Skip to main content

Advertisement

Log in

Effect of (-)-α-Bisabolol on the Inflammatory Response in Systemic Infection Experimental Model in C57BL/6 Mice

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

(-)-α-Bisabolol (BISA) is an unsaturated monocyclic sesquiterpenes compound, mainly found in the essential oil of chamomile (Matricaria chamomilla). It has been reported that this compound has several biological activities, but there are few studies evaluating the activity of this compound in the systemic inflammatory response in infectious processes. The aim of this study was to evaluate the effect of BISA on the inflammatory response and survival rate in a systemic infection model, and in vitro neutrophils phagocytic activity. BISA at concentration of 3, 10, 30, and 90 μg/ml did not presented in vitro cytotoxicity in MTT assay, and at concentrations of 1 and 3 μg/ml the BISA treatment increased in vitro phagocytic neutrophil activity. For the inflammatory response study, we verified the BISA treatment effect in a cecal ligation and puncture (CLP)-induced systemic infection model in mice; in this model, we demonstrate that BISA at dose of 100 mg/kg reduced the leukocyte recruitment in peritoneal cavity; at dose of 200 mg/kg, the NO concentration was increased in the peritoneal cavity. The bacteria CFU number was reduced in mice blood in the BISA treatment, at doses of 100 and 200 mg/kg. The BISA treatment at doses of 50 and 100 mg/kg increased the myeloperoxidase activity and reduction NO production in lung tissue of mice in CLP model. At dose of 100 mg/kg, the BISA treatment was able to reduce the mortality rate of mice submitted to CLP-induced sepsis and observed for 7 days. The results suggest an effect of BISA on inflammatory response, with activity on leukocyte chemotactic and NO production, in addition to increasing the survival rate of animals submitted to CLP model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Andrade, S.F., L.G.V. Cardoso, J.C.T. Carvalho, and J.K. Bastos. 2007. Anti-inflammatory and antinociceptive activities of extract, fractions and populnoic acid from bark wood of Austroplenckia populnea. Journal of Ethnopharmacology 109: 464–471. https://doi.org/10.1016/j.jep.2006.08.023.

    Article  CAS  PubMed  Google Scholar 

  2. Aderem, A., and R.J. Ulevitch. 2000. Toll-like receptors in the induction of the innate immune response. Nature 406: 782–787. https://doi.org/10.1038/35021228.

    Article  CAS  PubMed  Google Scholar 

  3. Buckley, Christopher D., D.W. Gilroy, and C.N. Serhan. 2014. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40: 315–327. https://doi.org/10.1016/j.immuni.2014.02.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Franceschi, C., and J. Campisi. 2014. Chronic inflammation (Inflammaging) and its potential contribution to age-associated diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 69: S4–S9. https://doi.org/10.1093/gerona/glu057.

    Article  Google Scholar 

  5. Araújo, C.V., V. Estato, E. Tibiriçá, P.T. Bozza, H.C. Castro-Faria-Neto, and A.R. Silva. 2012. PPAR gamma activation protects the brain against microvascular dysfunction in sepsis. Microvascular Research 84: 218–221. https://doi.org/10.1016/j.mvr.2012.05.006.

    Article  CAS  PubMed  Google Scholar 

  6. Akdis, M., A. Aab, C. Altunbulakli, K. Azkur, R.A. Costa, R. Crameri, S. Duan, T. Eiwegger, A. Eljaszewicz, R. Ferstl, R. Frei, M. Garbani, A. Globinska, L. Hess, C. Huitema, T. Kubo, Z. Komlosi, P. Konieczna, N. Kovacs, U.C. Kucuksezer, N. Meyer, H. Morita, J. Olzhausen, L. O'Mahony, M. Pezer, M. Prati, A. Rebane, C. Rhyner, A. Rinaldi, M. Sokolowska, B. Stanic, K. Sugita, A. Treis, W. van de Veen, K. Wanke, M. Wawrzyniak, P. Wawrzyniak, O.F. Wirz, J.S. Zakzuk, and C.A. Akdis. 2016. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. Journal of Allergy and Clinical Immunology 138: 984–1010. https://doi.org/10.1016/j.jaci.2016.06.033.

