by COX-2 and PGE2 expression levels	↑p65 nuclear translocation, ↑COX-2, ↑PGE2	↓p65 nuclear translocation, ↓IKK phosphorylation, ↓COX-2 mRNA, and ↓IkBα phosphorylation and degradation	[30]
	DSS-induced C57BL/6 mice model of colitis	100 µL of 10, 50, and 100 mg/kg on alternate days orally for 7 days	Colon inflammation (lymphocyte infiltration and distortion of glands), weight loss, and ↑serum pro-inflammatory cytokines	↑IL-6, ↑IL-1β, ↑IFN-γ, ↑TNF-α, ↑p-IkBα, ↓SIRT1	↓p-IkBα and ↑SIRT1	[31]
	DSS-induced ICR mice model of colitis	10 mg/kg/day orally for 7 days	↑Histopathological score	↑NF-kB-DNA binding complex, ↑IKKβ catalytic activity, ↑ERK phosphorylation, ↑iNOS expression, ↑STAT3	↓ERK phosphorylation, ↓NF-kB-DNA binding complex, and ↓IKKβ catalytic activity	[32]
	TNBS-induced Wistar mice model of colitis	10 mg/kg/day orally for 14 days	↑Macroscopic inflammation, presence of adhesions between the colon and small bowel and other organs, ulcers, crypt distortion, ↑leukocyte involvement, ↑pro-inflammatory cytokines production, and weight loss	↑MPO, ↑TNF-α, ↑NF-kB p65, ↑COX-2, ↑PGD2	↑Inflammatory mucosa cells apoptosis and ↓NF-kB p65	[33]
3-(4-Hydroxyphenyl)-propionic acid	DSS-induced colitis in antibiotics-treated pseudo-germ-free mice and LPS-stimulated RAW264.7 cells	-	↑Intestinal inflammation and ↑OS both in vivo and in vitro	↑NF-kB-related activation proteins and ↑MAPK	↓NF-kB-related activation proteins and ↓MAPK	[34]
Sesamol	DSS-induced C57BL/6 mice model of colitis	100 mg/kg/day orally for 6 weeks	↑DAI, histopathological changes, and ↓intestinal barrier integrity	↑COX-2, ↑iNOS, ↑IL-6, ↑IL-1β, ↑TNF-α, ↑TLR4	↓COX-2 mRNA, ↓iNOS mRNA, ↓IL-6 mRNA, ↓IL-1β mRNA, ↓TNF-α mRNA, ↓TLR4 mRNA, and ↑p-NF-kB/NF-kB ratio	[35]
Kaempferol	DSS-induced C57BL/6 mice model of colitis	50 mg/kg/day orally for 14 days	↑DAI, ↓colon length, ↑intestinal mucosal injury, and altered gut microbiota	↑IL-6, ↑IL-1β, ↑TNF-α, ↑IL-1β mRNA, ↑IL-6 mRNA, ↑TNF-a mRNA, ↑COX-2 mRNA, ↑MCP-1 mRNA, ↑iNOS mRNA, ↓IL-10 mRNA, ↑TLR4, ↑NLRP3, ↑MAPK1, ↑NF-kB-related proteins expression, ↓ZO-1, ↓occludin, and ↓claudin-1	IL-1β mRNA, ↓IL-6 mRNA, ↓TNF-a mRNA, ↓COX-2 mRNA, ↓MCP-1 mRNA, ↓iNOS mRNA, ↑IL-10 mRNA, ↓TLR4, ↓NLRP3, ↓MAPK1, ↓MyD88, ↓p-NF-kB-P65	[36]
Astragalin	DSS-induced C57BL/6 mice model of colitis	200 µL of 50, 75, and 100 mg/kg/day orally for 7 days	↑DAI, ↑intestinal mucosal injury, ↑inflammatory cells infiltration, and ↓colon length	↑TLR4 mRNA,↑MCP-1 mRNA, ↑IL-1β mRNA, ↑TNF-α mRNA, ↑COX-2 mRNA, ↑IFN-γ mRNA, ↑p-IκBα, ↑p-IKKα/β, and ↑p-p65	↓TLR4 mRNA, ↑ZO-1 mRNA, ↑occludin mRNA, ↑Muc2 mRNA, ↓p-IκBα, ↓p-IKKα/β, and ↓p-p65, ↓MCP-1 mRNA, ↓IL-1β mRNA, ↓TNF-α mRNA, ↓COX-2 mRNA, ↓IFN-γ mRNA	[37]
	TNF-α -stimulated HCT-116 and HT-29 human colonic epithelial cells in vitro and DSS-induced C57BL/6 mice model of colitis in vivo	0, 20, 40, 60, 80, and 100 μM incubated for 24 h in vitro and 2 and 5 mg/kg/day orally for 7 days in vivo	↑Pro-inflammatory cytokines production and ↑colon cells proliferation in vitro and ↓colon length, ↑pro-inflammatory cytokines production, and weight loss in vivo	↑Cells proliferation, ↑TNF-α mRNA, ↑IL-8 mRNA, ↑IL-6 mRNA, ↑IκBα phosphorylation, and ↑NF-kB-DNA binding in vitro and ↑IκBα phosphorylation, ↑TNF-α mRNA, ↑IL-8 mRNA, and ↑IL-6 mRNA in vivo	↓Cells proliferation, ↓TNF-α mRNA, ↓IL-8 mRNA, ↓IL-6 mRNA, ↓IκBα phosphorylation, and ↓NF-kB-DNA binding in vitro and ↓IκBα phosphorylation, ↓TNF-α mRNA, ↓IL-8 mRNA, and ↓IL-6 mRNA in vivo	[38]
Pinocembrin	LPS-stimulated RAW264.7 and Caco-2 cells in vitro and DSS-induced C57BL/6 mice model of colitis in vivo	0–200 μM incubated for 24 h in vitro and 25, 50, and 100 mg/kg/day orally for 9 days in vivo	↑Inflammation in vitro and weight loss, ↑intestinal tissue damage, ↑mucosa muscle thickness, ↑neutrophil infiltration, ↑diarrhea, ↑microbiota alterations, and ↑blood in stool in vivo	↑TNF-α, ↑COX-2, ↑iNOS, ↑IFN-γ, ↑IL-6, ↑IL-15, ↑TLR4, ↑p65 phosphorylation, ↑IκBα phosphorylation, and ↓NO in vitro and ↑p65 phosphorylation, ↑TLR4 mRNA, ↑Myd88 mRNA, ↑iNOS mRNA, ↑COX-2 mRNA, ↑TNF-α mRNA	↓Pro-inflammatory cytokines expression, ↓NF-kB-luciferase activity and ↓TLR4/MD2 · LPS interaction in vitro and ↓TLR4 mRNA, ↓Myd88 mRNA, ↓iNOS mRNA, ↓COX-2 mRNA, ↓TNF-α mRNA, and ↓p65 phosphorylation in vivo	[39]
Oxyberberine Bacterial metabolite	DSS-induced BALB/c mice model of colitis	12.5, 25, and 50 mg/kg/day orally/7 days	Shaggy hair, low vitality, body weight loss, diarrhea, occult fecal blood, and ↑DAI	↑MPO, ↓ZO-1, ↓ZO-2, ↓occludin, ↓JAM-A, ↓claudin-1, ↑IL-6, ↑IL-1β, ↑IL-17, ↑TNF-α, ↑IFN-γ, ↑TLR4, ↑MyD88, ↑p-IκBα, ↑p65 (nucleus), ↓IκBα, ↓p65 (cytoplasm)	↓MPO, ↑ZO-1, ↑ZO-2, ↑occludin, ↑JAM-A, and ↑claudin-1 expressions, ↓IL-6, ↓IL-1β, ↓IL-17, ↓TNF-α, and IFN-γ expressions, ↑p65 (cytoplasm), ↓p65 (nucleus), ↓p-IκBα/IκBα ratio, ↓TLR4, ↓MyD88, ↓NF-kB-p65 translocation, ↓IκBα phosphorylation	[40]
