Background: Flavonoids exert antiallergic and antioxidant effects. We investigated the efficacy of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve symptoms of pollinosis. Methods: In a parallel-group, double-blind placebo-controlled study design, 20 subjects with Japanese cedar pollinosis took two capsules daily of 100 mg EMIQ or a placebo for 8 weeks during the pollen season. Subjective symptoms and activities of daily living (ADL) scores were recorded every day, and the quality of life (QOL) score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum cytokines, chemokines, IgE, quercetin and oxidized biomarkers. Results: During the entire study period, total ocular score and ocular itching score for the EMIQ group were significantly lower (p < 0.05) than for the placebo group. When limited to the individual periods, total symptom score for the EMIQ group was significantly lower (p < 0.05, week 4–5) than that for the placebo group while other scores for the EMIQ group, such as total nasal score (p = 0.06, week 4–5), nasal obstruction score (p = 0.08, week 4–5), lacrimation score (p = 0.06, week 5–6), ocular congestion score (p = 0.08, week 4–7) and ADL score (p = 0.08, week 4–7), all tended to be lower. The levels of serum cytokines such as interleukin (IL)-4, IL-5, IL-12, IL-13, interferon-γ, and eotaxin and IgE were not significantly downregulated by the intake of EMIQ but the serum concentrations of oxidized low-density lipoprotein and thymus and activation-regulated chemokine were reduced. Conclusion: Intake of the quercetin glycoside EMIQ was safe and influenced ocular symptoms caused by pollinosis.

1.
Holgate ST: The epidemic of allergy and asthma. Nature 1999;402:B2–B4.
2.
Eder W, Ege MJ, von Mutius E: The asthma epidemic. N Engl J Med 2006;355:2226–2235.
3.
Horiguchi S, Saito Y: Discovery of Japanese cedar pollinosis in Nikko, Ibaraki prefecture. Arerugi 1964;13:16–18.
4.
Kaneko Y, Motohashi Y, Nakamura H, Endo T, Eboshiba A: Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis. Int Arch Allergy Immunol 2005;136:365–371.
5.
Nolte H, Backer V, Porsbjerg C: Environmental factors as a cause for the increase in allergic disease. Ann Allergy Asthma Immunol 2001;87:S7–S11.
6.
McKeever TM, Britton J: Diet and asthma. Am J Respir Crit Care Med 2004;170:725–729.
7.
Devereux G, Seaton A: Diet as a risk factor for atopy and asthma. J Allergy Clin Immunol 2005;115:1109–1117.
8.
Devereux G: The increase in the prevalence of asthma and allergy: food for thought. Nat Rev Immunol 2006;6:869–874.
9.
Tricon S, Willers S, Smit HA, Burney PG, Devereux G, Frew AJ, Halken S, Host A, Nelson M, Shaheen S, Warner JO, Calder PC: Nutrition and allergic disease. Clin Exp Allergy Rev 2006;6:117–188.
10.
Harborne JB, Williams CA: Advance in flavonoid research since 1992. Phytochemistry 2000;55:481–504.
11.
Fewtrell CM, Gomperts BD: Effect of flavone inhibitors on transport ATPases on histamine release. Nature 1977;265:635–636.
12.
Middleton EJ, Kandaswami C: Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol 1992;43:1167–1179.
13.
Higa S, Hirano T, Kotani M, Matsumoto M, Fujita A, Suemura M, Kawase I, Tanaka T: Fisetin, a flavonol, inhibits T helper 2 (Th2) type cytokine production by activated human basophils. J Allergy Clin Immunol 2003;111:1299–1306.
14.
Hirano T, Higa S, Arimitsu J, Naka T, Shima Y, Ohshima S, Fujimoto M, Yamadori T, Kawase I, Tanaka T: Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils. Int Arch Allergy Immunol 2004;134:135–140.
15.
Hirano T, Arimitsu J, Higa S, Naka T, Ogata A, Shima Y, Fujimoto M, Yamadori T, Ohkawara T, Kuwahara Y, Kawai M, Kawase I, Tanaka T: Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human basophils. Int Arch Allergy Immunol 2006;140:150–156.
16.
Kotani M, Matsumoto M, Fujita A, Higa S, Wang W, Suemura M, Kishimoto T, Tanaka T: Persimmon leaf extract and astragalin inhibit development of dermatitis and IgE elevation in NC/Nga mice. J Allergy Clin Immunol 2000;106:159–166.
17.
Matsumoto M, Kotani M, Fujita A, Higa S, Kishimoto T, Suemura M, Tanaka T: Oral administration of persimmon leaf extract ameliorates skin symptoms and transepidermal water loss in atopic dermatitis model mice, NC/Nga. Br J Dermatol 2002;146:221–227.
18.
Tanaka T, Higa S, Hirano T, Kotani M, Matsumoto M, Fujita A, Kawase I: Flavonoids as potential anti-allergic substances. Curr Med Chem Anti-Inflammtory Anti-Allergy Agents 2003;2:57–65.
19.
Tanaka T, Higa S, Hirano T, Arimitsu J, Naka T, Shima Y, Ohshima S, Fujimoto M, Yamadori T, Kawase I: Is an appropriate intake of flavonoids a prophylactic means or complementary and alternative medicine for allergic diseases? Recent Res Dev Allergy Clin Immunol 2004;5:1–14.
20.
