Anti-inflammatory Effect of Boswellia sacra (Franckincense) Essential Oil in a Mouse Model of Allergic Asthma

알러지성 천식 모델 생쥐에서 프랑킨센스 에센셜 오일의 염증 억제 효과

  • Lee, Hye-Youn (Department of Bioengineering Graduate School at Konkuk University) ;
  • Yun, Mi-Young (Department of Beauty Health Care, Daejeon University) ;
  • Kang, Sang-Mo (Department of Bioengineering Graduate School at Konkuk University)
  • 이혜연 (건국대학교 대학원 생물공학과) ;
  • 윤미영 (대전대학교 뷰티건강관리학과) ;
  • 강상모 (건국대학교 대학원 생물공학과)
  • Published : 2008.12.28

Abstract

Frankincense, the gum resin derived from Boswellia species, is complex mixtures composed of about $5{\sim}9%$ highly aromatic essential oil, $65{\sim}85%$ alcohol-soluble resins, and the remaining water-soluble gums. The anti-inflammatory properties of frankincense, alcohole-soluble resins, are well-recognized, but the question of whether aromatic essential oil also plays a role in the allergic asthma remains unanswered. This study was performed to evaluate anti-inflammatory effects of Boswellia sacra essential oil (BSEO) on ovalbumin (OVA)-induced asthma mouse model. BALB/c mice after intraperitoneal OVA sensitization were challenged with intratracheal OVA. One experimental group was inhaled with 0.3% BSEO for the later 8 weeks. BALB/c mice were sensitized and challenged with OVA and developed airway eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. In contrast, the BSEO treated mice had reduced a number of eosinophils among BALF cells, goblet cell hyperplasia, and airway hyperresponsiveness. Cytokine analysis of BALF revealed that BSEO caused an increase in Th1 cytokine (interferon-$\gamma$ (IFN-$\gamma$)) and a decrease in Th2 cytokines (interleukin-4 (IL-4), IL-5 and IL-13) levels. In addition, the OVA-specific serum IgE and eotaxin levels were also reduced. In mice inhaled BSEO, $CD4^+$, $CD3^+/CCR3^+$, and $B220^+/CD23^+$ mediastinal lymph nodes cells were also decreased. These results suggest that inhaled BSEO as a immunomodulator in Th1/Th2 mediated asthma may have therapeutic potential for the treatment in allergic airway inflammation by a simple, cost-effective way.

프랑킨센스는 감람나무 종에서 얻어지는 gum resin으로, 성분은 5-9% 방향정 에센셜 오일, 알코올-용해성인 65-85% resin과 수용성인 gum 잔여물로 구성된 복합물이다. 프랑킨센스의 알코올 용해성인 resin 성분들의 항염증 작용은 잘 알려져 있으나, 방향성 에센셜 오일 성분이 알러지성 천식에 작용을 하는지의 여부는 보고되지 않았다. 실험은 프랑킨센스 에센설 오일(BSEO)이 ovalbumin(OVA)으로 유발된 알러지성 천식 생쥐 모델에 미치는 영향을 조사하기 위해 수행하였다. BALB/c 생쥐는 OVA로 복강감작 후 OVA 기도 투여로 면역반응을 유발시켰다. 실험그룹은 0.3% BSEO를 8주간 흡입시켰다. OVA로 감작, 유발시킨 BALB/c 생쥐에서 기도내 호산구 침윤증가, 점액분비 증가와 기도과민성이 나타났다. 이에 비하여, BSEO 처치군에서 BALF내 호산구수, 술잔세포의 과증식, 기도과민성이 감소되었다. BALF내 사이토카인 분석 결과, BSEO는 Th1 사이토카인인 IFN-$\gamma$를 증가시켰으며 Th2 사이토카인인 IL-4, IL-5와 IL-13을 감소시켰다. 또한, OVA-specific IgE와 eoxtain 분비를 억제시켰다. BSEO 흡입 군에서 종격동 림프절의 $CD4^+$, $CD3^+/CCR3^+$, 및 $B220^+/CD23^+$ 세포들 또한 감소되었다. 이상의 결과에서 BSEO는 Th1/Th2 관여 면역조절인자로 판단되며, BSEO 흡입으로 간단하고 경제적인 방법으로 알러지성 기도 염증 치료가 가능할 것으로 사료되었다.

