https://doi.org/10.4081/jbr.2023.11146
A multicomponent nutraceutical (Perilla frutescens, quercetin, and vitamin D3) as add-on therapy in patients with grass pollen-induced mild persistent asthma and rhinitis
Submitted: January 10, 2023
Accepted: April 5, 2023
Published: May 18, 2023
Accepted: April 5, 2023
Abstract Views: 722
PDF: 154
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Background Allergic asthma is an inflammatory disease characterized by a type 2 immune response. Pollens are a common cause of seasonal asthma. Allergic rhinitis (AR) frequently associates with asthma. The treatment usually aims at controlling inflammation and relieving symptoms. Inhaled corticosteroids are the most effective controller and short-acting b2-agonists (SABA) as a reliever for asthma. Oral antihistamines and nasal corticosteroids (NC) are the mainstays for AR. A multicomponent nutraceutical containing perilla, quercetin, and vitamin D3 significantly prevented AR exacerbations in children. Thus, the current study explored the add-on use in adult patients with mild persistent asthma and AR due to grass pollen allergy.
Methods The treatment lasted three months. Asthma and AR symptoms, asthma control test, spirometry, nasal eosinophils, and use of rescue medications (SABA and NC) were evaluated in the previous grass season and throughout the treatment. All patients were treated with ciclesonide (320 mcg/day) and cetirizine (10 mg/day). Patients were randomly stratified into Group A, taking the nutraceutical, and Group B using the predetermined therapy.
Results 90 patients (13-59 years old) were enrolled, and 84 completed the trial. Group A significantly improved all outcomes (p<0.001). Group B did not achieve an improvement in AR symptoms, nasal eosinophils, and nasal steroid use. The intergroup analysis showed that Group A patients experienced less severe bronchial symptoms (- 32 %), AR symptoms (- 39 %), better asthma control (+ 38 %), higher FEV1 (+ 10 %), lower SABA (- 30 %) and NC use (- 41 %), and nasal eosinophils count (- 35 %) than Group B (p<0.0001 for all).
No clinically relevant adverse events occurred.
Conclusion A multicomponent nutraceutical containing perilla, quercetin, and vitamin D3, as an add-on treatment to inhaled ciclesonide and cetirizine, provided a clinically relevant benefit in patients with mild persistent asthma and AR due to grass pollen uncontrolled by standard therapy.
Global initiative for asthma global strategy for asthma management and prevention (2023). Accessed April 2023. Available from www.ginasthma.org
Taunk ST, Cardet JC, Ledford DK. Clinical implications of asthma endotypes and phenotypes. Allergy Asthma Proc 2022;43:375-82
DOI: https://doi.org/10.2500/aap.2022.43.220047
Kubo M. Innate and adaptive type 2 immunity in lung allergic inflammation. Immunol Rev 2017;278:162-72
DOI: https://doi.org/10.1111/imr.12557
Bousquet J, Hellings PW, Agache I, et al. Allergic rhinitis and its impact on asthma (ARIA) Phase 4 (2018): change management in allergic rhinitis and asthma multimorbidity using mobile technology. J Allergy Clin Immunol 2019;143:864-79
DOI: https://doi.org/10.1016/j.jaci.2018.08.049
Ciprandi G, Cirillo I The lower airway pathology of rhinitis. Update Review. J Allergy Clin Immunol 2006;118:1105-9
DOI: https://doi.org/10.1016/j.jaci.2006.05.010
Busse WW, Kraft M, Rabe KF, et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation. Eur Respir J 2021;58:2003393
DOI: https://doi.org/10.1183/13993003.03393-2020
Bertolini F, Sprio AE, Baroso A, et al. Predictors of low and high exhaled nitric oxide values in asthma: a real-world study. Respiration 2022;101:746-56
DOI: https://doi.org/10.1159/000524498
