Table 1.
Preclinical studies regarding the effects of nutraceuticals on the immune system
| Reference | Model | Nutraceutical | Intervention details (duration and oral dose) | Key findings |
|---|---|---|---|---|
| Pasatiempo et al., 1990 | Male Lewis rats | Vitamin A | Vitamin A deficient diet | ·Impaired antibody production against bacterial antigens |
| Cantorna et al., 1995 | B10.BR mice | Vitamin A | Deficient diet, 5 d | ·Increased proinflammatory response (IL-12 and IFN-γ) |
| McDaniel et al., 2015 | C57BL/6 mice | Vitamin A | Vitamin A deficient diet | ·Severe gut infection and increased mortality after exposition to Citrobacter rodentium |
| Qi et al., 2020 | C57BL/6 and ascorbic acid deficient Gulo—/— mice | Vitamin C | − | ·Block of plasma cell differentiation and reduced humoral immune response in deficient mice |
| Ren et al., 2010 | Male young and old C57BL/6 mice | Vitamin E | 6 wk, 500 mg/kg | ·Improved T cell proliferation (old) and IL-1β levels (young) |
| Bendich et al., 1986 | Young rats | Vitamin E | 8~10 wk, 50, 200 mg/kg | ·Improved T and B cell proliferation and responses to mitogens |
| Meydani et al., 1986 | Old mice | Vitamin E | 6 wk, 500 mg/kg | ·Increased lymphocyte proliferation and IL-2 levels |
| Wakikawa et al., 1999 | Young and old C57BL/6 mice | Vitamin E | 9 wk, 500 IU (500 mg) | ·Increased lymphocyte proliferation and IFN-γ levels (young) |
| Moriguchi et al., 1990 | Male F344 rats | Vitamin E | 7 d, 50, 100, 250, 500, 2,500 mg/kg | ·Increased lymphocyte proliferation and NK activity |
| Tanaka et al., 1979 | SL mice | Vitamin E | 6~12 wk, 200 mg/kg | ·Increased antibody response |
| Beherka et al., 2000 | C57BL/6NCrlBR mice | Vitamin E | 6 mon, 500 mg/kg | ·Reduced IL-6 levels and NOS production by macrophages |
| Han et al., 2000 | C57BL/6 mice | Vitamin E | 8 wk, 500 mg/kg | ·Reduced influenza titer ·Increased IL-2 and IFN-γ production |
| Hayek et al., 1997 | C57BL/6NIA mice | Vitamin E | 6 wk, 500 mg/kg | ·Reduced influenza A/PC/1/73 (H3N2) titer |
| Tvedten et al., 1973 | Sprague-Dawley rats | Vitamin E + Vitamin A | 6 wk, 180 mg/kg diet + 6,000 IU vitamin A | ·Increased Mycoplasma pulmonis resistance to infection |
| Malpuech-Brugère et al., 2000 | Male Winstar rats | Magnesium | 4~8 d, Mg deficient diet | ·Increased IL-6 levels ·Increased macrophages number and activity |
| Bhaumik et al., 2000 | Winstar rats | Curcumin | 20 d, 20 mg/d (intraperitoneal injection) | ·Increased NO production by NK cells |
| Exon et al., 1998 | Female Sprague-Dawley rats | Quercetin | 7 wk, 100 mg/kg | ·Increased NK cells activity |
| Ahmad et al., 2013 | BALB/c mice | Proanthocyanidin | Grape seed proanthocyanidin extract, 14 d, 25, 50, or 100 mg/kg | ·Upregulation of Treg cells ·Reduction of inflammatory mediators’ levels |
| Lin et al., 2014 | Male BALB/c mice | Sesamin | 6 d, 1 mg/kg, 10 mg/kg, and 20 mg/kg (intraperitoneal injection) | ·Decreased expression levels of IL-4, IL-5, IL-13, and serum IgE ·Reduced total inflammatory cells and eosinophils |
| Morinobu et al., 2008 | Male DBA/1 mice | EGCG | 15 d, 20 μg/g/d (intraperitoneal injection) | ·Ameliorated arthritis during disease course |
| Gonçalves et al., 2017 | Male Holtzman rats | Grape polyphenols | Merlot grape pomace extract, 23 d, 250 mg/kg/d | ·Normal oxidative stress indicators (GSH, GSGG, GSH/GSGG) |
| Stamer et al., 2017 | Female TNF transgenic mice | Grape polyphenols | Grape powder, 4 wk, 50~100 g/kg/d | ·Decreased inflammation induced formation of synovitis/enthesitis ·Downregulated TNF-mediated enhancement in transcript levels of cytokines (TNF and IL-1β), RANKL, MMP1&3, and CCL3/MIP1α |
| Lee et al., 2009 | Female BALB/c mice | Resveratrol | 32 d, 30 mg/kg (nebulization on days 28, 29, and 30) | ·Decrease of IL-4 and IL-5 in plasma and bronchoalveolar lavage fluid ·Suppression of airway hyperresponsiveness, eosinophilia, and mucus hypersecretion |
| Ravikumar and Kavitha, 2020 | Adult male BALB/c mice | Resveratrol | 12 d, 10~30 mg/kg | ·Decreased number of eosinophils and IL-4 levels ·Reduced the allergic airway inflammation by inhibiting inflammatory cell infiltration and mucous cell metaplasia ·Significant glucose reduction |
| Bae et al., 2015 | Male C57BL/6 mice | Kazinol C and isokazinol D | 3 d, 10 mg/kg (intraperitoneal injection) | ·Prevention of cytokine-induced β-cell damage |
| Khalaf et al., 2019 | Mature albino rats | Phytocompounds from Echinacea purpurea | Herbal formulation containing E. purpurea extract, 2 wk, 250 mg/kg | ·Increased activation of activating neutrophils, macrophages, and NK cells |
| Park et al., 2021 | C57BL/6N mice | Phytocompounds from E. purpurea | 2 wk, 50, 100, and 200 mg/kg | ·Increased NK cell activity, MHC II, CD4+ T cells, Th1 cytokines, and B-cell proliferation |
| Lewicki et al., 2017 | Pregnant BALB/c mice | Phytocompounds from Rhodiola kirilowii | R. kirilowii aqueous or 50% hydroalcoholic extracts, 28 d, 20 mg/kg/d | ·Increased percentage of granulocytes ·Decreased percentage of lymphocytes ·Stimulation of granulocyte phagocytosis |
IL, interleukin; IFN-γ, interferon-γ; NET, neutrophil extracellular trap; NK, natural killer; NOS, nitric oxide synthase; NO, nitric oxide; Treg, regulatory T cell; IgE, immunoglobulin E; GSH, reduced glutathione; GSGG, oxidized glutathione; TNF, tumor necrosis factor; RANKL, receptor activator of nuclear factor-κB ligand; MMP, matrix metalloproteinase; CCL3/MIP-1α, chemokine C-C ligand 3/macrophage inflammatory protein-1α; MHC II, major histocompatibility complex class II; CD, cluster of differentiation; Th1, T-helper 1 cells.