. 2019 Jun 27;11(7):1464. doi: 10.3390/nu11071464

Table 3.

Nonexclusive listing of studies on the effects of citrus flavanones on host parameters related to barrier function and inflammation.

Model [Ref.]	Treatment	Treatment Duration	Dose and Administration	Change in Main Outcomes vs. Control (Relevant Concentrations)
Caco-2 cell monolayers [73]	Hesperetin vs. control Naringenin vs. control	24 h	100 µM	Barrier function: $↑$ TEER, occludin expression, claudin-4 expression, cytoskeletal association of occludin and claudin-1, and -3 $\leftrightarrow$ FITC–dextran flux Barrier function: $↑$ TEER, occludin expression, claudin-4 expression, cytoskeletal association of ZO-2, occludin and claudin-1, -3, and -4 $\leftrightarrow$ FITC–dextran flux
Caco-2 cell monolayers [74]	Naringenin vs. control	48 h	10, 30, 100 µM	Barrier function: $↑$ TEER (30, 100 µM)†, claudin-4 expression (30, 100 µM)†, cytoskeletal association of occludin, claudin-1, claudin-4 and ZO-2 (100 µM) $↓$ FITC–dextran flux (30, 100 µM)†
DSS-induced colitis in male BALB/c mice [76]	Naringenin vs. control diet	9 days	0.3% of the diet, oral administration	Barrier function: $↓$ Colonic permeability, claudin-1 expression $↑$ Occludin, junctional adhesion molecule-A, claudin-3 expression Inflammation: $↓$ DAI, colonic shortening, expression of cytokines (IFN-ϒ, IL-6, MIP-2, and IL-17A)
DSS-induced colitis in male BALB/c mice [77]	Naringenin vs. control diet Hesperetin vs. control diet	12 days	0.3% of the diet, oral administration 0.3% of the diet, oral administration	Barrier function: $↓$ Colonic permeability $↑$ Occludin expression Inflammation: $↓$ Weight loss, colonic damage $↑$ Colon length Barrier function: $\leftrightarrow$ Colonic permeability, occludin expression Inflammation: $↓$ Weight loss, colonic damage $\leftrightarrow$ Colon length
DSS-induced colitis in male BALB/c mice [78]	Hesperidin vs. control	7 days	10, 40, 80 mg/kg, oral administration	Inflammation: $↓$ DAI, MPO, MDA, IL-6, colonic wet weight (10, 40, 80 mg/kg)† $↓$ Mucosal cell damage (80 mg/kg) $\leftrightarrow$ IL-4 (10, 40, 80 mg/kg)
TNBS-induced colitis in female Wistar rats [79]	Hesperidin vs. control	Twice (48 h pre- + 48 h post-colitis induction)	2.5, 5, 10, 25, 50 mg/kg, oral administration	Inflammation: $↓$ Colonic damage, colonic weight, colonic MPO (10, 25 mg/kg) $↑$ Glutathione levels (10, 25 mg/kg), colonic fluid absorption (10–50 mg/kg) $\leftrightarrow$ MDA, LTB4 (2.5–50 mg/kg)
TNBS- induced colitis in male Wistar rats [80]	Orange juice vs. control Grapefruit juice vs. control Combination vs. control	15 days	2 mL/kg, 5 mL/kg, 8 mL/kg, oral administration 0.1 mL/kg, 0.3 mL/kg, 0.5 mL/kg, oral administration 2 mL/kg OJ + 0.1 mL/kg GJ (low dose), 5 mL/kg OJ + 0.3 mL/kg GJ (high dose), oral administration	Inflammation: $↓$ Colonic damage (2, 5, 8 mL/kg), MPO, CRP (5, 8 mL/kg), ALP (8 mg/kg) $↑$ GSH (8 mL/kg) Inflammation: $↓$ Colonic damage (0.1, 0.3, 0.5 mL/kg) MPO, CRP (0.3, 0.5 mL/kg), ALP (0.3, 0.5 mL/kg) $↑$ GSH (0.3 mL/kg) Inflammation: $↓$ Colonic damage, MPO, CRP, ALP (low dose, high dose) $↑$ GSH (high dose)
DNBS- induced colitis in Male CD1 mice [81]	Bergamot juice extract vs. control	4 days	5, 10, 20 mg/kg, oral administration	Inflammation: $↓$ Colonic damage, weight loss, MPO, TNF-α, IL-1β, ICAM-1, p-selectin, nitrotyrosine, PAR, nuclear NF-kB translocation, p-JNK activation (20 mg/kg) $↑$ Colon length (20 mg/kg)
LPS-challenged broiler chickens [82]	Hesperidin vs. control diet	42 days	20 mg/kg diet, oral administration	Inflammation: $↑$ Phagocytic index, villus length, villus width, villus length/crypt depth $↓$ Crypt depth $\leftrightarrow$ Body weight gain, feed intake feed conversion ratio
Human subjects with features of metabolic syndrome [68]	Citrus extract (>80% hesperidin-2S and <4% of naringin) vs. placebo	12 weeks	500 mg, oral administration	Inflammation: $\leftrightarrow$ Calprotectin

TEER, transepithelial electrical resistance. FITC, fluorescein isothiocyanate. ZO-2, zonula occludens 2. DSS, dextran sulfate sodium. DAI, disease activity index. IFN-ϒ, interferon-ϒ. IL, interleukin. MIP-2, macrophage inflammatory protein-2. MPO, myeloperoxidase. MDA, malondialdehyde. TNBS, trinitrobenzene sulfonic acid. LBT4, leukotriene B4. OJ, orange juice. GJ, grapefruit juice. CRP, C-reactive protein. ALP, alkaline phosphatase. GSH, glutathione. DNBS, dinitrobenzene sulfonic acid. TNF-α, tumor necrosis factor-α. ICAM-1, intercellular adhesion molecule-1. PAR, poly ADP-ribose. NF-kB, nuclear factor-kB. $↑$ , increase. $↓$ , decrease. $\leftrightarrow$ , no significant change. †, dose-dependent effect.