In Vitro Antiallergic Effects of Aqueous Fermented Preparations from Citrus and Cydonia fruits

Abstract

This study aimed to investigate the immunomodulatory and antiallergic properties of preparations from lemon, Citrus medica L. (Citrus), and quince, Cydonia oblonga Mill. (Cydonia), which are used in pharmaceutical products to treat patients suffering from allergic disorders. Preparations were analyzed with respect to their impact on the degranulation capacity from basophilic cells as well as mediator release from activated human mast cells in vitro, including IL-8 and TNF-α secretion. The results show that the degranulation of basophilic cells was diminished only in the presence of Citrus, and this effect was compared to the synthetic drug azelastine. Furthermore, Citrus and Cydonia both inhibited the production of IL-8 and TNF-α from human mast cells, and at low concentrations additive effects were observed. As a positive inhibition control, dexamethasone was used. LC-MS analyses showed that the major phenolic components in extracts from Citrus and Cydonia are eriocitrin and neochlorogenic acid, respectively. Nevertheless, these compounds do not show biological effects at concentration levels detected in their corresponding extracts. In conclusion, the present data provide a rational base for the use of the single pharmaceutical preparations from Citrus and Cydonia in a differentiated treatment of allergic disorders in part by the regulation of soluble allergic mediators from basophilic cells and mast cells.

Citrus medica - Rutaceae - Cydonia oblonga - Rosaceae - allergy - phenolics - anthroposophical medicine

