Complementary treatment of allergic rhinoconjunctivitis: the role of the nutraceutical Lertal(R)
Keywords:
allergic rhinoconjunctivitis, nutraceuticals, quercetin, perilla, vitamin D3Abstract
Nutraceuticals represent interesting therapeutic options in clinical practice. In this regard, a new compound has been designed: Lertal®. It contains quercetin, perilla extract, and vitamin D3. These agents exert anti-allergic and anti-inflammatory activities. This article reports and discusses the results of four clinical studies conducted in adult and paediatric patients suffering from AR. Outcomes provided evidence that Lertal® may significantly prevent clinical worsening when prescribed as add-on to continuous antihistaminic treatment and also prevent clinical exacerbations, such as the need of rescue medication, when used alone as preventive strategy in AR patients.
References
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3) Imaoka K, Inouye S, Takahashi et al. Effects of Perilla frutescens extract on anti-DNP IgE antibody production in mice. Arerugi. 1993;42(1):74-80.
4) Ueda H, Yamazaki C, Yamazaki M. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. . Biol Pharm Bull. 2002;25(9):1197-202
5) Makino T, Furuta Y, Wakushima H et al. Anti-allergic effect of Perilla frutescens and its active constituents. Phytother Res. 2003;17(3):240-3
6) 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 ResCommun 2017;483:674-9
7) 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
8) Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N and Nagai H. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clinical and Experimental Allergy. 2000;30:501-508
9) Theoharides TC, Kempuraj D and 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
10) Das M, Ram A and Ghosh B. Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflammation Research. 2003;52:101-106
11) Yano S, Umeda D, Yamashita T, Ninomiya T, Sumida M, Fujimura Y, Yamada K and Tachibana H. Dietary flavones suppresses IgE and Th2 cytokines in OVA-immunized BALB/c mice. European Journal of Nutrition. 2007;46:257-263
12) 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(3-4):47-52
13) Chirumbolo S. The role of Quercetin, Flavonols and Flavones in modulating inflammatory cell function. Inflamm Allergy-Drug Targets 2010; 9(4):263-85
14) Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and its anti-allergic immune response. Molecules 2016;21,623
15) Kawai M, Hirano T, Arimitsu J, et al. Effect of enzimatically modified isoquercetitrin, a flavonoid, on symptoms of Japanes cedar pollinosis: a rando,ized double-blind placebo-controlled trial. Int Arch Allergy Immunol 2009;149:359-68
16) Hirano T, Kawai M, Arimitsu J, et al. Preventative effect of a flavomnoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis Allergol Intern 2009;58:373-82
17) Ebibara N, Takahashi K, Takemura H, et al. Suppressive effect of quercetin on nitric oxide production from nasal epithelial cells in vitro. Evidence-based Complement Altern Medicine 2018;ID 6097625
18) Sakai-Kashiwabara M, Asano K. Inhibitory action of quercetin on eosinophil activation in vitro. Evidence-based Complement Altern Medicine 2013;ID 127105
19) Muehleisen B, Gallo RL J. Vitamin D in allergic disease: shedding light on a complex problem Allergy Clin Immunol. 2013;131(2):324-9
20) Bozzetto S, Carraro S, Giordano G et al. Asthma, allergy and respiratory infections: the vitamin D hypothesis. Allergy. 2012 ;67(1):10-7
21) Yepes-Nunes JJ, Brozek JL, Fiocchi A, Pawankar R, Cuello-Garcia C, Zhang Y, et al. Vitamin D supplementation in primary allergy prevention: systematic review of randomized and non-randomized studies. Allergy 2018;73:37-49
22) Kim YH, Kim KW, Kim MJ, Sol IS, Yoon SH, Ahn HS, et al. Vitamin D levels in allergic rhinitis: a systematic review and meta-analysis. Ped Allergy Immunol 2016;27:580-90
23) Aryan Z, Rezaei N, Camargo CA. Vitamin status, aeroallergen sensitization, and allergic rhinitis: a systematic review and meta-analysis. Int Rev Immunol 2017;36:41-53
24) Loo EXL, Tham EH, Phang KW, Goh A, Teoh OH, Chong YS, et al. Associations between maternal vitamin D levels during pregnancy and allergic outcomes in the offspring in the first 5 years of life. Pediatr Allergy Immunol. 2018 Oct 19. doi: 10.1111/pai.12995
