Inhibitory Effect of Pycnogenol® on Airway Inflammation in Ovalbumin-Induced Allergic Rhinitis

Abstract

Background: The supplement Pycnogenol® (PYC) has been used for the treatment of several chronic diseases including allergic rhinitis (AR). However, the in vivo effects on allergic inflammation have not been identified to date. Aims: To investigate the treatment results of PYC on allergic inflammation in a rat model of allergic rhinitis.  Study Design: Animal experimentation. Methods: Allergic rhinitis was stimulated in 42 rats by intraperitoneal sensitization and intranasal challenge with Ovalbumin. The animals were divided into six subgroups: healthy controls, AR group, AR group treated with corticosteroid (dexamethasone 1 mg/kg; CS+AR), healthy rats group that were given only PYC of 10 mg/kg (PYC10), AR group treated with PYC of 3mg/kg (PYC3+AR), and AR group treated with PYC of 10 mg/kg (PYC10+AR). Interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), and OVA-specific immunoglobulin E (Ig-E) levels of serum were measured. Histopathological changes in nasal mucosa and expression of tumor necrosis factor-α (TNF-α) and IL-1β were evaluated. Results: The levels of the IL-4 were significantly decreased in the PYC3+AR, PYC10+AR  and CS+AR  groups compared with the AR group (p=0.002, p<0.001, p=0.006). The production of the IFN-γ was significantly decreased in the PYC3+AR  and PYC10+AR groups compared with the AR group (p=0.013, p=0.001). The administration of PYC to allergic rats suppressed the elevated IL-10 production, especially in the PYC3+AR group (p=0.006). Mucosal edema was significantly decreased respectively after treatment at dose 3 mg/kg and 10 mg/kg PYC (both, p<0.001). The mucosal expression of TNF-α has significantly decreased in the PYC3+AR and PYC10+AR groups (p=0.005, p<0.001), while the IL-1β expression significantly decreased in the CS+AR, PYC3+AR, and PYC10+AR groups (p<0.001, p=0.003, p=0.001). Conclusion: PYC has multiple suppressive effects on allergic response. Thus, PYC may be used as a supplementary agent in allergic response.

Keywords

• Pycnogenol, allergic rhinitis, IL-4, IL-10, OVA-specific IgE, TNF-α, IL-1β, eosinophil, edema, goblet cell

References

1. 1. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization,GA(2)LEN and AllerGen). Allergy 2008;63(Suppl 86):8-160. [CrossRef]
2. 2. El Gazzar M, El Mezayen R, Marecki JC, Nicolls MR, Canastar A, Dreskin SC. Anti-inflammatory effect of Pycnogenol in a mouse model of allergic lung inflammation. Int Immunopharmacol 2006;6:1135-42. [CrossRef]
3. 3. Kleinjan A, van Nimwegen M, Leman K, Hoogsteden HC, Lambrecht BN. Topical treatment targeting sphingosine-1-phosphate and sphingosine lyase abrogates experimental allergic rhinitis in a murine model. Allergy 2013;68:204-12. [CrossRef
4. 4. Jung HW, Jung JK, Park YK. Comparison of the efficacy of KOB03, ketotifen, and montelukast in an experimental mouse model of allergic rhinitis. Int Immunopharmacol 2013;16:254- 60. [CrossRef]
5. 5. Valovirta E, Myrseth SE, Palkonen S. The voice of the patients: allergic rhinitis is not a trivial disease. Curr Opin Allergy Clin Immunol 2008;8:1-9. [CrossRef]
6. 6. Kim BY, Shin JH, Park HR, Kim SW, Kim SW. Comparison of antiallergic effects of pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine in a murine model of allergic rhinitis. Laryngoscope 2013;123:2371-7. [CrossRef]
7. 7. Wilson D, Evans M, Guthrie N, Sharma P, Baisley J, Schonlau F, et al. A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of pycnogenol for improving allergic rhinitis symptoms. Phytother Res 2010;24:1115-9. [CrossRef]
8. 8. Taner G, Aydın S, Aytaç Z, Başaran AA, Başaran N. Assessment of the cytotoxic, genotoxic, and antigenotoxic potential of Pycnogenol® in in vitro mammalian cells. Food Chem Toxicol 2013;61:203-8. [CrossRef]