Berberine hydrochloride	DSS-induced Wistar mice model of colitis	10, 30, and 50 mg/kg/day orally/6 weeks	Weight loss, ↓survival rate, ↓colon length, ↓colon weight, ↑DAI, ↓daily activity, anorexia, ↑inflammatory cells infiltration, ↑intestinal edema, and ↑microscopic damage scores	↑IL-1 mRNA, ↑IL-1β mRNA, ↑IL-6 mRNA, ↑IL-12 mRNA, ↑TNF-α, ↑IFN-γ mRNA, ↓IL-4 mRNA, ↓IL-10 mRNA, ↑iNOS, ↑MPO, ↑MDA, ↑p-NF-kB	↓IL-1 mRNA, ↓IL-1β mRNA, ↓IL-6 mRNA, ↓IL-12 mRNA, ↓TNF-α, ↓IFN-γ mRNA, ↑IL-4 mRNA, ↑IL-10 mRNA, ↓activity of iNOS, MPO, and MDA, ↓p-NF-kB, ↑p-STAT3 expression, ↑ZO-1 mRNA, ↑VCAM-1 mRNA, ↑occludin mRNA, and ↑claudin-1 mRNA	[41]
Berberine	TNBS-induced C3H/HeN and C3H/HeJ mice models of colitis	10 and 20 mg dissolved in 2% Tween 80 solution/day orally/5 days	Intestinal inflammation measured by shortened, thickened, and erythematous colon	↑Lipid peroxidation, ↓SOD, ↓CAT, ↑TNF-α, ↑IL-1β, ↑IL-6, ↓IL-10, ↑iNOS, ↑COX-2, ↑TLR4, and ↑NF-kB activation (phosphorylation and nuclear translocation)	↓Lipid peroxidation, ↑antioxidant SOD, and CAT expressions, ↓pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 expressions, ↑IL-10 expression, ↓iNOS, and ↓COX-2 activities, ↓TLR4 expression, and ↓NF-kB activation (phosphorylation and nuclear translocation)	[42]
Eriodictyol	TNBS-induced Wistar mice models of colitis	5, 20, and 50 mg/kg/day orally/7 days	Weight loss, colon crypt destruction, mucosal ulceration, and colon inflammatory cells infiltration	↑MPO, ↑IL-6, ↑IL-1β, ↑IL 12, ↑IL-2, ↑TNF-α, ↓IL-10, ↓SOD, ↓CAT, ↓GSH-Px, ↑MDA, ↑TLR4, ↑p-IκBα, ↑p-p65, and ↓IκBα	↓MPO activity, ↓pro-inflammatory cytokines IL-6, IL-1β, IL-12, IL-2, and TNF-α expressions, ↑IL-10 expression, ↑antioxidant enzymes SOD, CAT, and GSH-Px expressions, ↓MDA expression, ↓p65 phosphorylation, ↓IκBα phosphorylation, and ↑IκBα	[43]
Betulin	Acetic acid-induced Sprague Dawley mice models of colitis	8 mg/kg/day intraperitoneally for 14 days	Diffuse necrosis, congestion, and hemorrhage of the mucosal layer and submucosal edema, congestion, and immune/inflammatory cells infiltration	↑CRP, ↑LDH activity, ↑TLR4, ↑CD68 cells infiltration, ↑IL-6, ↑NF-kB expression, ↑TNF-α, ↑IL-1β, ↑caspase-3, and ↑caspase-8	↓LDH activity, ↓TLR4 content, ↓CD68 cells infiltration, ↓IL-6 content, ↓NF-kB expression, ↓TNF-α expression, ↓IL-1β, ↓caspase-3 expression, and ↓caspase-8 expression	[44]
Naringin	LPS-stimulated RAW264.7 cells in vitro and DSS-induced mice model of colitis in vivo	20 μM incubated for 1 h in vitro and 25, 50, and 100 mg/kg/day orally for 7 days in vivo	↑Intestinal inflammation in vitro and ↑intestinal mucosa injury and ↑DAI in vivo	↑TNF-α, ↑NF-kB activation, ↓PPARγ expression in vitro and ↑TNF-α, ↑IL-1β, ↑IL-6, ↑NF-kB-p65 phosphorylation, ↑IκB phosphorylation, ↓PPARγ expression, ↑MAPK, ↑NLRP3, ↑ASC, and ↑caspase-1 in vivo	↓TNF-α, ↓NF-kB activation, and ↑PPARγ expression in vitro and ↓pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 expressions, ↓NF-kB-p65 phosphorylation, ↓IκB phosphorylation, ↑PPARγ expression, ↓phosphorylation levels of p38, ERK, and JNK, ↓NLRP3, ↓ASC, and ↓caspase-1 in vivo	[45]
5-Hydroxy-4-methoxycanthin-6-one	DSS-induced Sprague Dawley mice model of colitis	25, 50, and 100 mg/kg/day orally for 11 days	Weight loss, ↑DAI, ↓colon length, epithelial crypts destruction, disruption of the mucosal barrier, and massive submucosal infiltration of inflammatory cells	↑TNF-α, ↑IL-1β, ↑IL-6, ↓IL-10, ↓SOD, ↑MDA, ↑NF-kB/p65, ↑CD3, ↑MYD88, ↑p-IκBα, ↓IKKβ, ↓IκBα, ↑NF-kB/p65 nuclear translocation	↑SOD, ↓MDA, ↓TNF-α, ↓IL-1β, ↓IL-6 and ↑IL-10 expression levels, ↓NF-kB/p65 and ↓CD3 pro-inflammatory phenotypes, ↓NF-kB/p65 mRNA, ↓MYD88, ↓p-IκBα, ↑IKKβ and ↑IκBα proteins expression, ↓NF-kB/p65 nuclear translocation	[46]
Geniposide	LPS-stimulated RAW264.7 cells in vitro and DSS-induced ICR mice model of colitis in vivo	200–1000 μM incubated for 24 h in vitro and 20 and 40 mg/kg/day orally/7 days in vivo	↓Cells viability in vitro and weight loss, ↑erosion and ↑distortion of crypts, ↑loss of glandular epithelium, and ↑inflammatory cell infiltration in vivo	↓SOD, ↑IL-1β, ↑IL-6, ↑TNF-α, ↑ROS, ↓HO-1, ↓Nrf2 activation, ↑p-NF-kBp65 and ↑p-IκBα in vitro and ↑MPO, ↓SOD, ↑IL-1β, ↑IL-6, ↑TNF-α, ↑inflammatory cells infiltration, ↓HO-1, ↓Nrf2 activation, ↑p-NF-kBp65 and ↑p-IκBα in vivo	↑SOD, ↓IL-1β, ↓IL-6, ↓TNF-α, ↓ROS, ↑HO-1, ↑Nrf2 activation, ↓p-NF-kBp65, and ↓p-IκBα in vitro and ↓MPO, ↑SOD, ↓IL-1β, ↓IL-6, ↓TNF-α, ↓inflammatory cells infiltration, ↑HO-1, ↑Nrf2 activation, ↓p-NF-kBp65 and ↓p-IκBα in vivo	[47]