25) Laird E, McNulty H, Ward M, Hoey L, McSorley E, Wallace JMW, Carson E, Molloy AM, Healy M, Casey MC, Cunningham C, Strain JJ. Vitamin D Deficiency Is Associated With Inflammation in Older Irish Adults The Journal of Clinical Endocrinology & Metabolism, 2014
26) Yip KH, Kolesnikoff N, Yu C, Hauschild N, Taing H, Biggs L, Goltzman D, Gregory PA, Anderson PH, Samuel MS, Galli SJ, Lopez AF, Grimbaldeston MA. Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation. J Allergy Clin Immunol 2014
27) Ariano R. Efficacy of a novel food supplement in the relief of the signs and symptoms of seasonal allergic rhinitis and in the reduction of the consumption of anti-allergic drugs. Acta Biomed. 2015;86(1):53-8
28) Ariano R. Ophthalmic Lertal spray for seasonal allergic conjunctivitis: an open-label clinical study. In Focus 2017;10:3-7
29) Rah MJ. A review of hyaluronan and its ophthalmic ap¬plications. Optometry. 2011;82:38-43
30) Böhm M, Avgitidou G, El Hassan E, Mosges R. Liposomes: a new non-pharmacological therapy concept for season¬al-allergic-rhinoconjunctivitis. Eur Arch Otorhinolaryngol. 2012;269:495-502
31) 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 2019;33:617-622
32) Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140(4):950-958
33) Ciprandi G, Cirillo I, Vizzaccaro A, Tosca MA, Pallestrini E. Seasonal and perennial allergic rhinitis: is this classification adherent to real life? A population based study. Allergy 2005;60:882-7
34) Marseglia GL, Licari A, Leonardi S, Papale M, Zicari AM, Schiavi L, 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
35) Portnoy JM, Dinakar C. Review of cetirizine hydrochloride for the treatment of allergic disorders. Expert Opin Pharmacother. 2004 Jan;5(1):125-35
36) Ciprandi G, Ricca V, Ferrero P, Alessandra B, Riccio AM, Milanese M, et al. Duration of antiinflammatory and symptomatic effects after suspension of intranasal corticosteroid in persistent allergic rhinitis. Eur Ann Allergy Clin Immunol. 2004;36:63-6
37) Tonelli M, Bacci E, Dente FL, Bartoli ML, Cianchetti S, Di Franco A, et al. Predictors of symptom recurrence after low-dose inhaled corticosteroid cessation in mild persistent asthma. Resp Med 2006;100:622-9
38) Wirchow JC, Backer V, Kuna P, Prieto L, Nolte H, Villesen HH, et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma. A randomized clinical trial. JAMA 2016;315:1715-25
39) Valovirta E, Petersen TH, Piotrowska T, Laursen MK, Andersen JS, Sorensen HF, et al. Results from the 5-year SQ grass sublingual immnutherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol 2018;141:529-38
40) Ciprandi G, Cosentino C, Milanese M, Mondino C, Canonica GW. Fexofenadine reduces nasal congestion in perennial allergic rhinitis Allergy 2001;56:1068-1070
41) Ciprandi G, Pronzato C, Ricca V, Varese P, Giacco GS, Canonica G. Terfenadine exerts antiallergic activity reducing ICAM‐1 expression on nasal epithelial cells in patients with pollen allergy. Clinical Experimental Allergy 1995;25:871-878
42) Ciprandi G, Buscaglia S, Catrullo A, Pesce GP, Fiorino N, Montagna P, et al. Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti‐allergic activity. Clinical Experimental Allergy 1997;27:182-91
43) Ciprandi G, Tosca MA, Passalacqua G, Canonica GW. Long-term cetirizine treatment reduces allergic symptoms and drug prescriptions in children with mite allergy. Annals of Allergy Asthma Immunol 2001;87:222-6
44) Ciprandi G, Mora F, Cassano M, Gallina AM, Mora R. Visual analog scale (VAS) and nasal obstruction in persistent allergic rhinitis. Otolaryngol Head Neck Surg 2009;141:527-9
45) Ciprandi G, Cirillo I. The lower airway pathology of Rhinitis. Update Review J Allergy Clin Immunol 2006; 118:1105-9
46) Ciprandi G, Tosca MA, Ricca V, Passalacqua G, Fregonese L, Fasce L, et al. Cetirizine treatment of allergic cough in children with pollen allergy. Allergy 1997;52:752-4
47) Ciprandi G, Marseglia GL, Klersy C, Tosca MA. Relationships between allergic inflammation and nasal airflow in children with persistent allergic rhinitis due to mite sensitization. Allergy 2005;60:957-60
48) Ciprandi G, Ricca V, Tosca MA, Landi M, Passalacqua G, Canonica G. Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy. Allergy 1999;54:358-65
2) Shin TY, Kim SH, Kim SH, et al. Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Perilla frutescens. Immunopharmacol Immunotoxicol. 2000;22(3):489-500.