References

• 1 Pearlman D S. Pathophysiology of the inflammatory response.  J Allergy Clin Immunol. 1999;  104 132-137
• 2 Gould H J, Sutton B J. IgE in allergy and asthma today.  Nat Rev Immunol. 2008;  8 205-217
• 3 Greiner A N, Meltzer E O. Pharmacologic rationale for treating allergic and nonallergic rhinitis.  J Allergy Clin Immunol. 2006;  118 985-996
• 4 Juniper E F, Stahl E, Doty R L, Simons F E, Allen D B, Howarth P H. Clinical outcomes and adverse effect monitoring in allergic rhinitis.  J Allergy Clin Immunol. 2005;  115 390-413
• 5 Mainardi T, Kapoor S, Bielory L. Complementary and alternative medicine: herbs, phytochemicals and vitamins and their immunologic effects.  J Allergy Clin Immunol. 2009;  123 283-294
• 6 Rother C, Oexle J. Untersuchung zur Ermittlung des Anwendungsnutzens von Weleda Heuschnupfenspray unter besonderer Berücksichtigung der Wirkungsdynamik. Ergebnisse einer prospektiven Beobachtungsstudie.  Der Merkurstab/J Anthroposophic Med. 2008;  61 167-171
• 7 Baars E W, Savelkoul H F J. Citrus/Cydonia comp. can restore the immunological balance in seasonal allergic rhinitis-related immunological parameters in vitro.  Mediators Inflamm. 2008;  DOI: 10.1155/2008/496467
• 8 Gründemann C, Papagiannopolous M, Lamy M, Mersch-Sundermann M, Huber R. Immunomodulatory properties of a lemon-quince preparation (Gencydo®) as an indicator of antiallergic potency.  Phytomedicine. 2011;  18 760-768
• 9 German Homeopathic Pharmacopoeia (GHP). including 7th Supplement, Volume 1 and 2. Stuttgart: Federal Institute for Drugs and Medical Devices BfArM; 2010
• 10 Rivera J, Gilfillan A M. Molecular regulation of mast cell activation.  J Allergy Clin Immunol. 2006;  117 1214-1225
• 11 Galli S J, Kalesnikoff J, Grimbaldeston M A, Piliponsky A M, Williams C M M, Tsai M. Mast cells as “tunable” effector and immunoregulatory cells: recent advances.  Annu Rev Immunol. 2005;  23 749-786
• 12 Park H H, Lee S, Son H Y, Park S B, Kim M S, Choi E J, Singh T S K, Ha J H, Lee M G, Kim J E, Hynn M C, Kwon T K, Kim K H, Kim S H. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells.  Arch Pharm Res. 2008;  31 1303-1311
• 13 Shinomiya F, Hamauzu Y, Kawahara T. Anti-allergic effect of a hot-water extract of quince (Cydonia oblonga).  Biosci Biotechnol Biochem. 2009;  73 1773-1778
• 14 Kawahara T, Iizuka T. Inhibitory effect of hot-water extract of quince (Cydonia oblonga) on immunoglobulin-dependent late-phase immune reactions of mast cells.  Cytotechnology. 2011;  63 143-152
• 15 Hide I, Toriu N, Nuibe T, Inoue A, Hide M, Yamamoto S, Nakata Y. Suppression of TNF-alpha secretion by azelastine in a rat mast (RBL-2H3) cell line – evidence for differential regulation of TNF-alpha release, transcription, and degranulation.  J Immunol. 1997;  159 2932-2940
• 16 Silva B M, Andrade P B, Ferreres F, Domingues A L, Seabra R M, Ferreira M A. Phenolic profile of quince fruit (Cydonia oblonga Miller) (pulp and peel).  J Agric Food Chem. 2002;  50 4615-4618
• 17 Silva B M, Andrade P B, Gonçalves A C, Seabra R M, Oliveira M B, Ferreira M A. Influence of jam processing upon the contents of phenolics, organic acids and free amino acids in quince fruit (Cydonia oblonga Miller).  Eur Food Res Technol. 2004;  218 385-389
• 18 Silva B M, Andrade P B, Martins R C, Valentão P, Ferreres F, Seabra R M, Ferreira M A. Quince (Cydonia oblonga Miller) fruit characterization using principal component analysis.  J Agric Food Chem. 2005;  53 111-122
• 19 Hamauzu Y, Yasui H, Inno T, Kume C, Omanyuda M. Phenolic profile, antioxidant property, and anti-influenza viral activity of Chinese quince (Pseudocydonia sinensis Schneid.), quince (Cydonia oblonga Mill.), and apple (Malus domestica Mill.) fruits.  J Agric Food Chem. 2005;  53 928-934
• 20 Alesiani D, Canini A, d'Abrosca B, DellaGreca M, Fiorentino A, Mastellone C, Monaco P, Pacifico S. Antioxidant and antiproliferative activities of phytochemicals from quince (Cydonia vulgaris) peels.  Food Chem. 2010;  118 199-207
• 21 Fiorentino A, D'Abrosca B, Pacifico S, Mastelone C, Piscopo V, Caputo R, Monaco P. Isolation and structure elucidation of antioxidant polyphenols from quince (Cydonia vulgaris) peels.  J Agric Food Chem. 2008;  56 2660-2667
• 22 Caristi C, Bellocco E, Garguilli C, Toscano G, Leuzi U. Flavone-di-C-glycosides in citrus juices from Southern Italy.  Food Chem. 2005;  95 431-437
• 23 Manthey J A, Grohmann K. Phenols in Citrus peel byproducts. Concentration of hydroxycinnamates and polymethoxylated flavones in citrus peel molasses.  J Agric Food Chem. 2001;  49 3268-3273
• 24 Sun Y, Wang J, Gu S, Liu Z, Zhang Y, Zhang X. Simultaneous determination of flavonoids in different parts of Citrus reticulata ‘Chachi fruit by high performance liquid chromatography-photodiode array detection.  Molecules. 2010;  15 5378-5388
• 25 Ho S C, Lin C C. Investigation of heat treating conditions for enhancing the anti-inflammatory activity of Citrus fruit (Citrus reticulata) peels.  J Agric Food Chem. 2008;  56 7976-7982
• 26 Belajová E, Suhaj M. Determination of phenolic constituents in citrus juices: Method for high performance liquid chromatography.  Food Chem. 2004;  86 339-343
• 27 Jang H D, Chang K S, Chang T C, Hsu C L. Antioxidant potentials of buntan pumelo (Citrus grandis Osbeck) and its ethanolic and acetified fermentation products.  Food Chem. 2010;  118 554-558
• 28 Xu G, Liu D, Chen J, Ye X, Shi J. Composition of major flavanone glycosides and antioxidant capacity of three Citrus varieties.  J Food Biochem. 2009;  33 453-469
• 29 Ramful D, Bahorun T, Bourdon E, Tarnus E, Aruoma O I. Bioactive phenolics and antioxidant prospensity of flavedo extracts of Mauritian citrus fruits: potential prophylactic ingredients for functional food applications.  Toxicology. 2010;  278 75-87
• 30 Lorenz P, Conrad J, Bertrams J, Berger M, Duckstein S, Meyer U, Stintzing F C. Investigations into the phenolic constituents of dog's mercury (Mercurialis perennis L.) by LC-MS/MS and GC-MS analyses.  Phytochem Anal. 2012;  23 60-71
• 31 McKay D L, Blumberg J B. A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.).  Phytother Res. 2006;  20 619-633
• 32 Takahashi A, Nakata K. Anti-inflammatory effects of peppermint.  Aromatopia. 1995;  13 42-45
• 33 Huang F H, Zhang X Y, Zhang L Y, Li Q, Ni B, Zheng X L, Chen A J. Mast cell degranulation induced by chlorogenic acid.  Acta Pharmacol Sin. 2010;  31 849-854
• 34 Kimura Y, Okuda H, Okuda T, Hatano T, Agata I, Arichi S. Studies on the activities of tannins and related compounds from medicinal plants and drugs. VI. Inhibitory effects of caffeoylquinic acids on histamine release from rat peritoneal mast cells.  Chem Pharm Bull. 1985;  33 690-696
• 35 Qin H D, Shi Y Q, Liu Z H, Li Z G, Wang H S, Wang H, Liu Z P. Effect of chlorogenic acid on mast cell-dependent anaphylactic reaction.  Int Immunopharmacol. 2010;  10 1135-1141
• 36 Kim H R, Lee D M, Lee S H, Seong A R, Gin D W, Hwang J A, Park J H. Chlorogenic acid suppresses pulmonary eosinophilia, IgE production, and Th2-type cytokine production in an ovalbumin-induced allergic asthma: activation of STAT-6 and JNK are inhibited by chlorogenic acid.  Int Immunopharmacol. 2010;  10 1242-1248
• 37 Chen S S, Gong J, Liu F T, Mohammed U. Naturally occuring polyphenolic antioxidants modulate IgE-mediated mast cell activation.  Immunology. 2000;  100 471-480