Keywords

References

  1. Abe, S., N. Maruyama, K. Hayama, H. Ishibashi, S. Inoue, H. Oshima, and H. Yamaguchi. 2003. Suppression of tumor necrosis factor-alpha-induced neutrophil adherence responses by essential oils. Med. Inflamm. 12: 323-328 https://doi.org/10.1080/09629350310001633342
  2. Aronica, M. A., S. McCarthy, S. Swaidani, D. Mitchell, M. Goral, J. R. Sheller, and M. Boothby. 2004. Recall helper T cell response: T helper 1 cell-resistant allergic susceptibility without biasing uncommitted CD4 T cells. Am. J. Respir. Crit. Care Med. 169: 587-595 https://doi.org/10.1164/rccm.200301-100OC
  3. Barnes. P. J. 1999. Effect of bbb2-agonist on inflammatory cells. J. Allergy Clin. Immunol. 104: 10-17 https://doi.org/10.1016/S0091-6749(99)70269-1
  4. Barnes, P. J. 1999. Therapeutic strategy for allergic disease. Nature. 402: B31-38 (Suppl.)
  5. Barnes, P. J. 2000. Endogenous inhibitory mechanisms in asthma. Am. J. Respir. Crit. Care Med. 161: S176-181 https://doi.org/10.1164/ajrccm.161.supplement_2.a1q4-6
  6. Borish, L. 2003. Allergic rhinitis: Systemic inflammation and implications for management. J. Allergy Clin. Immunol. 112: 1021-1031 https://doi.org/10.1016/j.jaci.2003.09.015
  7. Bousquet, J., P. Chanez, J. Y. Lacoste, R. White, P. Vic, P. Godard, and F. B. Michel. 1992. Asthma: a disease remodeling the airways. Allergy. 47: 3-11
  8. Bousquet, J., P. K. Jeffery, W. W. Busse, M. Johnson, and A. M. Vignola. 2000. Asthma, From bronchoconstriction to airway inflammation and remodeling. Am. J. Respir. Crit. Care Med. 161: 1720-1745 https://doi.org/10.1164/ajrccm.161.5.9903102
  9. Bromberg, J. S. 1993. The biology of CD2: adhesion, transmembrane signal, and regulatory receptor of immunity. J. Surg. Res. 54: 258-267 https://doi.org/10.1006/jsre.1993.1041
  10. Busse, W. W., and R. F. Jr. Lemanske. 2001. Asthma. N. Engl. J. Med. 344: 350-362 https://doi.org/10.1056/NEJM200102013440507
  11. Cookson, W. 1999. The alliance of genes and environment in asthma and allergy. Nature. 402: B5-11 (Suppl.)
  12. Coyle, A. J., C. Bertrand, S. Tsuyuki, H. Pircher, S. Walti, G. Le Gros, and F. Erard. 1996. IL-4 differentiates naive CD8+ T cells to a "Th2-like" phenotype: a link between viral infections and bronchial asthma. Ann. N. Y. Acad. Sci. 796: 97-103 https://doi.org/10.1111/j.1749-6632.1996.tb32571.x
  13. Daugherty, B. L., S. J. Siciliano, J. A. DeMartino, L. Malkowitz, and A. Sirotina. 1996. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J. Exp. Med. 183: 2349-2354 https://doi.org/10.1084/jem.183.5.2349
  14. de Heer, H. J., H. Hamida, S. Thomas, J. Danielle, V. Nanda, A. M. W. Monique, C. H. Henk, and N. L. Bart. 2004. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J. Exp. Med. 5: 89-98
  15. de Sousa, A. C., D. S. Alviano, A. F. Blank, P. B. Alves, C. S. Alviano, and C. R. Gattass. 2004. Melissa officinalis L. essential oil: antitumoral and antioxidant activities. J. Pharm. Pharmacol. 56: 677-681 https://doi.org/10.1211/0022357023321
  16. Duan, W., J. H. Chan, C. H. Wonq, B. P. Leung, and W. S. Wonq. 2004. Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. J. Immunol. 172: 7053-7059 https://doi.org/10.4049/jimmunol.172.11.7053
  17. Erin, E. M., T. J. Williams, P. J. Barnes, and T. T. Hansel. 2002. Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. Curr. Drug Targets Inflamm. Allergy. 1: 201-214 https://doi.org/10.2174/1568010023344715
