Effects of Viola tricolor Flower Hydroethanolic Extract on Lung Inflammation in a Mouse Model of Chronic Asthma
Asthma is a chronic inflammatory disease of the lungs driven by T cell activation. Viola tricolor L. as a traditional medical herb could suppress activated T lymphocytes and has been used empirically for asthma remedy. In the present study, we investigated the anti-inflammatory effect of Viola tricolor and its underlying mechanism on asthma characteristics induced by ovalbumin (OVA) in mice. BALB/c mice were randomly divided into six groups: normal control, Ovalbumin (OVA) control, OVA mice treated with Viola tricolor (50, 100 and 200 mg/kg) and dexamethasone (3 mg/kg). All mice except normal controls were sensitized and challenged with OVA. Asthmatic mice were treated orally in the last 7 days of OVA challenge. The total and differential leukocyte counts, Interleukin (IL)-4 and interferon (IFN)-γ levels in bronchoalveolar lavage fluid (BALF) were determined. H and E staining for lung inflammation was performed. Viola tricolor treatment at 200 mg/kg significantly decreased IL-4 level but did not considerably affect the IFN-γ level. Therefore, it effectively reduced asthma characteristics including infiltration of leukocytes particularly eosinophil and peribronchial inflammation as compared to dexamethasone. However, Viola tricolor at 100 mg/kg had the most prominent inhibitory effect on the IL-4 level and also markedly increased IFN-γ level. As result, it prevented further reduction of inflammatory parameters in this group compared to the Viola tricolor-treated group at 200 mg/kg. Our study demonstrated that Viola tricolor has anti-inflammatory effects via inhibition of T-helper type 2 (Th2) cytokine production and validated its empirical usage in traditional medicine.
1. George L, Brightling CE. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther Adv Chronic Dis 2016;7(1):34-51.
2. Kim Y-M, Kim Y-S, Jeon SG, Kim Y-K. Immunopathogenesis of Allergic Asthma: More Than the Th2 Hypothesis. Allergy Asthma Immunol Res 2013;5(4):189-96.
3. Gour N, Wills-Karp M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine 2015;75(1):68-78.
4. Chung KF. Targeting the interleukin pathway in the treatment of asthma. Lancet 2015;386(9998):1086-96.
5. Foster PS, Maltby S, Rosenberg HF, Tay HL, Hogan SP, Collison AM, et al. Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunol Rev 2017;278(1):20-40.
6. Metcalfe DD, Pawankar R, Ackerman SJ, Akin C, Clayton F, Falcone FH, et al. Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases. World Allergy Organ J 2016;9(1):7.
7. Ishmael FT. The inflammatory response in the pathogenesis of asthma. TJ Am Osteopath Assoc 2011;111(11 Suppl 7):S11-7.
8. Possa SS, Leick EA, Prado CM, Martins MA, Tibério IF. Eosinophilic inflammation in allergic asthma. Front Pharmacol 2013;4.
9. Teixeira LK, Fonseca BP, Barboza BA, Viola JP. The role of interferon-gamma on immune and allergic responses. Mem Inst Oswaldo Cruz 2005;100:137-44.
10. Raundhal M, Morse C, Khare A, Oriss TB, Milosevic J, Trudeau J, et al. High IFN-γ and low SLPI mark severe asthma in mice and humans. J Clin Invest 2015;125:3037-50.
11. Yu M, Eckart MR, Morgan AA, Mukai K, Butte AJ, Tsai M, et al. Identification of an IFN-γ/mast cell axis in a mouse model of chronic asthma. J Clin Invest 2011;121:3133-43.
12. Ford JG, Rennick D, Donaldson DD, Venkayya R, McArthur C, Hansell E, et al. IL-13 and IFN-γ: interactions in lung inflammation. J Immunol 2001;167:1769-77.
13. Liu F, Xuan N-X, Ying S-M, Li W, Chen Z-H, Shen H-H. Herbal medicines for asthmatic inflammation: from basic researches to clinical applications. Mediators Inflamm 2016;2016.
14. Li X-M, Brown L. Efficacy and mechanisms of action of traditional Chinese medicines for treating asthma and allergy. J Allergy Clin Immunol 2009;123:297-306.
15. Hellinger R, Koehbach J, Fedchuk H, Sauer B, Huber R, Gruber CW, et al. Immunosuppressive activity of an aqueous Viola tricolor herbal extract. J Ethnopharmacol 2014;151:299-306.
16. European Medicines Agency, Committee on Herbal Medicinal Products (HMPC), Community herbal monograph on Viola tricolor L., and/or subspecies Viola arvensis Murray (Gaud) and Viola vulgaris Koch (oborny), Herba cum Flore 2010; EMA/HMPC/131734/2009.
17. Mohammadian M, Boskabady MH, Kashani IR, Jahromi GP, Omidi A, Nejad AK, et al. Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse. Iran J Basic Med Sci 2016;19:55.
18. Raemdonck K, Birrell MA, Gozzard N, Chung KF, Belvisi MG, Adcock IM. Corticosteroid insensitivity in a house dust mite and freund's complete adjuvant driven mouse model of allergic asthma. Am J Respir Crit Care Med 2014;189:A4193.
19. Mohammadian M, Sadeghipour HR, Kashani IR, Jahromi GP, Omidi A, Nejad AK, et al. Evaluation of simvastatin and bone marrow-derived mesenchymal stem cell combination therapy on airway remodeling in a mouse asthma model. Lung 2016;194:777-85.
20. Beasley R, Semprini A, Mitchell EA. Risk factors for asthma: is prevention possible? Lancet 2015;386:1075-85.
21. Nials AT, Uddin S. Mouse models of allergic asthma: acute and chronic allergen challenge. Dis Model Mech 2008;1:213-20.
22. Finkelman FD, Hogan SP, Hershey GK, Rothenberg ME, Wills-Karp M. Importance of cytokines in murine allergic airway disease and human asthma. J Immunol 2010;184(4):1663-74.
23. Sellers R, Clifford C, Treuting P, Brayton C. Immunological variation between inbred laboratory mouse strains: points to consider in phenotyping genetically immunomodified mice. Vet Pathol 2012;49:32-43..
24. Xu S, Tian B-P, Zhang L-H, Hua W, Xia L-X, Chen Z-H, et al. Prevention of allergic airway hyperresponsiveness and remodeling in mice by Astragaliradix Antiasthmatic decoction. BMC Complement Altern Med 2013;13:369.
25. Jovicic N, Jeftic I, Jovanovic I, Radosavljevic G, Arsenijevic N, Lukic ML, et al. Differential immunometabolic phenotype in Th1 and Th2 dominant mouse strains in response to high-fat feeding. PloS one 2015;10(7):e0134089.
26. Kubo M. Innate and adaptive type 2 immunity in lung allergic inflammation. Immunol Rev 2017;278(1):162-72.
27. Piana M, Silva MA, Trevisan G, de Brum TF, Silva CR, Boligon AA, et al. Antiinflammatory effects of Viola tricolor gel in a model of sunburn in rats and the gel stability study. J Ethnopharmacol 2013;150(2):458-65.
28. Nakagome K, Okunishi K, Imamura M, Harada H, Matsumoto T, Tanaka R, et al. IFN-γ attenuates antigen-induced overall immune response in the airway as a Th1-type immune regulatory cytokine. J Immunol 2009;183(1):209-20.
29. Mitchell C, Provost K, Niu N, Homer R, Cohn L. IFN-γ acts on the airway epithelium to inhibit local and systemic pathology in allergic airway disease. J Immunol 2011;187(7):3815-20.