Sesamin	DSS-induced C57BL/6 mice model of colitis	50, 100, and 200 mg/kg/day orally/7 days	↓Colon length and ↓body weight	↑TNF-α, ↑IL-1β, ↑IL-6, ↑p-NF-kBp65, ↑p-IκBα, ↑NF-kB signaling and activity and ↑MAPK	↓TNF-α, ↓IL-1β, ↓IL-6, ↓p-NF-kBp65, and ↓p-IκBα expression levels, ↓NF-kB signaling and activity, and ↓MAPK levels	[48]
Taxifolin	DSS-induced ICR mice model of colitis	100 mg/kg/day orally for 14 days	↑DAI, ↓colon length, ↓body weight, ↑crypt distortion, and ↑inflammatory cells infiltration	↑TNF-α, ↑IL-1β, ↑IL-6, ↓SIgA, ↓IL-10, ↓SOD, ↑p-NF-kB-p65 and ↑p-IkBα	↓TNF-α, ↓IL-1β and ↓IL-6 expression levels, ↑SIgA, ↑IL-10 and ↑SOD expression levels, ↓p-NF-kB-p65 and ↓p-IkBα	[49]
Isobavachalcone	DSS-induced C57BL/6 mice model of colitis	25 and 50 mg/kg/day orally/4 days	↓Body weight, ↑DAI, ↑crypt distortion, ↑mucosal necrosis, ↑edema, ↑gland destruction, and ↑neutrophilic infiltration	↑MPO, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑PGE2, ↑NO, ↑iNOS, ↑COX-2 and ↑p-NF-kB-p65	↓MPO, ↓TNF-α, ↓IL-1β, ↓IL-6, ↓PGE2, ↓NO, ↓iNOS and ↓COX-2 expression levels and ↓p-NF-kB-p65	[50]
d-pinitol	DSS-induced BALB/c mice model of colitis	10, 20, and 40 mg/kg/day orally/7 days	↓Body weight, ↑DAI, ↑ulcer formation, ↑thickened bowel wall, ↑hyperemia, ↑edema, and ↑mucosal inflammatory cells infiltration	↑MPO, ↑MDA, ↓GSH, ↓SOD, ↓CAT, ↑iNOS, ↑COX-2, ↑TNF-α, ↑IFN-γ, ↑IL-6, ↑IL-17, ↑IL-1β, ↓IL-10, ↓PPAR-γ and ↑NF-kB signaling	↓MPO, ↓MDA, ↑GSH, ↑SOD, ↑CAT, ↓iNOS, ↓COX-2, ↓TNF-α, ↓IFN-γ, ↓IL-6, ↓IL-17, ↓IL-1β, ↑IL-10, ↑PPAR-γ and ↓NF-kB signaling	[51]
Paeoniflorin-6’-O-benzene sulfonate	DSS-induced mice model of colitis	17.5, 35, and 70 mg/kg/day orally/6 days	↑M1 macrophage polarization and ↑intestinal barrier dysfunction	↑GRK2 activation and ↑TLR4-NF-kB-NLRP3 inflammasome signaling	↓GRK2 translocation and ↓TLR4-NF-kB-NLRP3 inflammasome signaling in macrophages	[52]
Thymol	AcOH-induced Wistar mice model of colitis	10, 30, and 100 mg/kg/day orally/6 days	↑Intestinal inflammation and ↑OS	↑MPO, ↑TNF-α, and ↑p-NF-kB-p65	↓MPO, ↓TNF-α, and ↓p-NF-kB-p65	[53]
Tricin	DSS-induced BALB/c mice model of colitis and LPS-induced RAW 264.7 treated cells	12.5, 25, and 50 µM incubated/30 min or 24 h in vitro and 100 and 150 mg/kg/day orally/7 days in vivo	↑ DAI, ↓Body weight, ↓colon length, ↑Inflammatory cells infiltration, ↑epithelial cell disorganization, ↑mucosal thickening, ↓crypts, ↑spleen weight, and ↑myeloid-derived suppressor cells (MDSC, CD11b+Gr1+), ↑MPO, ↑IL-6, TNF-α, and IL-1β in colonic tissues in vivo	↑NO, ↑IL-6, ↑TNF-α, ↑IL-1β, ↑MIP-2, ↑phosphorylated NF-kB-p65 in vitro	↓IL-6 expression, ↓TNF-α expression, ↓MIP-2 expression, ↓IL-1β expression ↓Phosphorylated nuclear p65 in vitro and ↓NF-kB pathway in vivo	[54]
Aesculin	DSS-induced BALB/c mice model of colitis and LPS-induced RAW 264.7 treated cells	200, 300, 400, and 500 µM incubated for 1 h in vitro and 1 and 5 mg/kg/day intraperitoneally every two days after colitis induction for 12 days in vivo	↓Body weight, ↑DAI, ↑colon length, ↑colon weight, ↑inflammatory cells infiltration (mononuclear macrophages and neutrophils), ↑mucosal and submucosal lesion, ↑degeneration, and ↑crypt cells necrosis	↑p-p65, ↑IκBα phosphorylation and ↓PPAR-γ in vitro and ↑iNOS mRNA, ↑TNF-α mRNA, ↑IL-1β mRNA, ↑p-P65, ↑MAPKs protein and phosphorylation in vivo	↓TNF-α mRNA, ↓IL-1β mRNA, ↓p-P65, ↓IκBα phosphorylation, ↑PPAR-γ, ↓NK-kB activation in vitro and ↓iNOS mRNA, ↓TNF-α mRNA, ↓IL-1β mRNA, ↓NK-kB activation in vivo	[55]
Ginsenoside Rk3	HFD-induced obese C57BL/6 mice model of colitis	30 and 60 mg/kg/day orally/8 weeks	↑Body weight, ↑fat accumulation, ↑glucose tolerance, ↓colon length, ↑inflammatory cells infiltration and ↑crypt lesions	↓ZO-1 mRNA, ↓claudin mRNA, ↓occludin mRNA,↑TLR4, ↑MYD88, and ↓IkBα	↑ZO-1 mRNA, ↑claudin mRNA, ↑occludin mRNA, ↓TNF-α mRNA, ↓IL-1β mRNA, ↓IL-6 mRNA, ↓MCP-1 mRNA, ↓F4/80 mRNA, ↓NADPH mRNA, ↓STAMP2 mRNA, ↓TLR4, ↓JNK/phosphorylation JNK, ↓NF-kB, ↓TLRA4/MYD88 pathway, and ↑IkBα mRNA	[56]
Lancemaside A	TNBS-induced ICR mice model of colitis and LPS-induced 293-hTLR4A-hemagglutinin treated cells	20 μM and 100μM incubated for 6 h in vitro and 10 or 20 mg/kg/day orally for 5 days in vivo	↓Colon length, ↑thicken, ↑erythematous colon, ↑edema, ↑inflammatory cells infiltration, and ↑epithelial ulcers	↑TLR4-linked NF-kB in vitro and ↑MPO, ↑TNF-α mRNA and ↑IL-1β mRNA, ↑IL-6 mRNA, ↑TLR4 mRNA, ↑NF-kB (pp65) mRNA, ↑COX-2 mRNA in vivo	↓TLR4-linked NF-kB in vitro and ↓TNF-α mRNA, ↓IL-1β mRNA, ↓IL-6 mRNA, ↓TLR4 mRNA, ↓NF-kB-p65 mRNA and ↓COX-2 mRNA in vivo	[57]