    Article  CAS  PubMed  Google Scholar 

  7. Rocha, N.F.M., E.T. Venâncio, B.A. Moura, M.I.G. Silva, M.R.A. Neto, E.R.V. Rios, D.P. Sousa, S.M.M. Vasconcelos, M.M.F. Fonteles, and F.C.F. Sousa. 2010. Gastroprotection of (-)-alpha-bisabolol on acute gastric mucosal lesions in mice: the possible involved pharmacological mechanisms. Fundamental & Clinical Pharmacology 24: 63–71. https://doi.org/10.1111/j.1472-8206.2009.00726.x.

    Article  CAS  Google Scholar 

  8. McAndrew, B.A. 1992. Sesquiterpenoids: the lost dimension of perfumery. Perfumer Flavorist 17: 1–12.

    CAS  Google Scholar 

  9. Forrer, M., E.M. Kulik, A. Filippi, and T. Waltimo. 2013. The antimicrobial activity of alpha-bisabolol and tea tree oil against Solobacterium moorei, a Gram-positive bacterium associated with halitosis. Archives of Oral Biology 58: 10–16. https://doi.org/10.1016/j.archoralbio.2012.08.001.

    Article  CAS  PubMed  Google Scholar 

  10. Braga, P.C., M. Dal Sasso, E. Fonti, and M. Culici. 2009. Antioxidant activity of bisabolol: inhibitory effects on chemiluminescence of human neutrophil bursts and cell-free systems. Pharmacology 83: 110–115. https://doi.org/10.1159/000186049.

    Article  CAS  PubMed  Google Scholar 

  11. Gomes-Carneiro, M.R., D.M.M. Dias, A.C.A.X. De-Oliveira, and F.J.R. Paumgartten. 2005. Evaluation of mutagenic and antimutagenic activities of α-bisabolol in the Salmonella/microsome assay. Mutation Research, Genetic Toxicology and Environmental Mutagenesis 585: 105–112. https://doi.org/10.1016/j.mrgentox.2005.04.007.

    Article  CAS  Google Scholar 

  12. Vila, R., A.I. Santana, R. Pérez-Rosés, A. Valderrama, M.V. Castelli, S. Mendonca, S. Zacchino, M.P. Gupta, and S. Cañigueral. 2010. Composition and biological activity of the essential oil from leaves of Plinia cerrocampanensis, a new source of alpha-bisabolol. Bioresource Technology 101: 2510–2514. https://doi.org/10.1016/j.biortech.2009.11.021.

    Article  CAS  PubMed  Google Scholar 

  13. Rocha, N.F.M., E.R.V. Rios, A.M.R. Carvalho, G.S. Cerqueira, A.A. Lopes, L.K.A.M. Leal, M.L. Dias, D.P. Sousa, and F.C.F. Sousa. 2011. Anti-nociceptive and anti-inflammatory activities of (−)-α-bisabolol in rodents. Naunyn-Schmiedeberg's Archives of Pharmacology 384: 525–533. https://doi.org/10.1007/s00210-011-0679-x.

    Article  CAS  PubMed  Google Scholar 

  14. Bezerra, S.B., L.K.A.M. Leal, N.A.P. Nogueira, N.A.N. Pinto, and A.R. Campos. 2009. Bisabolol-induced gastroprotection against acute gastric lesions: role of prostaglandins, nitric oxide, and KATP+ channels. Journal of Medicinal Food 12: 1403–1406. https://doi.org/10.1089/jmf.2008.0290.

    Article  CAS  PubMed  Google Scholar 

  15. Maurya, A.K., M. Singh, V. Dubey, S. Srivastava, S. Luqman, and D.U. Bawankule. 2014. α-(-)-bisabolol reduces pro-inflammatory cytokine production and ameliorates skin inflammation. Current Pharmaceutical Biotechnology 15: 173–181.

    Article  CAS  Google Scholar 

  16. Sun, L., H. Zhang, L. Zhi, Q. Wen, Z. Qi, S. Yan, W. Li, and G. Zhang. 2017. Bisabolol attenuates sepsis-induced acute lung injury through inhibiting NF-κB-mediated inflammatory response. International Journal of Clinical and Experimental Pathology 10: 1052–1062.

