Original Article
 

Immunomodulatory Effect of SINA 1.2 Therapy Protocol in Asthmatic Mice Model: A Combination of Oxymel and Sauna

Abstract

Alternative medicine, has become popular in asthmatic patients. We evaluated the immunomodulatory effects of SINA 1.2 therapy protocol derived from Persian medicine in an asthmatic mice model.
Forty-two male BALB/c mice divided into six groups: one control (sham) and five sensitized groups (by parenteral injection of 20 μg ovalbumin in 100 μL normal saline plus 50 μL alum on days 1 and 14). Sensitized groups were as: untreated, budesonide (1 mg nebulized budesonide: 200 μg/puff every 5 min for 25 min), dry sauna (30 min, 37°C), oral oxymel (gavaged: 0.2 mL of the syrup plus 0.8 mL of water), and SINA protocol No.1.2 (oxymel followed by sauna) groups. Treatments were given for 10 days from day 23 to 33 then sacrificed.
Significant gene expression reduction of interleukin(IL)-4, IL-5, and MUC5AC and increase of interferon(IFN)-γ and IFN-γ/IL-4 ratio and decreased perivascular and peribronchial inflammation, goblet cell hyperplasia, and subsequent mucus hypersecretion in SINA group were seen compared to untreated group. SINA lowered IL-5 and MUC5AC gene expression levels similar to the budesonide and acted better than budesonide in increasing IFN-γ gene expression up to normal level. Compared with the asthma group, sauna alone only affected MUC5AC and IFN-γ gene expressions and oxymel alone, only reduced IL-4 gene expression, perivascular and peribronchial inflammation, and mucus hypersecretion.
It seems that SINA therapy alleviates asthma via immune modulation of pro-inflammatory cytokines and improvement of pathological changes in ovalbumin-induced asthma in mice, supporting the notion of innate healing power mentioned in Persian medicine literature.

1. Pawankar R. Allergic diseases and asthma: a global public health concern and a call to action. World Allergy Organ J. 2014;7(1):12.
2. Bousquet J, Bousquet PJ, Godard P, Daures JP. The public health implications of asthma. Bull World Health Organ. 2005;83(7):548-54.
3. Organization WH. Asthma Fact Sheet. 2021. [cited 3 May 2021] available from: https://wwwwhoint/news-room/fact-sheets/detail/asthma. 2021.
4. Mehra PK, Woessner KM. Dyspnea, wheezing, and airways obstruction: is it asthma? Allergy Asthma Proc. 2005;26(4):319-22.
5. Matucci A, Vultaggio A, Maggi E, Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res. 2018;19(1):113.
6. Oettgen HC, Geha RS. IgE regulation and roles in asthma pathogenesis. J Allergy Clin Immunol. 2001;107(3):429-40.
7. Athari SS, Athari SM, Beyzay F, Movassaghi M, Mortaz E, Taghavi M. Critical role of Toll-like receptors in pathophysiology of allergic asthma. Eur J Pharmacol. 2017;808(21):21-7.
8. Renauld JC. New insights into the role of cytokines in asthma. J Clin Pathol. 2001;54(8):577-89.
9. Kanoh S, Tanabe T, Rubin BK. IL-13-induced MUC5AC production and goblet cell differentiation is steroid resistant in human airway cells. Clin Exp Allergy. 2011;41(12):1747-56.
10. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282(5397):2258-61.
11. Blaeser F, Bryce PJ, Ho N, Raman V, Dedeoglu F, Donaldson DD, et al. Targeted inactivation of the IL-4 receptor alpha chain I4R motif promotes allergic airway inflammation. J Exp Med. 2003;198(8):1189-200.
12. Renz H, Enssle K, Lauffer L, Kurrle R, Gelfand EW. Inhibition of allergen-induced IgE and IgG1 production by soluble IL-4 receptor. Int Arch Allergy Immunol. 1995;106(1):46-54.