3) Imaoka K, Inouye S, Takahashi et al. Effects of Perilla frutescens extract on anti-DNP IgE antibody production in mice. Arerugi. 1993;42(1):74-80.
4) Ueda H, Yamazaki C, Yamazaki M. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. . Biol Pharm Bull. 2002;25(9):1197-202
5) Makino T, Furuta Y, Wakushima H et al. Anti-allergic effect of Perilla frutescens and its active constituents. Phytother Res. 2003;17(3):240-3
6) 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 ResCommun 2017;483:674-9
7) 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
8) Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N and Nagai H. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clinical and Experimental Allergy. 2000;30:501-508
9) Theoharides TC, Kempuraj D and 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
10) Das M, Ram A and Ghosh B. Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflammation Research. 2003;52:101-106
11) Yano S, Umeda D, Yamashita T, Ninomiya T, Sumida M, Fujimura Y, Yamada K and Tachibana H. Dietary flavones suppresses IgE and Th2 cytokines in OVA-immunized BALB/c mice. European Journal of Nutrition. 2007;46:257-263
12) 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(3-4):47-52
13) Chirumbolo S. The role of Quercetin, Flavonols and Flavones in modulating inflammatory cell function. Inflamm Allergy-Drug Targets 2010; 9(4):263-85
14) Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and its anti-allergic immune response. Molecules 2016;21,623
15) Kawai M, Hirano T, Arimitsu J, et al. Effect of enzimatically modified isoquercetitrin, a flavonoid, on symptoms of Japanes cedar pollinosis: a rando,ized double-blind placebo-controlled trial. Int Arch Allergy Immunol 2009;149:359-68
16) Hirano T, Kawai M, Arimitsu J, et al. Preventative effect of a flavomnoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis Allergol Intern 2009;58:373-82
17) Ebibara N, Takahashi K, Takemura H, et al. Suppressive effect of quercetin on nitric oxide production from nasal epithelial cells in vitro. Evidence-based Complement Altern Medicine 2018;ID 6097625
18) Sakai-Kashiwabara M, Asano K. Inhibitory action of quercetin on eosinophil activation in vitro. Evidence-based Complement Altern Medicine 2013;ID 127105
19) Muehleisen B, Gallo RL J. Vitamin D in allergic disease: shedding light on a complex problem Allergy Clin Immunol. 2013;131(2):324-9
20) Bozzetto S, Carraro S, Giordano G et al. Asthma, allergy and respiratory infections: the vitamin D hypothesis. Allergy. 2012 ;67(1):10-7
21) Yepes-Nunes JJ, Brozek JL, Fiocchi A, Pawankar R, Cuello-Garcia C, Zhang Y, et al. Vitamin D supplementation in primary allergy prevention: systematic review of randomized and non-randomized studies. Allergy 2018;73:37-49
22) Kim YH, Kim KW, Kim MJ, Sol IS, Yoon SH, Ahn HS, et al. Vitamin D levels in allergic rhinitis: a systematic review and meta-analysis. Ped Allergy Immunol 2016;27:580-90
23) Aryan Z, Rezaei N, Camargo CA. Vitamin status, aeroallergen sensitization, and allergic rhinitis: a systematic review and meta-analysis. Int Rev Immunol 2017;36:41-53
24) Loo EXL, Tham EH, Phang KW, Goh A, Teoh OH, Chong YS, et al. Associations between maternal vitamin D levels during pregnancy and allergic outcomes in the offspring in the first 5 years of life. Pediatr Allergy Immunol. 2018 Oct 19. doi: 10.1111/pai.12995
25) Laird E, McNulty H, Ward M, Hoey L, McSorley E, Wallace JMW, Carson E, Molloy AM, Healy M, Casey MC, Cunningham C, Strain JJ. Vitamin D Deficiency Is Associated With Inflammation in Older Irish Adults The Journal of Clinical Endocrinology & Metabolism, 2014
26) Yip KH, Kolesnikoff N, Yu C, Hauschild N, Taing H, Biggs L, Goltzman D, Gregory PA, Anderson PH, Samuel MS, Galli SJ, Lopez AF, Grimbaldeston MA. Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation. J Allergy Clin Immunol 2014