    CAS  Google Scholar 

  17. Budavari, S. 1996. The Merck index : an encyclopedia of chemicals, drugs, and biologicals. 12th ed. Whitehouse Station.

  18. Silva-Filho, S.E., L.A.M. Wiirzler, H.A.O. Cavalcante, N.S. Uchida, F.M.S. Silva-Comar, G.F.E. Cardia, E.L. da Silva, R.P. Aguiar, C.A. Bersani-Amado, and R.K.N. Cuman. 2016. Effect of patchouli (Pogostemon cablin) essential oil on in vitro and in vivo leukocytes behavior in acute inflammatory response. Biomedicine and Pharmacotherapy 84. https://doi.org/10.1016/j.biopha.2016.10.084.

    Article  CAS  Google Scholar 

  19. Rittirsch, D., M.S. Huber-Lang, M.A. Flierl, and P.A. Ward. 2008. Immunodesign of experimental sepsis by cecal ligation and puncture. Nature Protocols 4: 31–36. https://doi.org/10.1038/nprot.2008.214.

    Article  CAS  Google Scholar 

  20. Freitas, J.C.O.C., A.C. Medeiros, and V.S.F. Sales. 2004. Proteção pela glucana em modelo experimental de sepse. Acta Cirúrgica Brasileira 19: 296–307. https://doi.org/10.1590/S0102-86502004000300012.

    Article  Google Scholar 

  21. Maciel, M.C.G., J.C. Farias, M.J. Maluf, E.A. Gomes, P.V.S. Pereira, W.C. Aragão-Filho, J.B. Frazão, C.G. Costa, S.M. Sousa, L.A. Silva, Flávia M.M. Amaral, M. Russo, R.N.M. Guerra, and F.R.F. Nascimento. 2008. Syzygium jambolanum treatment improves survival in lethal sepsis induced in mice. BMC Complementary and Alternative Medicine 8: 57–57. https://doi.org/10.1186/1472-6882-8-57.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Benjamim, C.F. 2001. Atualização sobre mediadores e modelos experimentais de sepse. Medicina 34: 18–26.

    Google Scholar 

  23. Newham, P., D. Ross, P. Ceuppens, S. Das, J.W.T. Yates, C. Betts, J. Reens, K.J. Randall, R. Knight, and J.S. McKay. 2014. Determination of the safety and efficacy of therapeutic neutralization of tumor necrosis factor-α (TNF-α) using AZD9773, an anti-TNF-α immune Fab, in murine CLP sepsis. Inflammation Research 63: 149–160. https://doi.org/10.1007/s00011-013-0683-3.

    Article  CAS  PubMed  Google Scholar 

  24. Kuo, M.C., C.Y. Chang, T.S. Cheng, and M.J. Wu. 2008. Immunomodulatory effect of Antrodia camphorata mycelia and culture filtrate. Journal of Ethnopharmacology 120: 196–203. https://doi.org/10.1016/j.jep.2008.08.011.

    Article  PubMed  Google Scholar 

  25. Amulic, B., C. Cazalet, G.L. Hayes, K.D. Metzler, and A. Zychlinsky. 2012. Neutrophil Function: From Mechanisms to Disease. Annual Review of Immunology 30: 459–489. https://doi.org/10.1146/annurev-immunol-020711-074942.

    Article  CAS  PubMed  Google Scholar 

  26. Ritter, C., M. Andrades, A. Reinke, J.C.F. Moreira, and F. Dal-Pizzol. 2004. Drug intervention trials in sepsis. The Lancet 364: 498. https://doi.org/10.1016/S0140-6736(04)16799-8.

    Article  Google Scholar 

  27. Ziaja, M. 2012. Sepsis and septic encephalopathy: characteristics and experimental models. Folia Neuropathologica 50: 231–239.