13. Tanaka H, Kawada N, Yamada T, Kawada K, Takatsu K, Nagai H. Allergen-induced airway inflammation and bronchial responsiveness in interleukin-5 receptor alpha chain-deficient mice. Clin Exp Allergy. 2000;30(6):874-81.
14. Bonser LR, Erle DJ. Airway Mucus and Asthma: The Role of MUC5AC and MUC5B. J Clin Med. 2017;6(12):26-9.
15. 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.
16. Han M, Hong JY, Jaipalli S, Rajput C, Lei J, Hinde JL, et al. IFN-γ Blocks Development of an Asthma Phenotype in Rhinovirus-Infected Baby Mice by Inhibiting Type 2 Innate Lymphoid Cells. Am J Respir Cell Mol Biol. 2017;56(2):242-51.
17. Bosnjak B, Stelzmueller B, Erb KJ, Epstein MM. Treatment of allergic asthma: modulation of Th2 cells and their responses. Respir Res. 2011;12(1):114.
18. D'Amato G, Vitale C, Molino A, Stanziola A, Sanduzzi A, Vatrella A, et al. Asthma-related deaths. Multidiscip Respir Med. 2016;11:37.
19. Sumino K, Cabana MD. Medication adherence in asthma patients. Curr Opin Pulm Med. 2013;19(1):49-53.
20. Qi Z. Who traditional medicine strategy 2014-2023. Geneva: World Health Organization. 2013.
21. George M, Topaz M, RN. The effectiveness of alternative medicine in the treatment of asthma. Nurs Clin North Am. 2013 48(1): 0.1016/j.cnur.2012.11.002
22. Abolhassani H, Naseri M, Mahmoudzadeh S. A survey of complementary and alternative medicine in Iran. Chin J Integr Med. 2012;18(6):409-16.
23. Amini F, Jaladat AM, Atarzadeh F, Mosavat SH, Parvizi MM, Zamani N. A review on the management of asthma in the Avicenna's Canon of Medicine. J Complement Integr Med 2019;16(4), doi: 10.1515/jcim-2018-0148..
24. Karegar-Borzi H. The effect of squill oxymel, a Traditional Iranian Medicine product, on treatment of asthmatic patients: a triple-blind randomized Clinical trial [Persian Medicine PhD thesis]. Tehran, Iran: Tehran University of Medical Sciences 2017.
25. Faryabi R. The effect of SINA1.2 protocol, a combination of a specific dry sauna and oral oxymel on air way histopathologic changes due to Ovalbomin-induced asthma in the Balb/c mice [Persian Medicine PhD thesis]: Tehran University of Medical Sciences; 2020.
26. Mahdi Alizadeh V, Ayeh N, Nahid B. The Concept of the Haar-re-Gharizi and Hararate Gharizi: The Innate Hot [Substance] and Heat. Trad Integr Med. 2017;2(1):1-4.
27. Sarbaz Hoseini Z, Alizadeh Vaghasloo M, Ababzadeh S, Heidari H, Mohammadbeigi A, Khalaj A, et al. The Effect of Combination Therapy (Thermal Therapy and Oxymel) on Insulin Resistance and Langerhans Islands in Diabetic Rats. Iran Red Crescent Med J. 2019;21(8):3-6.
28. Zahra Sarbaz H, Majid A, Hamid H, Abolfazl M, Mahdi Alizadeh V. Novel Thermal-Therapy Protocol (SINA1.2) from Traditional Persian Medicine (TPM): A Pilot on Diabetic Rats. Trad Integr Med. 2019;4(3):6-9.
29. Narges Sharifi D, Glen Michael C, Mahdi Alizadeh V. Introduction to the Concept of Crisis in Diseases. Trad Integr Med. 2019;4(4):8-10.
30. Babashahi N. Designing laboratory model of Dry sauna based on principles of Iranian Traditional Medicine (SINA therapy) and determine its effect on fatty liver in rat, [Masters in Medical Physiology Thesis]. Tehran, Iran: Shahed University; 2017.