27) Ariano R. Efficacy of a novel food supplement in the relief of the signs and symptoms of seasonal allergic rhinitis and in the reduction of the consumption of anti-allergic drugs. Acta Biomed. 2015;86(1):53-8
28) Ariano R. Ophthalmic Lertal spray for seasonal allergic conjunctivitis: an open-label clinical study. In Focus 2017;10:3-7
29) Rah MJ. A review of hyaluronan and its ophthalmic ap¬plications. Optometry. 2011;82:38-43
30) Böhm M, Avgitidou G, El Hassan E, Mosges R. Liposomes: a new non-pharmacological therapy concept for season¬al-allergic-rhinoconjunctivitis. Eur Arch Otorhinolaryngol. 2012;269:495-502
31) 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 2019;33:617-622
32) Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140(4):950-958
33) Ciprandi G, Cirillo I, Vizzaccaro A, Tosca MA, Pallestrini E. Seasonal and perennial allergic rhinitis: is this classification adherent to real life? A population based study. Allergy 2005;60:882-7
34) Marseglia GL, Licari A, Leonardi S, Papale M, Zicari AM, Schiavi L, 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
35) Portnoy JM, Dinakar C. Review of cetirizine hydrochloride for the treatment of allergic disorders. Expert Opin Pharmacother. 2004 Jan;5(1):125-35
36) Ciprandi G, Ricca V, Ferrero P, Alessandra B, Riccio AM, Milanese M, et al. Duration of antiinflammatory and symptomatic effects after suspension of intranasal corticosteroid in persistent allergic rhinitis. Eur Ann Allergy Clin Immunol. 2004;36:63-6
37) Tonelli M, Bacci E, Dente FL, Bartoli ML, Cianchetti S, Di Franco A, et al. Predictors of symptom recurrence after low-dose inhaled corticosteroid cessation in mild persistent asthma. Resp Med 2006;100:622-9
38) Wirchow JC, Backer V, Kuna P, Prieto L, Nolte H, Villesen HH, et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma. A randomized clinical trial. JAMA 2016;315:1715-25
39) Valovirta E, Petersen TH, Piotrowska T, Laursen MK, Andersen JS, Sorensen HF, et al. Results from the 5-year SQ grass sublingual immnutherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol 2018;141:529-38
40) Ciprandi G, Cosentino C, Milanese M, Mondino C, Canonica GW. Fexofenadine reduces nasal congestion in perennial allergic rhinitis Allergy 2001;56:1068-1070
41) Ciprandi G, Pronzato C, Ricca V, Varese P, Giacco GS, Canonica G. Terfenadine exerts antiallergic activity reducing ICAM‐1 expression on nasal epithelial cells in patients with pollen allergy. Clinical Experimental Allergy 1995;25:871-878
42) Ciprandi G, Buscaglia S, Catrullo A, Pesce GP, Fiorino N, Montagna P, et al. Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti‐allergic activity. Clinical Experimental Allergy 1997;27:182-91
43) Ciprandi G, Tosca MA, Passalacqua G, Canonica GW. Long-term cetirizine treatment reduces allergic symptoms and drug prescriptions in children with mite allergy. Annals of Allergy Asthma Immunol 2001;87:222-6
44) Ciprandi G, Mora F, Cassano M, Gallina AM, Mora R. Visual analog scale (VAS) and nasal obstruction in persistent allergic rhinitis. Otolaryngol Head Neck Surg 2009;141:527-9
45) Ciprandi G, Cirillo I. The lower airway pathology of Rhinitis. Update Review J Allergy Clin Immunol 2006; 118:1105-9
46) Ciprandi G, Tosca MA, Ricca V, Passalacqua G, Fregonese L, Fasce L, et al. Cetirizine treatment of allergic cough in children with pollen allergy. Allergy 1997;52:752-4
47) Ciprandi G, Marseglia GL, Klersy C, Tosca MA. Relationships between allergic inflammation and nasal airflow in children with persistent allergic rhinitis due to mite sensitization. Allergy 2005;60:957-60
48) Ciprandi G, Ricca V, Tosca MA, Landi M, Passalacqua G, Canonica G. Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy. Allergy 1999;54:358-65
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1.
Complementary treatment of allergic rhinoconjunctivitis: the role of the nutraceutical Lertal(R). Acta Biomed [Internet]. 2020 Mar. 19 [cited 2024 Jun. 30];91(1):97-106. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/9275