    Article  CAS  Google Scholar 

  28. Michels, M., A.S. Vieira, F. Vuolo, H.G. Zapelini, B. Mendonça, F. Mina, D. Dominguini, A. Steckert, P.F. Schuck, J. Quevedo, F. Petronilho, and F. Dal-Pizzol. 2015. The role of microglia activation in the development of sepsis-induced long-term cognitive impairment. Brain, Behavior, and Immunity 43: 54–59. https://doi.org/10.1016/j.bbi.2014.07.002.

    Article  CAS  PubMed  Google Scholar 

  29. Mina, F., C.M. Comim, D. Dominguini, O.J. Cassol-Jr, D.M. Dall’Igna, G.K. Ferreira, M.C. Silva, L.S. Galant, E.L. Streck, J. Quevedo, and F. Dal-Pizzol. 2014. Il1-β Involvement in Cognitive Impairment after Sepsis. Molecular Neurobiology 49: 1069–1076. https://doi.org/10.1007/s12035-013-8581-9.

    Article  CAS  PubMed  Google Scholar 

  30. Blackwell, T.S., and J.W. Christman. 1996. Sepsis and cytokines: current status. British Journal of Anaesthesia 77: 110–117.

    Article  CAS  Google Scholar 

  31. Kim, S., E. Jung, J.H. Kim, Y.H. Park, J. Lee, and D. Park. 2011. Inhibitory effects of (−)-α-bisabolol on LPS-induced inflammatory response in RAW264.7 macrophages. Food and Chemical Toxicology 49: 2580–2585. https://doi.org/10.1016/j.fct.2011.06.076.

    Article  CAS  PubMed  Google Scholar 

  32. Korhonen, L., I. Hansson, J.P. Kukkonen, K. Brännvall, M. Kobayashi, K. Takamatsu, and D. Lindholm. 2005. Hippocalcin protects against caspase-12-induced and age-dependent neuronal degeneration. Molecular and Cellular Neurosciences 28: 85–95. https://doi.org/10.1016/j.mcn.2004.08.015.

    Article  CAS  PubMed  Google Scholar 

  33. Clancy, R.M., A.R. Amin, and S.B. Abramson. 1998. The role of nitric oxide in inflammation and immunity. Arthritis and Rheumatism 41: 1141–1151. https://doi.org/10.1002/1529-0131(199807)41:7<1141::AID-ART2>3.0.CO;2-S.

    Article  CAS  PubMed  Google Scholar 

  34. Atzler, D., E. Schwedhelm, and C.U. Choe. 2015. L-Homoarginine and cardiovascular disease. Current Opinion in Clinical Nutrition and Metabolic Care 18: 83–88. https://doi.org/10.1097/MCO.0000000000000123.

    Article  CAS  PubMed  Google Scholar 

  35. Kirkeboen, K.A., and O.A. Strand. 1999. The role of nitric oxide in sepsis—an overview. Acta Anaesthesiologica Scandinavica 43: 275–288. https://doi.org/10.1034/j.1399-6576.1999.430307.x.

    Article  CAS  PubMed  Google Scholar 

  36. Taysi, S., Z. Umudum, R.A. Sari, S. Kuskay, and N. Bakan. 2003. Nitric oxide level and superoxide dismutase activity in serum of patients with rheumatoid arthritis. The Pain Clinic 15: 429–434. https://doi.org/10.1163/156856903770196818.

    Article  Google Scholar 

  37. Van Dervort, A.L., L. Yan, P.J. Madara, J.P. Cobb, R.A. Wesley, C.C. Corriveau, M.M. Tropea, and R.L. Danner. 1994. Nitric oxide regulates endotoxin-induced TNF-alpha production by human neutrophils. Journal of Immunology 152: 4102–4109.

    Google Scholar 

  38. Fukatsu, K., H. Saito, I. Han, S. Furukawa, M.T. Lin, T. Matsuda, S. Ikeda, T. Inoue, H. Yasuhara, and T. Muto. 1998. Nitric oxide donor decreases neutrophil adhesion in both lung and peritoneum during peritonitis. The Journal of Surgical Research 74: 119–124. https://doi.org/10.1006/jsre.1997.5234.

