Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends

Table 1 Overview of the conventional therapies for inflammatory bowel disease

Therapeutic agent	Active compound	Mode of action	Ref.
Aminosalicylates (ASA)	5-ASA	Decreases MPO activity, inhibits β-catenin activation	[23]
		Inhibits the generation and activity of IL-1β, IL-4, IL-5, IL-8, granulocyte-macrophage colony stimulating factor, and TNF-α
Corticosteroids	Corticosteroids		[24]
Immunosuppressants	Azathioprine	Clinical remission	[25]
	6-mercaptopurine	Mucosal healing
	Cyclosporine A
	Tacrolimus
	Methotrexaten
Antibiotics	Metronidazole	Decrease disease activity index	[26]
	Ciprofloxacin	Maintain remission
Biological therapy	Infliximab	Neutralizes TNF-α	[27]
	Adalimumab	Reduces inflammation
	Certolizumab

TNF-α: Tumor necrosis factor α; IL: Interleukin.

Table 2 Role of nutrients and diets against inflammatory bowel disease

Base material	Main compounds/agents	Mode of action	Ref.
Probiotics
Lactic acid bacteria	Lactobacillus suntoryeus	Inhibited the activation of TLR-4-linked NF-κB activation	[32]
	Lactococcus lactis subsp. lactis S-SU2	Prevented the colonic shortening, lowering of liver and thymus weights, and spleen enlargement	[33]
	Lactobacillus paracasei LS2 (from kimchi)	Increased IL-10	[34]
		Reduced TNF-α, IFN-γ, IL-1β and MPO activity
	Lactococcus lactis NZ9000 (NZ-HO)	Reduced CD11b+ F4/80+ and CD11b+ Gr-1+	[35]
	Lactobacillus plantarum AN1	Increased IL-10; reduced IL-1α and IL-6	[36]
	Lactobacillus sakei K040706	Ameliorated the atrophy of colon length, mucosal damage, and spleen enlargement	[38]
Bifidobacteria	Bifidobacterium bifidum 231	Reduced the expression of iNOS, TNF-α, IL-1β, and IL-6	[41]
	Bifidobacterium longum CCM7952	Suppressed NF-κB, STAT3, and TLR4 expression	[31]
		Increased IL-10; Decreased IL-1β
		Engaged TLR2; Contained NOD2
		Improved epithelial barrier
Dietary fibers and prebiotics
Konjac glucomannan	Konjac glucomannan hydrolysate	Reduced bowel movement, diarrhea, blood in feces, abdominal pain, and flatulence	[44]
Glucan	β-(1,3–1,6)-d-glucan	Improved fecal output	[45]
	Oat β-glucan	Reduced visceral pain	[46]
		Lowered MPO, NO, and MDA
		Inhibited the expressions of TNF-α, IL-1β, IL-6 and iNOS
	Glucan from mushroom (Pleurotus pulmonarius)	Reduced histological damage	[47]
	Bacterial β-(1,3)-glucan	Reduced the expression of IL-1β	[48]
		Reversed Treg reduction
Nanofiber	Cellulose nanofiber from seaweed	Decreased NK cell defects and IgA production	[49]
Prebiotics	Cellulose nanofiber from pear	Improved intestinal tissue injury	[50]
		Suppressed the activation of NF-κB
	Fructooligosaccharides	Suppressed colon atrophy	[51]
		Suppressed the activation of NF-κB
	Goat milk oligosaccharide	Decreased IFN-γ, IL-17, and TNF-α levels	[52]
	Inulin	Increased LAB population	[53]
		Decreased inflammation
		Improved mucosal damage
		Decreased TNFα, COX-2, IL-2, and IL-6
Vitamins	1alpha,25-dihydroxyvitamin D3	Suppressed TNF-α	[57]
		Enhanced IL-10 production
	1,25-dihydroxyvitamin D3	Reduced IFN-γ	[58]
	Vitamin D3	Increased CD+ T cells and IL-6	[59]
		Protected mitochondria
	Vitamin A	Inhibited nuclear respiratory factor (NFR)-1 and mitochondrial transcription factor A (TFAM)	[60]

TLR: Toll-like receptor; TNF-α: Tumor necrosis factor α; IFN-γ: Interferon γ; IL: Interleukin; NF-κB: Nuclear factor κB.

Table 3 Role of natural extracts and phytochemicals against inflammatory bowel disease

Base material	Main compound/agent	Mode of action	Ref.
Extracts
Mushroom	Coriolus versicolor extract	Reduced TNF-α, IL-1β and IL-6	[68]
		Reduced STAT1 and STAT6
	Cordiceps militaris extract	Decreased epithelial damage	[70]
		Suppressed iNOS and TNF-α mRNA expression
	Inonotus obliquus extract	Suppressed TNF-α, COX-2, and IFN-γ	[73]
	Ganoderma lucidum extract	Inhibited MAPK phosphorylation and NF-κB activation	[74]
		Decreased histological score
Fruit extracts
Prunus mume	Prunus mume extract	Suppressed mucosal damage, TNF-α, and iNOS expressions	[75]
Pomegranate	Pomegranate extract (ellagitannins and ellagic acid)	Decreased the expression of TNF-α, COX-2, IL-4, and STAT6	[77]
		Prevented the translocation of NF-κB	[78]
Cranberry	Cranberry fruit/extract	Modulated NF-κB and IL-1β signaling	[79]
	Blueberry extract	Attenuated colon shortening
		Suppressed pro-inflammatory cytokines	[80]
Averrhoa bilimbi	Averrhoa bilimbi L. extract	Prevented oxidation
		Inhibited pro-inflammatory mediators	[81]
Aronia melanocarpa	Arronia melanocarpa juice	Reduced NF-κB translocation
Ginger	Ginger extract (zingerone)	Decreased mucosal injury	[82]
Marine food		Decrease the level of pro-inflammatory cytokines	[83]
	Haliotis discus hannai Ino extract	Improved colonic damage	[84]
		Decreased TBARS concentration
		Suppressed NF-κB and IL-1β
	Green algae extract	Suppressed colonic tissue damage
		Downregulated IFN-γ and IL-4
		Ameliorated colonic tissue damage
		Decreased pro-inflammatory cytokines
Phytochemicals	Apple polyphenols	Reduced COX-2 and TNF-α	[85]
		Recovered transglutaminase protein
	Resveratrol	Suppressed NF-κB and TNF-α	[86]
		Reduced clinical score
	Cardamonin	Reduced histopathological damage	[18]
		Reduced iNOS, NF-κB, TNF-α, COX-2, and caspase-3
		Suppressed IL-1β and TNF-α
	Ginsenoside Rg1	Reduced colonic damage and DAI	[90]
		Improved colon shortening and DAI
	Sulforaphane	Suppressed STAT3 expression	[91]
	Curcumin	Reduced TNF-α, IL-1β, and MPO	[92]
		Attenuated morphological damage

TLR: Toll-like receptor; TNF-α: Tumor necrosis factor α; IFN-γ: Interferon γ; IL: Interleukin; NF-κB: Nuclear factor κB.