  18. Foster, P. S., S. P. Hogan, A. J. Ramsay, K. I. Mattaei, and I. G. Young. 1996. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J. Exp. Med. 183: 195-201 https://doi.org/10.1084/jem.183.1.195
  19. Garside, P., M. Steel, E. A. Worthey, A. Satoskar, J. Alexander, H. Bluethmann, F. Y. Liew, and A. M. Mowat. 1995. T helper 2 cells are subject to high dose oral tolerance and are not essential for its induction. J. Immunol. 154: 5649-5655
  20. Gleich, G. J. 2000. Mechanisms of eosinophil-associated inflammation. J. Allergy Clin. Immunol. 105: 651-663 https://doi.org/10.1067/mai.2000.105712
  21. Gupta, I., V. Gupta, A. Parihar, S. Gupta, R. Lüdtke, H. Safayhi and H. P. Ammon. 1998. Effect of Boswellia serrata gum resin in patients with bronchial asthma: results of a double blind, placebo-control, 6-week clinical study. Eur. J. Med. Res. 3: 511-514
  22. Hajhashemi, V., A. Ghannadi, and B. Sharif. 2003. Antiinflammatory and analgesic properties of the leaf extracts and essential oil of Lavandula angustifolia Mill. J. Ethnopharmacol. 89: 67-71 https://doi.org/10.1016/S0378-8741(03)00234-4
  23. Hamelmann, E., J. Schwarze, K. Takeda, A. Oshiba, G. L. Larsen, C. G. Irvin, and E. W. Gelfand. 1997. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am. J. Respir. Cirt. Care. Med. 156: 766-775 https://doi.org/10.1164/ajrccm.156.3.9606031
  24. Hamm, S., J. Bleton, J. Connan, and A. Tchapla. 2005. A chemical investigation by headspace SPME and GC-MS of volatile and semi-volatile terpenes in various olibanum samples. Phytochemistry. 66: 1499-1514 https://doi.org/10.1016/j.phytochem.2005.04.025
  25. Hart, P. H., C. Brand, C. F. Carson, T. V. Riley, R. H. Prager, and J. J. Finaly-Jones. 2000. Terpinen-4-ol, the main component of the essential oil of Melalecuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm. Res. 49: 619-626 https://doi.org/10.1007/s000110050639
  26. Huang, M. T., V. Badmaev, Y. Ding, Y. Liu, J. G. Xie, and C. T. Ho. 2000. Anti-tumor and anti-carcinogenic acitivity of triterpenoid, beta boswellic acid. Biofactors. 13: 225-230 https://doi.org/10.1002/biof.5520130135
  27. Jain, V. V., K. Kitaqaki, T. Businqa, I. Hussain, C. Geroge, P. O'shauqhnessy, and J. N. Kline. 2002. CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma. J. Allergy Clin. Immunol. 110: 867-872 https://doi.org/10.1067/mai.2002.129371
  28. Kasakura, S. 1998. A role for T-helper type 1 and type 2 cytokines in the pathogenesis of various human disease. Rinsho. Byori. 46: 915-921
  29. Kay, A. B., S. Ying, and S. R. Durham. 1995. Phenotype of cells positive for interleukin-4 and interleukin-5 mRNA in allergic tissue reaction. Int. Arch. Allergy Immunol. 107: 208-210 https://doi.org/10.1159/000236979
  30. Kibe, A., H. Inoue, S. Fukuyama, K. Machida, K. Matsumoto, H. Koto, T. Ikeqami, H. Aizawa, and N. Hara. 2003. Differential regulation by glucocorticoid of interleukin- 13-induced eosinophilia: hyperresponsiveness, and goblet cell hyperplasia in mouse airways. Am. J. Respir. Crit. Care Med. 167: 50-56 https://doi.org/10.1164/rccm.2110084
  31. Kim, J., H. Lee, Y. Lee, B. G. Oh, C. Cho, Y. Kim, M. Shin, M. Hong, S. K. Jung and H. Bae. 2007. Inhibition effects of Moutan Cortex Radicis on secretion of eotaxin in A549 humna epithelial cells and eosinophil migration. J. Ethnopharmacol. 114: 186-193 https://doi.org/10.1016/j.jep.2007.07.038