Tetramethylpyrazine	Oxazolone-induced KM mice model of colitis and LPS-treated Caco-2 cells	40 µg/mL incubated for 24 h in vitro and 80 mg/kg/day intraperitoneally/7 days in vivo	↓Body weight, ↑diarrhea with or without hematochezia, ↑DAI, ↑inflammation of the mucosa, ↑fibrotic thickening, ↑ulcers, ↑edema, ↑microhemorrhages, and ↑ necrosis	↑NF-kB translocation into the nucleus, ↓NF-kB P65 protein in the cytoplasm, ↑nuclear NF-kB P65 protein levels, ↑TNF- α, ↑IL-6, ↑IL-8, ↑INF-γ mRNA and ↑ROS in vitro, and ↑NF-kB P65 in the nucleus, ↓NF-kB in cytoplasmic, ↑C-MYC expression, ↑iNOS expression, ↑COX-2 expression in vivo	↓NF-kB translocation into the nucleus, ↑NF-kB P65 protein in the cytoplasm, ↓nuclear NF-kB P65 protein levels, ↓INF-γ expression, ↑P65 in the cytoplasm, ↓P65 in the nucleus in vitro and ↓NF-kB P65 in the nucleus, ↓p-IKBα, ↑NF-kB in the cytoplasm, ↓nuclear NF-kB p65 protein levels, ↓C-MYC expression, ↓iNOS expression and ↓COX-2 expression in vivo	[58]
Daurisoline	DSS-induced BALB/c mice model of colitis and LPS-induced RAW 264.7 treated cells	0, 0.5, 1, 2, 5, 10, 20, 50, and 100 μM incubated for 24 h in vitro and 10, 20, 40 mg/kg/day orally/7 days in vivo	↑DAI, ↑diarrhea, ↑bleeding, ↓colon length, ↑edema, ↑congestion, ↑thickening, ↑erosion, ↑ulceration, ↑adhesions to adjacent tissues, ↑mucosal damage, ↑inflammatory cell infiltration, ↑crypt loss, and ↑TUNEL stained spots	↑NO, ↑ROS, ↓GSH, ↑NF-kB-p65, ↑p65, ↓IkBα in vitro and ↑NO, ↑ COX-2, ↑PGE2, ↑IL-1β, ↑MMP-9, ↓IL-4, ↓IL-10, Gene expression of ↑Wnt-1, ↑β-Catenin, ↑cyclin-D1, ↑C-MYC, ↑Expression of Wnt-1, β-Catenin and LRP6, ↓Expression of p-GSK3β and ↑Expression of NF-kB p65 and p-IkBα in vivo	↓NF-kB p65, ↓p65, ↑IkBα in vitro and Gene expression of ↓Wnt-1, ↓β-Catenin, ↓cyclin-D1, ↓C-MYC, ↓GSK3β, ↑Expression of TCF-4, LEF-1 and p-GSK3β, ↓Expression of Wnt-1, β-Catenin and LRP6 and ↓expression of NF-kB p65 and p-IkBα in vivo	[59]
Tetrandrine	DSS-induced BALB/c mice model of colitis	40 mg/kg/day orally/7 or 14 days	↑DAI	↑NF-kB DNA binding activity, ↑IL-1β mRNA and protein, ↑TNF-α mRNA and protein, and ↑MPO	↓NF-kB DNA bindng activity, ↓IL-1β mRNA and protein, ↓TNF-α mRNA and protein	[60]
Diosgenin	TNBS-induced Sprague-Dawley rat model of colitis	50, 100, or 200 mg/kg/day orally/14 days	↑DAI, ↓body weight, ↑colonic damage, ↑ulceration, ↑stool consistency score, ↑destruction of colon tissue, ↑inflammatory cell infiltration, ↑necrosis and ↑edema	↓GSH, ↓SOD, ↑MDA, ↑NO, ↑MPO, ↑hydroxyproline, ↑TNF-α, ↑IL-1β, ↑IL-6, ↓IL-10, ↑iNOs mRNA, ↑IFN-γ mRNA, ↑COX-2 mRNA, ↑LTB4 mRNA, ↑Bax, ↑Caspase-1, ↑NF-kB and ↑IκBα,	↓iNOs mRNA, ↓COX-2 mRNA, ↓IFN-γ mRNA, ↓Bax, ↓Caspase-1, ↓NF-kB and ↓IκBα	[61]
Mangiferin	TNBS-induced C57BL/6 mice model of colitis and LPS-induced peritoneal macrophages	5, 10, and 20 μM incubated for 15 to 120 min in vitro and 10 or 20 mg/kg/day orally/3 days in vivo	↓Colon length, ↑MPO	↑IRAK1 phosphorylation and degradation, ↑degradation of IRAK1, 2, and 4, ↑NF-kB activation, ↑TAK1 phosphorylation and degradation, ↑IKKβ phosphorylation, ↑IκBα phosphorylation and degradation, ↑PGE2, ↑NO, ↑TNF-α expression, ↑IL-1β expression, ↑IL-6 expression, ↑IL-10 expression, ↑COX-2, ↑iNOS expression in vitro and ↑IRAK1 phosphorylation in vivo	↓IRAK1 phosphorylation and degradation, ↓NF-kB activation, ↓IKKβ phosphorylation, ↓IκBα phosphorylation and degradation, ↓p65 translocation, ↓MAPK p38 phosphorylation, ↓ERK phosphorylation, ↓JNK phosphorylation, ↓TNF-α expression, ↓IL-1β expression, ↓IL-6 expression, ↓COX-2 expression, ↓iNOS expression and ↑IL-10 expression in vitro and ↓phosphorylation of IRAK1 and IKKβ, ↓NF-kB activation, ↓TNF-α expression, ↓IL-1β expression and ↓IL-6 expression in vivo	[62]
Tryptanthrin	DSS-induced mice model of colitis	39.2, 78.4, and 156.8 mg/kg twice a day orally/8 days	↑CAS, ↓crypts and goblet cells, ↑erosive lesions, ↑inflammatory cell infiltration, and ↑atrophy	↑TNF-α, ↑IL-1β, ↑IL-6, ↓IL-10, ↑NF-kBp65, ↑p-STAT3, ↓IκBα protein, ↑STAT3 and ↑p-STAT3	↓NF-kBp65, ↓p-STAT3, and ↓IκBα degradation	[63]
l-Theanine	DSS-induced C57BL/6J mice model of colitis	Water contained 0.1% of l-theanine for 14 days orally	↓Body weight, ↓length of colon, ↓colon weight, ↑DAI, ↑inflammatory infiltrates, and ↑epithelial injury	↑TNF-α, ↑IL-1β, ↑IL-6, ↑COX2 mRNA, ↑iNOS mRNA, ↓Ki67-positive cells, ↑TUNEL-positive cells, ↓Occludin mRNA, ↓Claudin1 mRNA, ↓Ecadherin mRNA, ↑ p65, ↑p-p65, ↑p53, ↑p-p53 and ↑p-AKT expression and ↑lipid metabolic perturbation	↓COX2 mRNA, ↓iNOS mRNA, ↑Occludin mRNA, ↑Claudin1 mRNA, ↑Ecadherin mRNA, ↓p65, ↓p-p65, ↓p53, ↓p-p53, and ↓p-AKT expression	[64]
