Dietary intake of flavonoids and asthma in adults

Garcia, V.; Arts, Ilja C. W.; Sterne, Jonathan A C; Thompson, Rachel; Shaheen, Seif O.

doi:10.1183/09031936.05.00142104

Cited by 60 publications

(46 citation statements)

References 27 publications

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“…31) Naturally occurring flavonoids with safety have attracted considerable attention as anti-allergic agents 5) suppressing Th2 cytokine production in T cells 32) as well as basophils, 33) and intake of flavonoids has been known to reduce the incidence and severity of allergies in humans. 5,6) In this study we showed that 25 mM of T-412 almost completely inhibited IL-4 production in activated T cells without affecting cell viability. T-412 suppressed the IL-4 expression at the transcriptional level, and we found that T-412 could control the selective transcription factors including NF-AT/AP-1 and c-Maf but not NF-kB.…”

Section: Discussionmentioning

confidence: 79%

Suppressive Effects of T-412, a Flavone on Interleukin-4 Production in T Cells

Jin

Park

Pyo

2009

Biological & Pharmaceutical Bulletin

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Flavonoids are comprised of a large group of low molecular weight polyphenolic compounds having diverse pharmacological effects, 1,2) and among them their possible use as anti-allergic agents have been proposed. [3][4][5] Intakes of naturally occurring flavonoids have been reported to reduce the allergic symptoms and severities in human 6) as well as development of allergic diseases in animals, 7) and it was suggested that the effects might be mediated by the suppression of immune responses caused by Th2 dominance. 5-7)Interleukin (IL)-4 is a representative Th2 cytokine, which is mainly produced by activated Th2 cells. IL-4 not only initiates the development of Th2 cells from Th0 cells but also induces IgE class switching in B cells, resulting in unbalanced Th2 skewing immune system. 8) Furthermore, it plays a central role in the pathogenesis of various allergic inflammations by promoting production of proinflammatory cytokines such as 10) The expression of IL-4 is tightly regulated at the transcriptional level. The inducible transcription factors including nuclear factor of activated T cells (NF-AT), activating protein-1 (AP-1), nuclear factor-kappa B (NF-kB) as well as c-Maf have been identified to control IL-4 and their cooperative interactions on the promoter appears to be critical to induce IL-4 expression in T cells.11,12) Upon T cell activation by PMA and ionomycin (PI), cytoplasmic NF-ATs are dephosphorylated and translocated to the nucleus; the dephosphorylated proteins show increased affinity for P sites (from P0-P4), DNA binding sites of NF-ATs, [13][14][15] which is mediated by increased calcium concentration and protein kinase C (PKC)-RAS signaling pathways.16) NF-AT and AP-1 protein (c-Fos and c-Jun) coordinately bind the P1 site, which is required for full activity of the IL-4 promoter.17-19) NF-kB, generally consisting of p65-p50 dimer, is sequestered into an inactive form by the cytoplasmic inhibitor of NF-kB (IkB) in resting T cells, however active forms of NF-kB translocate to nucleus, where the IL-4 expression is regulated together with other transcription factors.20) Furthermore, the proto-oncogene c-Maf, which is expressed in Th2 cells but not in Th1 cells, binds to a c-Maf response element (MARE) adjacent to a P0 site in synergy with the NF-AT to activate IL-4 production. 21,22)As an effort to find out novel therapeutics from natural sources we screened the down-regulatory effects of several novel flavonoids on IL-4 using PI-activated EL-4 thymoma, a murine T cell line. Among them a flavone, named T-412 (7,8,4Ј-trihydroxyflavone), had significant down-regulatory effects on IL-4 production in a dose-and time-dependent manner, which was accompanied by the suppression of the expression level of IL-4 mRNA. Furthermore, the proximal promoter activities of IL-4 were also suppressed. To understand the mode of action for T-412 at the molecular level when we performed Western blot analysis for selective transcription factors involving in the activation of proximal promoter, the expression of NF-ATc...

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Section: Discussionmentioning

confidence: 79%

Suppressive Effects of T-412, a Flavone on Interleukin-4 Production in T Cells

Jin

Park

Pyo

2009

Biological & Pharmaceutical Bulletin

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“…Kotani et al [2000] reported that oral administration of flavonoids such as astragalin and kaemperol suppresses the onset of allergic disease in the atopic dermatitis of NC/Nga mice, and that the intake of flavonoids in asthmatic models leads to a significant suppression of symptoms including bronchial hyperactivity and bronchoconstriction. Intake of human traditional vegetarian diet containing flavonoids has been reported to reduce symptoms of atopic dermatitis [Knekt et al, 2002;Garcia et al, 2005]. Although fisetin has suppressive effects on Th2 cytokines in human basophils [Higa et al, 2003], its molecular mechanisms for the suppression of Th2 cytokine production in basophils and mast cells has been incompletely elucidated.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of T helper 2-associated cytokine expression and selective transcription factors by fisetin