31. Vahid A. The explanation of the theoretical aspects of the concept of "strength and weakness of the heart" in Iranian Traditional Medicine (Persian medicine) and Determining the relationship between heart reinforcement by SINA-therapy 1-3 protocol with fear level in rat [Persian Medicine PhD thesis]. Tehran, Iran: Shahid Beheshti University of Medical Science;2020.
32. Vakilinia SR, Vaghasloo MA, Aliasl F, Mohammadbeigi A, Bitarafan B, Etripoor G, et al. Evaluation of the efficacy of warm salt water foot-bath on patients with painful diabetic peripheral neuropathy: A randomized clinical trial. Complement Ther Med. 2020;49:102325.
33. Mahdi A-V, Mohammad-Ali Z, Sayed-Mohammad A-S. The Concept of Nozj. Trad Integr Med. 2016;1(4):6-9.
34. Fatemeh M, Fatemeh A, Ayeh N, Mehrdad K, Mahdi Alizadeh V. The Concept of “Masam” (Pores) in Persian Medicine. Trad Integr Med. 2017;2(4):9-11.
35. Mahdi Alizadeh V, Ayeh N, Mansoor K. The Concept of Pulse. Trad Integr Med. 2017;2(2).
36. Wang X, Ouyang Y, Liu J, Zhu M, Zhao G, Bao W, et al. Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies. Bmj. 2014;349:g4490.
37. Derakhshandeh-Rishehri SM, Heidari-Beni M, Feizi A, Askari GR, Entezari MH. Effect of honey vinegar syrup on blood sugar and lipid profile in healthy subjects. Int J Prev Med. 2014;5(12):1608-15.
38. Kianmeher M, Ghorani V, Boskabady MH. Animal Model of Asthma, Various Methods and Measured Parameters: A Methodological Review. Iran J Allergy Asthma Immunol. 2016;15(6):445-65.
39. Yu ZW, Zhang JH. Effect of inhaled budesonide on surfactant protein expression in asthmatic mice. Allergy Asthma Proc. 2008;29(5):486-92.
40. Aghili Shirazi M. Gharabadin Kabir. 2. Tehran: Almai; 2018. p. 1145 [in Persian].
41. Schuetze S, Manig A, Ribes S, Nau R. Aged mice show an increased mortality after anesthesia with a standard dose of ketamine/xylazine. Lab Anim Res. 2019;35:8.
42. Heydari M, Mokhtari-Zaer A, Amin F, Memarzia A, Saadat S, Hosseini M, et al. The effect of Zataria multiflora hydroalcoholic extract on memory and lung changes induced by rats that inhaled paraquat. Nutr Neurosci. 2019;24(9):674-8.
43. Athari SS, Pourpak Z, Folkerts G, Garssen J, Moin M, Adcock IM, et al. Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice. Eur J Pharmacol. 2016;791(9):811–20.
44. Zeki AA, Bratt JM, Rabowsky M, Last LA, Kenyon NJ. Simvastatin inhibits goblet cell hyperplasia and lung arginase in a mouse model of allergic asthma: a novel treatment for airway remodeling? Transl Res. 2010;156(8):335-49.
45. Boskabady MH, Mehrjardi SS, Rezaee A, Rafatpanah H, Jalali S. The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance. J Ethnopharmacol. 2013;150(3):1024-31.
46. Boskabady MH, Shahmohammadi Mehrjardi S, Rezaee A, Rafatpanah H, Jalali S. The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance. Journal of Ethnopharmacology. 2013;150:1024–31.
47. Barnes P. J. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118:3546–56.
48. Boskabady MH, Jalali, S., Farkhondeh, T., and Byrami, G. The extract of Zataria multiflora affect tracheal responsiveness, serum levels of NO, nitrite, PLA2, TP and histamine in sensitized Guinea pigs. J Ethnopharmacol. 2014;156(12):301–8.