Koreanaside A	LPS-induced RAW 264.7 and peritoneal macrophages treated cells and DSS-induced ICR mice model of colitis	20, 40, or 80 µM in vitro incubated/4 days and 5 or 20 mg/kg/day orally/7 days in vivo	↑DAI, ↑body weight loss, ↑stool consistency, ↑occult fecal blood, ↓colon length, ↑spleen index, ↑mucosal layer, ↑ulceration, ↑crypt loss, and ↑inflammatory cell infiltration	↑NO, ↑PGE2, ↑expression of iNOS and ↑ expression of COX-2, ↑IL-6 mRNA, ↑TNF-α mRNA, ↑AP-1, ↑DNA-binding activity of NF-kB in vitro and ↑F4/80 mRNA, ↑Ly6G mRNA, ↓ZO-1 mRNA, ↓occludin mRNA, ↑claudin-1 mRNA, ↓E-cadherin mRNA, ↑N-cadherin mRNA, ↑vimentin mRNA, ↑iNOS mRNA, ↑COX-2 mRNA, ↑IL-6 mRNA, ↑TNF-α mRNA, ↑c-Fos, ↑p65, STAT1 and ↑STAT3 phosphorylation in vivo	↓iNOS expression and ↓COX-2 expression, ↓IL-6 mRNA, ↓TNF-α mRNA, ↓MyD88-dependent TLR4 pathway, ↓DNA binding of AP-1, ↓DNA-binding activity of NF-kB, ↓c-Fos phosphorylation, ↓phosphorylation and nuclear translocation of p65. ↓phosphorylation and degradation of IκBα, ↓phosphorylation of IKKα/β, ↓phosphorylation of TAK1, ↓STAT1 (Y701 and S727), ↓STAT3 (Y705), ↓JAK1 (Y1022), JAK2 (Y1007/1008) phosphorylation in vitro and ↓F4/80 mRNA, ↓Ly6G mRNA, ↑ZO-1 mRNA, ↑occludin mRNA, ↓claudin-1 mRNA, ↑E-cadherin mRNA, ↓N-cadherin, ↓iNOS mRNA, ↓COX-2 mRNA, ↓IL-6 mRNA, ↓TNF-α mRNA, ↓vimentin mRNA, ↓↑c-Fos, p65, STAT1 and ↑STAT3 phosphorylation in vivo	[65]
6-gingerol	DSS-induced BALB/c mice model of colitis	100 and 250 mg/kg/day orally/14 days	↓Body weight, ↓crypt cells, ↓goblet, ↑granulation, ↑hyperplasia, and ↑inflammatory cells infiltration	↑IL-17, ↓IL-10, ↑IkBα, ↑p65, ↑p-IκBα and ↑p-p65	↓IkBα, ↓p65, ↓p-IκBα and ↓p-p65	[66]
Lycopene	DSS-induced C57BL/6 mice model of colitis	5, 10, and 20 mg/kg/day orally/14 days	↓Body weight, ↑DAI, ↑colon length, ↑colon weight, ↑glandular disorder, and ↑inflammatory cell infiltration	↑MPO, ↓SOD, ↓ CAT, ↓GSH-Px, ↑MDA, ↑IFN-γ, ↑TNF-α, ↑IL-6, ↑IL-1β, ↑TLR4, ↑TRIF, and ↑p-NF-kB p65 expression, ↓ZO-1, ↓occludin, and ↓claudin-1 expressions	↓TLR4, ↓TRIF, ↓p-NF-kB p65 expression, ↑ZO-1, ↑occludin and ↑claudin-1 expressions	[67]
α-mangostin	DSS-induced mice model of colitis	30 and 100 mg/kg/day orally/14 days	↓Body weight, ↑DAI, ↑diarrhea, ↑bleeding, ↓colon length, ↑ulceration, ↑erosion, ↑crypt distortion, ↑inflammatory cell infiltration, and ↑edema	↑MPO, ↑phosphorylation of IKKα and IκB, ↑activated NF-kB, ↑MAPK, ↑phosphorylation of ERK1/2, SAPK/JNK and p38	↓IKKα phosphorylation, ↓IκBα phosphorylation, ↓activated NF-kB, ↓phosphorylation of ERK1/2, SAPK/JNK and ↓p38	[68]
Ophiopogonin D	DSS-induced C57BL/6J mice model of colitis and LPS-induced IEC-6 treated cells	10 mg/kg and 40 mg/kg/day orally/7 days in vivo 20 μmol/L incubated for 24 h in vitro	↑Ulceration, ↑congestion, ↑edema, ↑inflammatory cell infiltration, ↓colon length, and ↓body weight	↑cl-caspase3 and ↑COX-2, ↑MLCK and ↑iNOS in vitro and ↑TNF-α, ↑IL-6, ↑IL-1β, ↓Bcl-2, ↓occludin, ↑NF-Κb-p65, ↑cl-caspase3, ↑Bax, ↑MLCK, ↑MDA, ↓GSH, ↓SOD, ↑iNOS, ↑COX-2 in vivo	↓NF-Κb-p65 in vivo and in vitro	[69]
Alantolactone	DSS-induced C57BL/6 mice model of colitis and LPS-induced RAW 264.7 and HT-29 colorectal treated cells	0–25 μM incubated for 2 h in vitro 50 mg/kg/day orally/9 days in vivo	↓Body weight, ↓bloody diarrhea, ↓colon length, ↑histological injury, ↑inflammatory cell infiltration	↑p-p65 nuclear translocation in vitro and ↑NF-kB p65 phosphorylation, ↑IκBα phosphorylation/degradation, ↑iNOS expression, ↑ICAM-1 expression, ↑MCP-1 expression, ↑COX-2 expression, ↑TNF-α expression, ↑IFN-γ expression, ↑IL-6 expression, ↑MPO, ↑ NO, ↑PGE2, ↑TNF-α, ↑IL-6 in vivo	↓p-p65 nuclear translocation, ↑hPXR via binding to hPXR-LBD in vitro and ↓NF-kB p65 phosphorylation, ↓IκBα phosphorylation/degradation, ↓iNOS expression, ↓ICAM-1 expression, ↓COX-2 expression, ↓TNF-α expression, ↓IFN-γ expression and ↓IL-6 expression in vivo	[70]
Sinomenine	DSS-induced BALB/c mice model of colitis	30, 90, 270, 180, 540 mg/kg/day and 1.6 g/kg/day orally/9 days	↓Body weight, ↓food intake, ↑pasty stools, ↑DAI, ↓colon length, and ↑inflammatory cell infiltration	↑MyD88, ↑NF-kBp65, ↑TLR4, ↓SIGIRR expression, ↑TLR/NF-kB	↓MyD88 expression, ↓NF-kBp65 expression, ↓TLR expression, ↑SIGIRR expression, ↓TLR/NF-kB, ↓expression of IFN-γ, IL-1β, TNF-α, IL-6, and IL-12	[71]
Convallatoxin	LPS-induced RAW264.7 and BMDMs macrophages and DSS-induced C57BL/6 mice model of colitis	10–50 nM incubated for 12 or 24 h in vitro and 50 or 150 μg/kg/day orally/10 days in vivo	↓Colon length, ↑colon and spleen weights, ↓body weight, ↑inflammatory cell infiltration, ↑ulceration, ↑necrosis, ↑congestion and ↑edema, ↑IL-1β, IL-6, and TNF-α in the colon	↑NF-kB, ↑COX-2, ↑iNOS, ↑ IL-1β, ↑ IL-6, ↑TNF-α, ↑NF-kB-p65 and ↓PPARγ in vitro and ↑COX-2, ↑iNOS, ↑IL-1β, ↑IL-6, ↑TNF-α, ↑nuclear NF-kB-p65, ↓PPARγ protein in vivo	↓NF-kB p65, ↑PPARγ, ↑PPARγ mRNA, ↓NF-kB mRNA, ↓IL-1β mRNA, ↓IL-6 mRNA, ↓TNF-α mRNA, ↓p-IκBα, ↑PPARγ siRNA in vitro and ↓nuclear NF-kB-p65, ↑PPARγ expression, ↓nuclear translocation of NF-kB-p65, ↓cytoplasmic p-IκBα expression, ↑PPARγ mRNA and ↓NF-kB mRNA in vivo	[72]