Kawai M, Hirano T, Higa S, Arimitsu J, Maruta M, Kuwahara Y, Ohkawara T, Hagihara K, Yamadori T, Shima Y, Ogata A, Kawase I, Tanaka T: Flavonoids and related compounds as anti-allergic substances. Allergol Int 2007;56:113–123.
21.
Japan’s Specifications and Standards for Food Additives, ed 8, 2007, pp 346–347.
22.
Salim EI, Kaneko M, Wanibuchi H, Morimura K, Fukushima S: Lack of carcinogenicity of enzymatically modified isoquercitrin in F344/DuCrj rats. Food Chem Toxicol 2004;42:1949–1969.
23.
Baba K, Konno A, Takenaka H: Epidemiology; in Okuda M (ed): Guidelines for Treatment of Nasal Allergy-Perennial Rhinitis and Pollinosis. Tokyo, Lie Science Publishing, 2002, pp 8–11.
24.
Okuda M, Ohkubo K, Goto M, Okamoto Y, Konno A, Baba K: Japanese allergic rhinitis quality of life questionnaire. Jpn J Allergol 2003;52(suppl 1):21–56.
25.
Radtke J, Linseisen J, Wolfram G: Fasting plasma concentrations of selected flavonoids as markers of their ordinary dietary intake. Eur J Nutr 2002;41:203–209.
26.
Benzie IF, Strain JJ: The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay. Anal Biochem 1996;239:70–76.
27.
Kerr JR, Cunniffe VS, Kelleher O, Coats AJ, Mattey DL: Circulating cytokines and chemokines in acute symptomatic parvovirus B18 infection: negative association between levels of pro-inflammatory cytokines and development of B19-associated arthritis. J Med Virol 2004;74:147–155.
28.
Yoshimura M, Enomoto T, Dake Y, Okuno Y, Ikeda H, Cheng L, Obata A: An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis. Allergol Int 2007;56:225–230.
29.
Segawa S, Takata Y, Wakita Y, Kaneko T, Kaneda H, Watari J, Enomoto T, Enomoto T: Clinical effects of a hop water extract on Japanese cedar pollinosis during the pollen season: a double-blind, placebo-controlled trial. Biosci Biotechnol Biochem 2007;71:1955–1962.
30.
Williams RJ, Spencer JPE, Rice-Evans C: Flavonoids: antioxidants or signaling molecules? Free Radic Biol Med 2002;36:838–849.
31.
Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N, Nagai H: Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy 2000;30:501–508.
32.
Das M, Ram A, Ghosh B: Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflamm Res 2003;52:101–106.
33.
Ko WC, Shih CM, Chen MC, Lai YH, Chen JH, Chen CM, Lin CM: Suppressive effects of 3-O-methylquercetin on ovalbumin-induced airway hyperresponsiveness. Planta Med 2004;70:1123–1127.
34.
Wu YQ, Zhou CH, Tao J, Li SN: Antagonistic effects of nobiletin, a polymethoxyflavonoid, on eosinophillic airway inflammation of asthmatic rats and relevant mechanisms. Life Sci 2006;78:2689–2696.
35.
Rogerio AP, Kanashiro A, Fontanari C, da Silva EVG, Lucisano-Valim YM, Soares EG, Faccioli LH: Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma. Inflamm Res 2007;56:402–408.
36.
Jung CH, Lee JY, Cho CH, Kim CJ: Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin. Arch Pharm Res 2007;30:1599–1607.
37.
Funaguchi N, Ohno Y, La BLB, Asai T, Yuhgetsu H, Sawada M, Takemura G, Minatoguchi S, Fujiwara T, Fujiwara H: Narirutin inhibits airway inflammation in an allergic mouse model. Clin Exp Pharmacol Physiol 2007;34:766–770.
38.
Xiao JZ, Kondo S, Takahashi N, Odamaki T, Iwabuchi N, Miyaji K, Iwatsuki K, Enomoto T: Changes in plasma TARC levels during Japanese cedar pollen season and relationships with symptom development. Int Arch Allergy Immunol 2007;144:123–127.
39.
Okamoto T, Yoshida O: Constituents of Pollen. XI. Constituents of Cryptomeria japonica D. Don.Chem Pharm Bull (Tokyo) 1983;31:919–924.
40.
Morimoto Y, Yasuhara T, Sugimoto A, Inoue I, Hide I, Akiyama M, Nakata Y: Anti-allergic substances contained in the pollen of Cryptomeria japonica possess diverse effects on the degranulation of RBL-2H3 cells. J Pharmacol Sci 2003;92:291–295.
41.
Ishida Y, Nakamura F, Kanzato H, Sawada D, Yamamoto N, Kagata H, Ohida M, Takeuchi H, Fujiwara S: Effect of milk fermented with Lactobacillus acidophilus strain L-92 on symptoms of Japanese cedar pollen allergy: a randomized placebo-controlled trial. Biosci Biotechnol Biochem 2005;69:1652–1660.
42.
Kishi K, Saito M, Saito T, Kumemura M, Okamatsu H, Okita M, Takazawa K: Clinical efficacy of apple polyphenol for treating cedar pollinosis. Biosci Biotechnol Biochem 2005;69:829–832.
43.
Xiao JZ, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N, Miyaji K, Iwatsuki K, Togashi H, Enomoto K, Enomoto T: Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial. Clin Exp Allergy 2006;36:1425–1435.
44.
Knekt P, Kumpulainen J, Jarvinen R, Rissanen H, Heliovaara M, Reunanen A, Hakulinen T, Aromaa A: Flavonoids intake and risk of chronic diseases. Am J Clin Nutr 2002;76:560–568.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.