49. Keyhanmanesh R, Boskabady MH, Eslamizadeh MJ, Khamneh S, Ebrahimi MA. The effect of thymoquinone, the main constituent of Nigella sativa on tracheal responsiveness and white blood cell count in lung lavage of sensitized guinea pigs. Planta Med. 2010;76(3):218-22.
50. Boskabady MH, Eslamizade, M. J., Tabatabaei, A., Nemati, H., and Mansouri, F. Effect of inhaled fluticasone on lung inflammation administered during and after guinea pig sensitization. Arch Bronconeumol. 2010;46(5):215–22.
51. Nasab EM, Athari SM, Ghafarzade S, Nasab AM, Athari SS. Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma. Allergol Immunopathol (Madr). 2020;48(6):646-53.
52. Jin XH, Li CC, Chen CG, Li SB, Li FX, Gan LH. Relationships of Vascular Endothelial Growth Factor and Interferon-γ, Interleukin-4 in Asthmatic Rats and Effect of Budesonide on Their Expression. Journal of Practical Pediatrics. 2009;24(4):282-4.
53. Robinson D, Hamid Q, Ying S, Bently A, Assoufi B, Durham S, et al. Prednisolone Treatment in Asthma Is Associated with Modulation of Bronchoalveolar Lavage Cell Interleukin-4, Interleukin-5, and Interferon-y Cytokine Gene Expression. Am Rev Respir Dis. 1993;148(5):401-6.
54. Hannuksela ML, Ellahham S. Benefits and risks of sauna bathing. Am J Med. 2001;110(2):118-26.
55. Kunutsor SK, Laukkanen T, Laukkanen JA. Sauna bathing reduces the risk of respiratory diseases: a long-term prospective cohort study. Eur J Epidemiol. 2017;32(12):1107-11.
56. Kunbootsri N, Janyacharoen T, Arrayawichanon P, Chainansamit S, Kanpittaya J, Auvichayapat P, et al. The effect of six-weeks of sauna on treatment autonomic nervous system, peak nasal inspiratory flow and lung functions of allergic rhinitis Thai patients. Asian Pac J Allergy Immunol. 2013;31(2):142-7.
57. Arman Zargaran A, Zarshenas MM, Mehdizadeh A, Mohagheghzadeh A. Oxymel in Medieval Persia. Pharm Hist (Lond) 2012; 42 (1).
58. Bergner P. Oxymel: the forgotten preparation for coughs. Medical Herbalism. 2003;13(3):14-5.
59. Nejatbakhsh F, Karegar-Borzi H, Amin G, Eslaminejad A, Hosseini M, Bozorgi M, et al. Squill Oxymel, a traditional formulation from Drimia Maritima (L.) Stearn, as an add-on treatment in patients with moderate to severe persistent asthma: A pilot, triple-blind, randomized clinical trial. J Ethnopharmacol. 2017;196:186-92.
60. Wang P, Wang X, Yang X, Liu Z, Wu M, Li G. Budesonide suppresses pulmonary antibacterial host defense by down-regulating cathelicidin related antimicrobial peptide in allergic inflammation mice and in lung epithelial cells. BMC Immunology. 2013;14(7).
61. Ernst P, Gonzalez AV, Brassard P, Suissa S. Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. Am J Respir Crit Care Med. 2007;176(2):162–6.
62. Kordafshari G, Mohamadi Kenari H, Nazem E, Moghimi M, Shams Ardakani MR, Keshavarz M, et al. The Role of Nature (Tabiat) in Persian Medicine. Trad Integr Med. 2017;2(4):177-81.
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IssueVol 21 No 2 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v21i2.9221
Keywords
Asthma Persian Medicine Thermotherapy Traditional medicine

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How to Cite
1.
Faryabi R, Vaghasloo M, Athari S, Boskabady M, Zangii B, Kaveh S, Kabiri M. Immunomodulatory Effect of SINA 1.2 Therapy Protocol in Asthmatic Mice Model: A Combination of Oxymel and Sauna. Iran J Allergy Asthma Immunol. 2022;21(2):128-140.