Fisetin	DSS-induced Balb/C mice model of colitis and LPS-induced macrophages treated cells	5 and 10 mg/kg/day orally/8 days in vivo and 0–50 μM incubated for 24 h in vitro	↑DAI, ↓body weight, ↓colon length, ↓crypts, ↓goblet cells, ↑inflammatory cell infiltration,	↑Nitrites, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑COX-2, ↑iNOS, ↑NF-kB-p65 nuclear translocation, ↑IkBα phosphorylation and degradation in vitro and ↑MPO, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑Nitrites, ↑COX-2, ↑iNOS, ↑nuclear NF-kB (p65), ↑phosphorylation of IκBα (p-IκBα/IκBα), ↑NF-kB (p65)-DNA binding activity, ↑p-p38/p38, ↑p-ERK/ERK, ↑Akt phosphorylation, ↓GSH, and ↑TBARS in vivo	↓NF-kB-p65e expression, ↓IkBα phosphorylation and degradation in vitro and ↓nuclear NF-kB (p65), ↓phosphorylation of IκBα (p-IκBα/IκBα), ↑NF-kB (p65)-DNA binding activity, ↓p-p38/p38, ↑p-ERK/ERK, and ↓Akt phosphorylation in vivo	[73]
Genipin	DSS-induced C57BL/6 mice model of colitis	2.5, 5, 10 mg/kg/day orally/14 days	↓Body weight, ↑intestinal epithelial destruction, ↑crypt abscesses, and ↑goblet cells loss	↑MPO, ↑MDA, ↑TNF-α, ↑IL-1β, ↑NF-kB signaling, ↓Nrf2 signaling and ↓HO-1	↓MPO, ↓MDA, ↓TNF-α and ↓IL-1β expression, ↓NF-kB signaling, ↑Nrf2 signaling and ↑HO-1 expression	[74]
Piperine	TNBS-induced Sprague–Dawley mice model of colitis	10, 20, and 40 mg/kg/day orally/14 days	↓Body weight, ↑colon weight-to-length ratio, and ↑ulceration	↑Oxide-nitrosative stress, ↑iNOS, ↑TNF-α, ↑IL-1β, ↑IFN-γ, ↑COX-2 mRNA, ↑LTB4, ↑IkBα, ↑NF-kB signaling, ↓occludin, ↓claudin-1, ↓zonula occludens-1, ↑caspase-1 and ↓IL-10	↓Oxide-nitrosative stress, ↓iNOS, ↓TNF-α, ↓IL-1β, ↓IFN-γ, ↓COX-2 mRNA, ↓LTB4 and ↓IkBα expression levels, ↓NF-kB signaling, ↑occludin, ↑claudin-1, ↑zonula occludens-1 and ↑IL-10 expression levels and ↓caspase-1	[75]
Ligustilide	DSS-induced C57BL/6 mice model of colitis	15, 30, and 60 mg/kg/day orally/14 days	↓Body weight and ↓colon length, ↑diarrhea, ↑rectal bleeding, ↑ulceration, and ↑inflammatory cells infiltration	↑MPO, ↑iNOS, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑IL-12, ↑MIP-1α, ↑IL-17, ↓PPARγ and ↑NF-kB-p65	↓MPO, ↓iNOS, ↓TNF-α, ↓IL-1β, ↓IL-6, ↓IL-12, ↓MIP-1α and ↓IL-17 expression levels, ↑PPARγ expression and signaling and ↓NF-kB-p65 expression	[76]
Evodiamine	DSS-induced C57BL/6 mice model of colitis	20, 40, and 80 mg/kg/day orally/10 days	↑Diarrhea, ↑fecal bleeding, ↑colon shortening, and ↓body weight	↑MPO, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑p-NF-kB p65, ↑p-IkB, ↑NLRP3, ↑ASC, ↑caspase-1, ↓ZO-1 and ↓occludin	↓MPO, ↓TNF-α, ↓IL-1β, ↓IL-6, ↓p-NF-kB p65, ↓p-IkB, ↓NLRP3, ↓ASC, ↓caspase-1, ↑ZO-1 and ↑occludin	[77]
Chrysin	TNBS-induced C57BL/6 mice model of colitis	25 mg/kg/day orally/10 days	↓Body weight, ↑diarrhea, ↑fecal bleeding, ↑crypt distortion, and ↑inflammatory exudate	↑p-65, ↑IkBα phosphorylation and degradation, ↑NF-kB nuclear translocation, ↑iNOS mRNA, ↑ICAM-1 mRNA, ↑MCP-1 mRNA, ↑COX-2 mRNA, ↑TNF-α mRNA, ↑IL-6 mRNA, and ↑MPO	↓p-65, ↓IkBα phosphorylation and degradation, ↓NF-kB nuclear translocation, ↓iNOS mRNA, ↓ICAM-1 mRNA, ↓MCP-1 mRNA, ↓COX-2 mRNA, ↓TNF-α mRNA, ↓IL-6 mRNA, and ↓MPO	[78]
Wogonoside	DSS-induced BALB/c mice model of colitis and LPS-induced Human acute monocytic leukemia THP-1 treated cells	12.5, 25, or 50 mg/kg/day orally/10 days in vivo and 0.1 mM incubated for 4 h in vitro	↓Body weight, ↓colon length, ↓spleen weight, ↑inflammatory cell infiltration, ↑ulcers, ↑edema and ↑congestion, ↑CD11b+ F4/80+ macrophages and ↑CD11b+ Gr-1+ neutrophils,	↑NLRP3 mRNA and ↑pro-caspase-1 mRNA in vitro and ↑IL-1β, ↑TNF-α, ↑IL-6, ↑NF-kB p65, ↑cleaved caspase-1 (p10), ↑cleaved-IL-1β, ↑NLRP3 and ↑ASC in vivo	↓IL-1β mRNA, ↓TNF-α mRNA, ↓IL-6 mRNA, ↓NF-kB nuclear translocation, ↓IkBa phosphorylation, ↓phosphorylation of p65, ↓NF-kB DNA binding activity, ↓NLRP3 mRNA and ↓pro-caspase-1 mRNA in vitro and ↓NF-kB, ↓NF-kB-p65, ↓IkBa phosphorylation, ↓p65, ↓p65 phosphorylation and ↓NF-kB DNA binding activity in vivo	[79]
Oxymatrine	TNBS-induced rats model of colitis	10, 30, or 60 mg/kg/day intraperitoneally/7 days	↓Body weight, ↓colon length, ↑DAI, ↑ulcers, ↓goblet cells, and ↑inflammatory cell infiltration	↓ZO-1 mRNA, ↓occludin mRNA, ↓claudin-2 mRNA, ↑IL-6, ↑TLR9, ↑Myd88 and ↑p-NF-kB P65	↓IL-1β mRNA, ↓TNF-α mRNA, ↓IL-6 mRNA, ↓NF-kB, ↓TLR9 expression, ↓Myd88, ↓TLR9/Myd88/NF-kB pathway	[80]