Indolfi C, Dinardo G, Umano GR, et al. Mometasone furoate nasal spray in Italian children with seasonal allergic rhinitis: a comprehensive assessment. Allergol Immunopathol (Madr) 2022;50:61-7
DOI: https://doi.org/10.15586/aei.v50i5.643
Passalacqua G, Ciprandi G. Pasquali M, et al. An update on the asthma-rhinitis link. Curr Opin Allergy Clin Immunol 2004;4:177-83
DOI: https://doi.org/10.1097/00130832-200406000-00007
Braunstahl GJ, Kleinjan A, Overbeek SE, et al. Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients. Am J Respir Crit Care Med 2000;161:2051–7
DOI: https://doi.org/10.1164/ajrccm.161.6.9906121
Braunstahl GJ, Overbeek SE, Kleinjan A, et al. Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways. J Allergy Clin Immunol 2001;107:469–76
DOI: https://doi.org/10.1067/mai.2001.113046
Papapostolou N, Makris M. Allergic asthma in the era of personalized medicine. J Pers Med 2022;12:1162
DOI: https://doi.org/10.3390/jpm12071162
Usmani OS, Bosnic-Anticevich S, Dekhuijzen R, et al. Real-world impact of nonclinical inhaler regimen switches on asthma or COPD: a systematic review. J Allergy Clin Immunol Pract 2022:10:2624-37
DOI: https://doi.org/10.1016/j.jaip.2022.05.039
Czira A, Turner M, Martin A, et al. A systematic literature review of burden of illness in adults with uncontrolled moderate/severe asthma. Respir Med 2022;191:106670
DOI: https://doi.org/10.1016/j.rmed.2021.106670
Racine G, Forget A, Moullec G, et al. Predictors of asthma control and exacerbations: a real-world study. J Allergy Clin Immunol Pract 2021;9:2802-11.e2
DOI: https://doi.org/10.1016/j.jaip.2021.04.049
Wise SK, Lin SY, Toskala E, et al. International consensus statement on allergy and rhinology: allergic rhinitis. Int Forum Allergy Rhinol 2018;8108-352
DOI: https://doi.org/10.1002/alr.22070
Marseglia GL, Licari A, Ciprandi G. Complementary treatment of allergic rhinoconjunctivitis: the role of the nutraceutical Lertal®. Acta Biomedica 2020;91:97-106
Marseglia GL, Licari A, Ciprandi G. A polycentric, randomized, double blind, parallel-group, placebo-controlled study on Lertal®, a multicomponent nutraceutical, as add-on treatment in children with allergic rhinoconjunctivitis: Phase I during active treatment. J Biol Reg Hom Ag 2019;33:617-22
Marseglia GL, Licari A, Leonardi S, et al. A polycentric, randomized, parallel-group, study on Lertal®, a multicomponent nutraceutical, as preventive treatment in children with allergic rhinoconjunctivitis: Phase II. Ital J Ped 2019;45:84
DOI: https://doi.org/10.1186/s13052-019-0678-y
Zicari AM, De Castro G, Brindisi G, et al. Respiratory infections in allergic children: the preventive role of a multicomponent nutraceutical. Acta Biomedica 2020;91:e2020072
Tosca MA, Olcese R, Marinelli G, et al. Lertal®, a multicomponent nutraceutical, could reduce the use of antihistamines in children with allergic rhinoconjunctivitis. Acta Biomedica 2020;91:356-9
Leonardi S, Parisi G, Papale M, et al. Small airways in children with allergic rhinoconjunctivitis: the potential role of a multicomponent nutraceutical. Acta Biomedica 2020;91:350-5
Nathan RA. Development of the asthma control test: a survey from assessing asthma control. J Allergy Clin Immunol 2004;113:59-65
DOI: https://doi.org/10.1016/j.jaci.2003.09.008
Gelardi M, Fiorella ML, Russo C, et al. Role of nasal cytology. Int J Immunopathol Pharmacol 2010;23:45-9
DOI: https://doi.org/10.1177/03946320100230S112
Stanojevic S, Kaminsky DA, Miller MR, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J 2022;60:2101499
DOI: https://doi.org/10.1183/13993003.01499-2021
Ricca V, Landi M, Ferrero P, et al. Minimal persistent inflammation is present also in patients with seasonal allergic rhinitis. J Allergy Clin Immunol 2000;105:54-7
DOI: https://doi.org/10.1016/S0091-6749(00)90177-5