9. 9. Shin IS, Shin NR, Jeon CM, Hong JM, Kwon OK, Kim JC, et al. Inhibitory effects of Pycnogenol® (French maritime pine bark extract) on airway inflammation in ovalbumin-induced allergic asthma. Food and Chem Toxicol 2013;62:681-6. [CrossRef]
10. 10. Choi YH, Yan GH. Pycnogenol inhibits immunoglobulin E-mediated allergic response in mast cells. Phytother Res 2009;23:1691-5. [CrossRef]
11. 11. Lau BH, Riesen SK, Truong KP, Lau EW, Rohdewald P, Barreta RA. Pycnogenol as an adjunct in the management of childhood asthma. J Asthma 2004;41:825-2. [CrossRef]
12. 12. Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R,Watson RR. Pycnogenol® in the management of asthma. J Med Food 2001;4:201-9. [CrossRef]
13. 13. Wang W, Zheng M. Nuclear factor kappa B pathway downregulates aquaporin 5 in the nasal mucosa of rats with allergic rhinitis. Eur Arch Otorhinolaryngol 2011;268:73-81. [CrossRef]
14. 14. Xu YY, Liu X, Dai LB, Zhou SH. Effect of Tong Qiao drops on the expression of eotaxin, IL-13 in the nasal mucosa of rats with allergic rhinitis. J Chin Med Assoc 2012;75:524-9. [CrossRef]
15. 15. Schoonees A, Visser J, Musekiwa A, Volmink J. Pycnogenol® (extract of French maritime pine bark) for the treatment of chronic disorders. Cochrane Database Syst Rev 2012;18:CD008294. [CrossRef]
16. 16. Mei L, Mochizuki M, Hasegawa N. Hepatoprotective effects of pycnogenol in a rat model of non-alcoholic steatohepatitis. Phytother Res 2012;26:1572-4. [CrossRef]
17. 17. Tatar A, Parlak SN, Yayla M, Ugan RA, Polat E, Halici Z. Effects of allergic rhinitis and desloratadine on the submandibular gland in a rat allergy model. Int Forum Allergy Rhinol 2015;5:1164-9. [CrossRef]
18. 18. Wang W, Zheng M. Nuclear factor kappa B pathway downregulates aquaporin 5 in the nasal mucosa of rats with allergic rhinitis. Eur Arch Otorhinolaryngol 2011;268:73-81. [CrossRef]
19. 19. Settipane RA, Schwindt C. Chapter 15: Allergic rhinitis. Am J Rhinol Allergy 2013;27(Suppl 1):52-5. [CrossRef]
20. 20. Ying S, Durham SR, Corrigan CJ, Hamid Q, Kay AB. Phenotype of cells expressing mRNA for Th2-type (interleukin 4 and interleukin 5) and Th1-type (interleukin 2 and interferon gamma) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatic and normal control subjects. Am J Respir Cell Mol Biol 1995;12:477-87. [CrossRef]
21. 21. Benson M, Strannegård IL, Strannegård O, Wennergren G. Topical steroid treatment of allergic rhinitis decreases nasal fluid TH2 cytokines, eosinophils, eosinophil cationic protein, and IgE but has no significant effect on IFN-gamma, IL-1beta, TNFalpha, or neutrophils. J Allergy Clin Immunol 2000;106:307-12. [CrossRef]
22. 22. Wang H, Barrenäs F, Bruhn S, Mobini R, Benson M. Increased IFN-gamma activity in seasonal allergic rhinitis is decreased by corticosteroid treatment. J Allergy Clin Immunol 2009;124:1360- 2. [CrossRef]
23. 23. Osguthorpe JD. Pathophysiology of and potential new therapies for allergic rhinitis. Int Forum Allergy Rhinol 2013;3:384-92. [CrossRef]
24. 24. König K, Klemens C, Eder K, San Nicoló M, Becker S, Kramer MF, et al. Cytokine profiles in nasal fluid of patients with seasonal or persistent allergic rhinitis. Allergy Asthma Clin Immunol 2015;11:26. [CrossRef]
25. 25. Zhang HQ, Sun Y, Xu F. Therapeutic effects of interleukin-1 receptor antagonist on allergic rhinitis of guinea pig. Acta Pharmacol Sin 2003;24:251-5.