Epicatechin	DSS-induced C57BL/6J mice model of colitis and LPS-induced RAW264.7 and IEC-6 treated cells	100, 200, or 300 mg/kg/day orally/7 days in vivo and 0.1 µM, 1 µM or 10 µM incubated for 4 h in vitro	↓Body weight, ↓colon length, ↑intestinal bleeding, ↑DAI, and ↑CMDI scores	↑TNF-α, ↑IL-6, ↑NO, ↑MPO and ↑NF-kB	↓NF-kB expression	[81]
Thymoquinone	DSS-induced C57BL/6J mice model of colitis and TNF-α-induced HT-29 treated cells	20 and 40 mg/kg/day orally for 8 days in vivo and 0, 12.5, 50, 100, 150, and 200 µM incubated for 24 h in vitro	↑DAI, ↑inflammatory cells infiltration, ↑MPO, ↓crypts, ↓villi, ↑submucosal edema, and ↑epithelium destruction	↑CXCL-1 mRNA, ↑IL-8 mRNA and COX-2 mRNA in vitro and ↑IL-1β expression, ↑TNF-α expression, ↑IL-6, expression ↑IL-6 mRNA, ↑IL-1β mRNA, ↑TNF-α mRNA, ↑COX-2, ↑iNOS, ↑COX-2 mRNA, ↑iNOS mRNA, ↑p-ERK, ↑p-JNK, ↑p-p38, ↑phosphorylation of the NF-kB protein and ↓PPAR-γ expression in vivo	↓CXCL-1 mRNA, IL-8 mRNA, and COX-2 mRNA, ↑PPAR-γ expression both at protein and mRNA in vitro and ↓IL-6 mRNA, ↓IL-1β mRNA, ↓TNF-α mRNA, ↓p-ERK, ↓p-JNK, ↓p-p38, ↓phospho-NF-kB protein and ↑PPAR-γ in vivo	[82]
Fraxinellone	DSS-induced C57BL/6J mice model of colitis and LPS-induced Human THP-1 treated cells	7.5, 15, 30 mg/kg/ day intraperitoneally/9 days in vivo and 10, 30 µM incubated for 24 h in vitro	↓Body weight, ↑diarrhea, ↑loose feces, ↑visible fecal blood, ↑mortality, ↑gross bleeding, ↑ulcerations, colon length, ↑DAI, ↑inflammatory cell infiltration at mucosa and submucosa, ↑crypts distortion, and ↓goblet cells	↑IL-1β, ↑IL-18, ↑TNF-α, ↑IL-6 in vivo and ↑IL-1β, ↑IL-18 and ↑NO in vitro	↓VCAM1 mRNA, ↓iNOS mRNA, and ↓COX-2 mRNA in vivo and ↓IL-1β expression, ↓IL-18 expression, ↓phosphorylation of IKKα/β, ↓IκBα, ↓phosphorylation of the p65, ↓p65, ↓Caspase-1 activation and ↓NLRP3 inflammasome in vitro	[83]
Artesunate	DSS-induced Sprague-Dawley rats model of colitis and LPS-induced RAW264.7 treated cells	10, 30, and 50 mg/kg/day orally/5 days in vivo and 5, 10, and 20 µg/mL incubated for 24 h in vitro	↑DAI, ↓hemoglobin, ↓colon length, and ↑cell destruction	↑TNF- α, ↑IL-8, ↑IFN-γ, ↑TLR4, ↑p-NF-kB, ↑p-p38, ↑Bax, ↑caspase-9 and ↓Bcl-2	↓TLR4, ↓p-NF-kB, ↓p-p38, ↓Bax, ↓caspase-9 and ↑Bcl-2	[84]
Aesculetin	DSS-induced C57BL/6J mice model of colitis and LPS-induced RAW264.7 treated cells	20 mg/kg/day orally/7 days in vivo and 10, 25, 50 µM incubated for 4 h in vitro	↓Colon length, ↓body weight, ↑DAI, and ↑inflammatory cell infiltration	↑NO, ↑iNOS expression, ↑p–NF–κB-P65 expression, ↑NF-kB P65 nuclear translocation, ↑p38 phosphorylation, ↑JNK phosphorylation, ↑ERK phosphorylation, ↑NLRP3 expression in vitro and ↑NF-kB P65, ↑TNF-α and ↑IL-6 in vivo	↓iNOS expression, ↓p–NF–κB P65 expression, ↓NF-kB-P65 nuclear translocation, ↓p38 phosphorylation, ↓JNK phosphorylation, ↓ERK phosphorylation and ↓NLRP3 expression in vitro and ↓NF-kB-P65, ↓p38 phosphorylation, ↓JNK phosphorylation and ↓ERK phosphorylation in vivo	[85]
Euphol	DSS and TNBS-induced CD1 mice model of colitis and LPS-induced BMDMs treated cells	3, 10, and 30 mg/kg twice a day orally for 3, 4 or 7 days in vivo and 1 and 10 µM incubated for 24 h in vitro	↑Hemorrhage in the colonic lumen, ↓body weight, ↑diarrhea with bloody stools, ↑DAI, ↑mucosal neutrophils infiltration, ↓crypts, ↓goblet cells, ↑mucosal hyperemia, ↑mucosal necrosis	↑IL-1β, ↑CXCL1, ↑MIP-2, ↑MCP-1, ↑IL-1β mRNA, ↑CXCL1 mRNA, ↑TNF-α mRNA, ↑IL-6 mRNA, ↑NOS2 expression, ↑VEGF expression, ↑Ki67 expression, ↑NF-kB-p65 phosphorylation, ↑ICAM-1 mRNA, ↑VCAM-1 mRNA and ↑LFA-1 mRNA	↓NOS2 expression, ↓VEGF expression and ↓p65 NF-kB activation	[86]
Nobiletin	TNBS-induced Sprague-Dawley rats model of colitis and LPS-induced Caco-2 treated cells	20 and 40 mg/kg/day orally/7 days in vivo and 0, 10, 20, 40, or 80 incubated for 0–36 h µM in vitro	↑DAI, ↓body weight, ↑colon weight-to-length Ratio, ↑intestinal permeability, ↑MPO, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑NO, ↑PGE2, ↑iNOS expression, ↑COX-2 expression in vivo	↑Akt, ↑MLCK mRNA, ↑MLCK protein and ↑NF-kB p65 protein expression in vitro and ↑MLCK, ↑NF-kB, ↑PI3K, ↑Akt and ↑NF-kB p65 protein Expression in vivo	↓Akt, ↓MLCK mRNA, ↓MLCK protein and ↓NF-kB p65 protein expression in vitro and ↓MLCK, ↓NF-kB, ↓phosphatidylinositol 3-kinase (PI3K), ↓Akt, ↓NF-kB p65 protein expression, ↓iNOS expression and ↓COX-2 expression in vivo	[87]
Galangin	DSS-induced Swiss albino mice model of colitis	40 mg/kg/day orally for 20 days	↑Mucosal ulceration, ↑mucosal necrosis, ↑inflammatory cell infiltration in the lamina propria and submucosa	↑TLR4 mRNA, ↑NF-kB p65 nuclear translocation, ↑TNF-α and ↑IL-6	↓TLR4 mRNA, ↓NF-kB-p65 nuclear translocation, ↓TNF-α expression, and ↓IL-6 expression	[88]