  32. Kung, T. T., D. Stelts, J. A. Zurcher, A. S. Watnick, H. Jones, P. J. Mauser, X. Fernandez, S. Umland, and W. Kreutne. 1994. Mechanisms of allergic pulmonary eosinophilia in the mouse. J. Allergy Clin. Immunol. 94: 1217-1224 https://doi.org/10.1016/0091-6749(94)90335-2
  33. Larché, M., D. S. Robinson, and A. B. Kay. 2002. The role of T lymphocytes in the pathogenesis of asthma. J. Allergy Clin. Immunol. 111: 450-463
  34. Makino, S., and T. Fukuda. 1995. Eosinophils and allergy in asthma. Allergy Proc. 16: 13-21
  35. Marco, I., H. Hamida, M. van Nimwegen, K. Mirjam, V. Nanda, C. H. Henk, and N. L. Bart. 2006. Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function. J. Clin. Invest. 116: 2935-2944 https://doi.org/10.1172/JCI28295
  36. Maruyama, N., Y. Sekimoto, H. Ishibashi, S. Inouye, H. Oshima, H. Yamaquchi, and S. Abe. 2005. Suppression of neutrophil accumulation in mice by cutaneous application of geranium essential oil. J. Inflamm. (Lond). 2: 1-11 https://doi.org/10.1186/1476-9255-2-1
  37. Marx, J., E. Pretorius, and M. J. Bester. 2006. Effects of Urginea sanguinea, a traditional asthma remedy, on embryo neuronal development. J. Ethnopharmacol. 104: 315-321 https://doi.org/10.1016/j.jep.2005.09.022
  38. Palmerio, E. M., R. J. Hopp, R. E. Biven, A. K. Bewtra, N. N. Nair, and R. G. Townley. 1992. Probability of asthma based on methacholine challenge. Chest. 101: 630-633 https://doi.org/10.1378/chest.101.3.630
  39. Paul, J. B., G. Raif, and C. O. Hans. 2003. Desloratadine inhibits allergen-induced airway inflammation and bronchial hyperresponsiveness and alters T-cell responses in murine models of asthma. J. Allergy Clin. Immunol. 112: 149-159 https://doi.org/10.1067/mai.2003.1616
  40. Ram, A., U. Mabalirajan, M. Das, I. Bhattacharya, A. K. Dinda, S. V. Ganqal and B. Ghosh. 2006. Glycyrrhizin alleviates experimental allergic asthma in mice. Int. Immunopharmacol. 6: 1468-1477 https://doi.org/10.1016/j.intimp.2006.04.020
  41. Redington, A. E., and P. H. Howarth. Airway wall remodeling in asthma. Thorax. 52: 310-312 https://doi.org/10.1136/thx.52.4.310
  42. Robinson, D. S., Q. Hamid, S. Ying, A. Tsicopoulos, J. Barkans, A. M. Bentley, C. Corrigan, S. R. Durham, and A. B. Kay. 1992. Predominant Th2-like bronchoalveolar Tlymphocyte population in atopic asthma. N. Engl. J. Med. 326: 298-304 https://doi.org/10.1056/NEJM199201303260504
  43. Roche, W. R., R. Beasley, J. H. Wiliams, and S. T. Holgate. 1989. Subepithelial fibrosis in the bronchi of asthmatics. Lancet. 1: 520-524
  44. Roh, G. S., S. W. Seo, S. Yeo, J. M. Lee, J. W. Choi, E. Kim, Y. Shin, C. Cho, H. Bae, S. K. Jung, and K. Kwack. 2005. Efficacy of a traditional Korean medicine, Chung-Sang-Bo- Ha-Tang, in a murine model of chronic asthma. Int. Immunopharmacol. 5: 427-436 https://doi.org/10.1016/j.intimp.2004.09.036
  45. Roitt, I. M., J. Brostoff, and D. Male. 1989. Immunology. pp. 11-20. 2nd ed. Gower medical Publishing, London
  46. Roy, S., S. Khanna, H. Shah, C. Rink, C. Phillips, H. Preuss, G. V. Subbaraju, G. Trimurtulu, A. V. Krishnaraju, M. Baqchi, D. Baqchi, and C. K. Sen. 2005. Human genome screen to identify the genetic basis of the anti-inflammatory effects of Boswellia in microvascular endothelial cells. DNA Cell Biol. 24: 244-255 https://doi.org/10.1089/dna.2005.24.244
  47. Scola, A. M., L. K. Chong, S. K. Suvarna, R. Chess-Williams, and P. T. Peachell. 2004. Desensitisation of mast cell beta2- adrenorceptor-mediated responses by salmeterol and formoterol. Br. J. Pharmacol. 141: 163-171 https://doi.org/10.1038/sj.bjp.0705599