Shikh EV, Eremenko NN, Arefev KI. Pharmacotherapy of allergic rhinitis: position of a clinical pharmacologist. Vestn Otorinolaringol 2021;86:118-26
DOI: https://doi.org/10.17116/otorino202186031118
Yu H, Qiu JF, Ma LJ, et al. Phytochemical and phytopharmacological review of Perilla frutescens L. (Labiatae), a traditional edible-medicinal herb in China. Food Chem Toxicol 2017;108:375-91
DOI: https://doi.org/10.1016/j.fct.2016.11.023
Makino T, Furuta Y, Wakushima H, et al. Anti-allergic effect of Perilla frutescens and its active constituents. Phytother Res 2003;17:240-3
DOI: https://doi.org/10.1002/ptr.1115
Kamei R, Fujimoura T, Matsuda M, et al. A flavanone derivative from the Asian medicinal herb (Perilla frutescens) potently suppreses IgE-mediated immediate hypersensitivity reactions. Biochem Biphys Res Commun 2017;483:674-9
DOI: https://doi.org/10.1016/j.bbrc.2016.12.083
Igarashi M, Miyazaki Y. A review on bioactivities of Perilla: progress in research on the functions of Perilla as medicine and food. Evid Based Complement Alternat Med 2013;2013:925342
DOI: https://doi.org/10.1155/2013/925342
Kimata M, Shichijo M, Miura T, et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy 2000;30:501-8
DOI: https://doi.org/10.1046/j.1365-2222.2000.00768.x
Theoharides TC, Kempuraj D, Iliopoulou BP. Mast cells, T cells, and inhibition by luteolin: implications for the pathogenesis and treatment of multiple sclerosis. Adv Exp Med Biol 2007;601:423-30
DOI: https://doi.org/10.1007/978-0-387-72005-0_45
Das M, Ram A, Ghosh B. Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflamm Res 2003;52:101-6
DOI: https://doi.org/10.1007/s000110300021
Yano S, Umeda D, Yamashita T, et al. Dietary flavones suppresses IgE and Th2 cytokines in OVA-immunized BALB/c mice. Eur J Nutrition 2007;46:257-63
DOI: https://doi.org/10.1007/s00394-007-0658-7
Shaik YB, Castellani ML, Perrella A, et al. Role of quercetin (a natural herbal compound) in allergy and inflammation. J Biol Regul Homeost Agents 2006;20:47-52
Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and its anti-allergic immune response. Molecules 2016;21,623
DOI: https://doi.org/10.3390/molecules21050623
Kawai M, Hirano T, Arimitsu J, et al. Effect of enzimatically modified isoquercetin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial. Int Arch Allergy Immunol 2009;149:359-68
DOI: https://doi.org/10.1159/000205582
Hirano T, Kawai M, Arimitsu J, et al. Preventative effect of a flavonoid, enzymatically modified isoquercitin on ocular symptoms of Japanese cedar pollinosis. Allergol Intern 2009;58:373-82
DOI: https://doi.org/10.2332/allergolint.08-OA-0070
Muehleisen B, Gallo RL J. Vitamin D in allergic disease: shedding light on a complex problem. J Allergy Clin Immunol 2013;131:324-9
DOI: https://doi.org/10.1016/j.jaci.2012.12.1562
Kim YH, Kim KW, Kim MJ, et al. Vitamin D levels in allergic rhinitis: a systematic review and meta-analysis. Ped Allergy Immunol 2016;27:580-90
DOI: https://doi.org/10.1111/pai.12599
Laird E, McNulty H, Ward M, et al. Vitamin D deficiency is associated with inflammation in older Irish adults. J Clin Endocr Metab 2014;99:1807-15
DOI: https://doi.org/10.1210/jc.2013-3507
Yip KH, Kolesnikoff N, Yu C, et al. Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation. J Allergy Clin Immunol 2014;133:1356-64
DOI: https://doi.org/10.1016/j.jaci.2013.11.030
How to Cite
Marogna, M., & Ciprandi, G. (2023). A multicomponent nutraceutical (<i>Perilla frutescens</i>, quercetin, and vitamin D3) as add-on therapy in patients with grass pollen-induced mild persistent asthma and rhinitis. Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale, 96(1). https://doi.org/10.4081/jbr.2023.11146
Copyright (c) 2023 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.