↑, increase; ↓, decrease; AcOH, acetic acid; ALP, alkaline phosphatase; Akt, protein kinase b; AP-1, activating protein-1; ASC, apoptosis-associated speck-like protein; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2 protein; BMDMs, bone-marrow-derived macrophages; Caco-2, human colorectal adenocarcinoma cells; CAS, Clinical activity score; CAT, catalase; CD1b, CD1b T cell surface glycoprotein; CD11b, integrin alpha M; CD3, cluster of differentiation 3, c-Fos, cellular proto-oncogene Fos; cl-caspase3, cleaved Caspase-3; CMDI, colon macroscopic damage index; C-MYC, cellular myelocytomatosis oncogene; COX-2, cyclooxygenase 2; CRP, c reactive protein; CXCL-1, chemokine (C-X-C motif) ligand 1; DAI, disease activity index; DMSO, dimethylsulfoxide; DNA, deoxyribonucleic acid; DNCB, dinitrochlorobenzene; DSS, dextran sulfate sodium; ERK, extracellular signal-regulated kinase; GRK2, G-protein-coupled receptor kinase 2; GSK3β, glycogen synthase kinase 3 beta; GSH, glutathione; GSH-Px, glutathione peroxidase; HCT-116, human colorectal carcinoma cell line; HFD, high-fat diet; HO-1, heme oxygenase-1; hPXR, human pregnane X receptor; HT-29, human colorectal adenocarcinoma cell line; ICAM-1, Intercellular Adhesion Molecule 1; ICR, Institute of Cancer Research; IEC-6, intestinal epithelioid cell 6; IFN-γ, interferon gama; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; IKK, multi-subunit IkB kinase; IKKβ, inhibitor of nuclear factor kappa-B kinase subunit beta; IL-1, interleukin 1; IL-1β, interleukin 1 beta; IL-2, interleukin 2; IL-4, interleukin 5; IL-6, interleukin 6; IL-10, interleukin 10; IL-12, interleukin 12; IL-15, interleukin 15; IL-17, interleukin 17; IL-18, interleukin 18; IL-27, interleukin 27; iNOS. inducible nitric oxide synthase; IRAK1, interleukin 1 receptor associated kinase 1; JAM-A, junctional adhesion molecule A; JAK1, Janus kinase 1; JAK2, Janus kinase 2; JNK, c-Jun N-terminal kinases; Ki67, antigen KI-67; KM, Kunming Mouse; LEF-1, lymphoid enhancer binding factor 1; LFA-1, lymphocyte function-associated antigen 1; LDH, lactate dehydrogenase; LPO, lactoperoxidase; LPS, lipopolysaccharide; LRP6, low-density lipoprotein receptor-related protein 6; LTB4, leukotriene B4; Ly6G, lymphocyte antigen 6 complex locus G; MAPK, mitogen-activated protein kinase; MAPK1, mitogen-activated protein kinase 1; MCP-1, monocyte chemoattractant protein-1; MDA, malonaldehyde; MD2, myeloid differentiation protein 2; MDSC, myeloid-derived suppressor cells; MIP-1α, macrophage inflammatory protein 1 α; MIP-2, macrophage inflammatory protein-2; MMP-9, matrix metalloproteinase-9; MLCK, myosin light-chain kinase; MPO, myeloperoxidase; mRNA, messenger RNA; Muc2, Mucin 2, oligomeric mucus/gel-forming; MyD88, MYD88 innate immune signal transduction adaptor; NADPH, nicotinamide adenine dinucleotide phosphate; NF-kB, nuclear factor kappa b; NF-kBp65, NF-kB classical signaling pathway protein; NLRP3, NLR [nucleotide-binding domain leucine-rich repeat] family pyrin domain containing 3; NO, nitric oxide; NOS2, nitric oxide synthase 2 (inducible); Nrf2, nuclear factor erythroid 2–related factor 2; OS, oxidative stress; p-, phosphorylation; p-AKT, phosphorylated protein kinase B; PGD₂/PGE₂, prostaglandin D2; PGE₂, prostaglandin E2; PGJ2, prostaglandin J2; PI3K, phosphoinositide 3-kinase; pNF-kB, phospho-NF-kB p65; PPARγ, peroxisome proliferator- activated receptor gamma; ROS, reactive oxygen species; RSV, resveratrol; SAPK, stress-activated protein kinases; STAMP2, six transmembrane protein of prostate 2; STAT1, signal Transducer And Activator Of Transcription 1; SIRT1, NAD-dependent deacetylase sirtuin-1; SIgA, immunoglobulin A; SIGIRR, single Ig IL-1-related receptor; SOD, superoxide dismutase; STAT3, signal transducer and activator of transcription-3; TAK1, transforming growth factor-β-activated kinase 1; TBARS, thiobarbituric acid reactive substances; TCF-4, transcription factor 4; TDNPs, turmeric-derived nanoparticles; TGF-β, transforming growth factor beta; THP-1, human leukemia monocytic cell line; TLR4, toll-like receptor 4; TLR4-NF-kB-NLRP3, toll-like receptor 4-nuclear factor kappa b-NLR family pyrin domain containing 3; TLR9, toll-like receptor 9; TNBS, 2,4,6-trinitrobenzene sulfonic acid; TNF-α, tumor factor necrosis alfa; TRIF, TIR-domain-containing adapter-inducing interferon-β; VCAM-1, vascular cell adhesion protein 1; VEGF, vascular endothelial growth factor; Wnt-1, proto-oncogene Wnt-1; ZO-1, zonula occludens-1; ZO-2, zonula occludens-2.