  48. Sharma, M. L., A. Kaul, A., Khajuria, S. Singh, and G. B. Singh. 1996. Immunomodulatory activity of boswellic acids (pentacyclic triterpene acids) from Boswellia serrata. Phytother. Res. 10: 107-112 https://doi.org/10.1002/(SICI)1099-1573(199603)10:2<107::AID-PTR780>3.0.CO;2-3
  49. Singh, G. B., S. Singh, and S. Bani. 1996. Anti-inflammatroy actions of boswellic acids. Phytomedicine 3: 81-85 https://doi.org/10.1016/S0944-7113(96)80017-1
  50. Takami, M., Y. Takata, K. Matsumoto, S. Ono, and W. Tsukada. 1991. Effects of DP-1904, a new thromboxane A2 synthetase inhibitor, on guinea pig experimental asthma. Ann. N. Y. Acad. Sc. 629: 407-409 https://doi.org/10.1111/j.1749-6632.1991.tb37999.x
  51. Takayuki, N., A. Yumiko, E. Michiko, N. Shin-yu, Y. Takeshi, and Y. Haruki. 2004. Anti-allergic acitivity of a Kampho (Japanese herbal) medicine "Sho-seiryu-to (Xiao- Qing-Long-Tang)" on airway inflammation in a mouse model. Int. Immunopharmacol. 4: 1353-1365 https://doi.org/10.1016/j.intimp.2004.05.021
  52. Taube, C., C. Duez, Z. H. Cui, K. Takeda, Y. H. Rha, J. W. Park, A. Balhorn, D. D. Donaldson, A. Dakhama, and E. W. Gelfand. 2002. The role of IL-13 in established allergic airway disease. J. Immunol. 169: 6482-6489 https://doi.org/10.4049/jimmunol.169.11.6482
  53. Y., M. Dohi, R. Tanaka, A. Sato, K. Nakaqome, and K. Yamamoto. 2001. Early interleukin 4-dependent response can induce ariway hyperreactivity before development of airway inflammation in a mouse model of asthma. Lab. Invest. 81: 1385-1396 https://doi.org/10.1038/labinvest.3780352
  54. Tucker, A. O., 1986. Frankincense and myrrh. Econ. Bot. 40: 425-433 https://doi.org/10.1007/BF02859654
  55. van Schayck, C. P., I. D. Bijl-Hofland, S. G. Cloosterman, H. T. Folqering, F. J. vad der Elshout, and C. Van Weel. 2002. Potential masking effect on dyspnoea perception by shortand long-acting beta2-agonists in asthma. Eur. Respir. J. 19: 240-245 https://doi.org/10.1183/09031936.02.00203602
  56. Vignola, A. M., P. Chanez, A. M. Campbell, F. Souques, B. Lebel, I. Enander, and J. Bousquet. 1998. Airway inflammation in mild intermittent and in persistent asthma. Am. J. Respir. Crit. Care Med. 157: 403-409 https://doi.org/10.1164/ajrccm.157.2.96-08040
  57. Walker, C., E. Bode, L. Boer, T. T. Hansel, K. Blaser, J. C. Jr. Virchow. 1992. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveloar lavage. Am. Rev. Respir. Dis. 146: 109-115 https://doi.org/10.1164/ajrccm/146.1.109
  58. Won, J., Y. G. Hur, E. M. Hur, S. H. Park, M. A. Kang, Y. Choi, C. Park, K. H. Lee, and Y. Yun. 2003. Rosmarinic acid inhibits TCR-induced T cell activation and proliferation in an Lck-dependent manner. Eur. J. Immunol. 33: 870-879 https://doi.org/10.1002/eji.200323010
  59. Yang, M., S. P. Hogan, S. Mahalingam, S. M. Pope, N. Zimmermann, P. Fulkerson, L. A. Dent, I. G. Young, K. I. Mattaei, M. E. Rothenberg, and P. S. Foster. 2003. Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity. J. Allergy. Clin. Immunol. 112: 935-943 https://doi.org/10.1016/j.jaci.2003.08.010
  60. Yang, S. H., C. Y. Hong, and C. L. Yu. 2001. Decreased serum IgE level, decreased IFN-r and IL-5 but increased IL- 10 production, and suppressed cyclooxygenase 2 mRNA expression in patients with perennial allergic rhinitis after treatment with a new mixed formula of Chinese herbs. Int. Immunopharmacol. 1: 1173-1182 https://doi.org/10.1016/S1567-5769(01)00051-0