Jin

Yoon

Pyo

2011

J Korean Soc Appl Biol Chem

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Fisetin, a flavonol, has been known as an anti-allergic agent having inhibitory effects on T helper 2 cytokine gene expression in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on interleukin (IL)-4 and IL-13 in activated mast cells and basophils have been incompletely understood. In this study we found that fisetin at the concentrations having no effect on cell viability significantly inhibited the phorbol 12-myristate 13-acetate and ionomycin induced production of IL-4 and IL-13 in bone marrow-derived mast cells and RBL-2H3 basophilic cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Transient transfection experiments using luciferase reporter plasmids expressing IL-4 or IL-13 promoter revealed that fisetin inhibited the activation of the promoters in a dose-dependent manner. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppressions of cFos and CCAAT/enhancer-binding protein alpha were prominent together with significant downregulations of nuclear factor of activated T cell (NF-AT) and NF-κB. Furthermore, nuclear expression of GATA-1 and GATA-2, and the mRNA expression were significantly down regulated by fisetin, whereas cyclosporine A had no significant effects on GATA transcription factors. Taken together, fisetin has suppressive effects on IL-4 and IL-13 gene expressions through the regulation of selective transcription factors.

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“…In studies using Western diets (9,11,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48), mean intakes from the various classes of flavonoids were about 10 mg/day for anthocyanins, 84 mg/day for flavan-3-ols, 33 mg/d for flavanones, 0.5 mg/d for flavones, 17 mg/day for flavonols, 6 mg/day for isoflavones, and 170 mg/day for total flavonoids. The women in the WINS population tended to have higher mean intakes compared to these other populations of flavan-3-ols, flavones, flavonols and lower for flavanones, perhaps because we used more complete data than were available to these earlier investigators or because we included flavonoid-containing supplements.…”

Section: Flavonoid Intakesmentioning

confidence: 98%

Do Flavonoid Intakes of Postmenopausal Women With Breast Cancer Vary on Very Low Fat Diets?

Dwyer

Peterson

Winters

et al. 2008

Nutrition and Cancer

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In the Women's Intervention Nutrition Study (WINS), a very low-fat eating pattern decreased breast cancer recurrence. We assessed whether the women's flavonoid intakes varied on the very low fat diet. A total of 550 randomly selected WINS participants who had been treated with conventional therapy (surgery, chemotherapy, and/or radiation) for primary breast cancer were randomized to either a very low fat diet (15% of calories from fat, N = 218) or their usual diets (30% calories from fat, N = 332). We compared their intakes of total flavonoids and 6 flavonoid classes (isoflavones, flavones, flavanones, flavonols, flavan-3-ols, and anthocyanins) for these 2 groups using the U.S. Department of Agriculture food flavonoid database and a flavonoid dietary supplement database on three 24-h dietary recalls at baseline and 12 mo after randomization. At baseline, neither mean fat intakes (31.7% +/- 6.8 SD of calories, n = 332 in the usual diet group and 31.6% +/- 6.8 SD of calories, n = 218 in the very low fat diet group; P = NS) nor flavonoid intakes (218 +/- 283 SD mg/day, n = 332 in the usual diet group and 236 +/- 393 SD mg/day, n = 218 in the very low fat diet group; P = NS) differed. Over half of the women's flavonoid intakes were from the flavan-3-ols. After 12 months of intervention, with 39 participants lost to follow-up, dietary fat intakes were 30.7 +/- 8.4 SD calories (n = 316) among those on their usual diets but were significantly lower among those on the very low fat diet intervention: 21.4 +/- 8.3 SD calories (n = 195), P = <0.05. However, flavonoid intakes remained similar in both groups (201 +/- 252 SD mg/day, n = 316 in the usual diet group vs. 235 +/- 425 SD mg/day, n = 195 in the very low fat group; P = NS). In this random sample of WINS participants, neither total flavonoid intakes nor intakes of subclasses of flavonoids differed between those who had dramatically decreased their fat intakes and those who had not. Flavonoid intakes are therefore unlikely to account for WINS results on differences between the groups in cancer recurrence.

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Dietary intake of flavonoids and asthma in adults

Cited by 60 publications

References 27 publications

Suppressive Effects of T-412, a Flavone on Interleukin-4 Production in T Cells

Suppressive Effects of T-412, a Flavone on Interleukin-4 Production in T Cells

Down-regulation of T helper 2-associated cytokine expression and selective transcription factors by fisetin

Do Flavonoid Intakes of Postmenopausal Women With Breast Cancer Vary on Very Low Fat Diets?

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