    Article  CAS  PubMed  Google Scholar 

  39. Xie, C.Y., W. Yang, J. Ying, Q.C. Ni, X.D. Pan, J.H. Dong, K. Li, and X.S. Wang. 2011. B-cell lymphoma-2 over-expression protects δ-elemene-induced apoptosis in human lung carcinoma mucoepidermoid cells via a nuclear factor kappa B-related pathway. Biological and Pharmaceutical Bulletin 34: 1279–1286.

    Article  CAS  Google Scholar 

  40. Manuele, M.G., M.L.B. Arcos, R. Davicino, G. Ferraro, G. Cremaschi, and C. Anesini. 2009. Limonene exerts antiproliferative effects and increases nitric oxide levels on a lymphoma cell line by dual mechanism of the ERK pathway: relationship with oxidative stress. Cancer Investigation 28: 135–145. https://doi.org/10.3109/07357900903179583.

    Article  Google Scholar 

  41. Qi, J., N. Li, J.H. Zhou, B.Y. Yu, and S.X. Qiu. 2010. Isolation and anti-inflammatory activity evaluation of triterpenoids and a monoterpenoid glycoside from Harpagophytum procumbens. Planta Medica 76: 1892–1896. https://doi.org/10.1055/s-0030-1250029.

    Article  CAS  PubMed  Google Scholar 

  42. Thimmulappa, R.K., R.J. Fuchs, D. Malhotra, C. Scollick, K. Traore, J.H. Bream, M.A. Trush, K.T. Liby, M.B. Sporn, T.W. Kensler, and S. Biswal. 2007. Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils. Antioxidants & Redox Signaling 9: 1963–1970. https://doi.org/10.1089/ars.2007.1745.

    Article  CAS  Google Scholar 

  43. Dulhunty, J.M., J.A. Roberts, J.S. Davis, S.A.R. Webb, R. Bellomo, C. Gomersall, C. Shirwadkar, G.M. Eastwood, J. Myburgh, D.L. Paterson, and J. Lipman. 2013. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clinical Infectious Diseases 56: 236–244. https://doi.org/10.1093/cid/cis856.

    Article  CAS  PubMed  Google Scholar 

  44. Pedro, T.C.S., A.M. Morcillo, and E.C.E. Baracat. 2015. Etiology and prognostic factors of sepsis among children and adolescents admitted to the intensive care unit. Revista Brasileira de Terapia Intensiva: 27. https://doi.org/10.5935/0103-507X.20150044.

  45. Bradley, P.P., D.A. Priebat, R.D. Christensen, and G. Rothstein. 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. The Journal of Investigative Dermatology 78: 206–209.

    Article  CAS  Google Scholar 

  46. Huang, J., A. Milton, R.D. Arnold, H. Huang, F. Smith, J.R. Panizzi, and P. Panizzi. 2016. Methods for measuring myeloperoxidase activity toward assessing inhibitor efficacy in living systems. Journal of Leukocyte Biology 99: 541–548. https://doi.org/10.1189/jlb.3RU0615-256R.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mathias, J.R., B.J. Perrin, T.X. Liu, J. Kanki, A.T. Look, and A. Huttenlocher. 2006. Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish. Journal of Leukocyte Biology 80: 1281–1288. https://doi.org/10.1189/jlb.0506346.

    Article  CAS  PubMed  Google Scholar 

  48. Osborn, L. 1990. Leukocyte adhesion to endothelium in inflammation. Cell 62: 3–6. https://doi.org/10.1016/0092-8674(90)90230-C.

    Article  CAS  PubMed  Google Scholar 

  49. Hogg, J.C., and C.M. Doerschuk. 1995. Leukocyte Traffic in the Lung. Annual Review of Physiology 57: 97–114. https://doi.org/10.1146/annurev.ph.57.030195.000525.

    Article  CAS  PubMed  Google Scholar 

  50. Lien, D.C., W.W. Wagner, R.L. Capen, C. Haslett, W.L. Hanson, S.E. Hofmeister, P.M. Henson, and G.S. Worthen. 1987. Physiological neutrophil sequestration in the lung: visual evidence for localization in capillaries. Journal of applied physiology (Bethesda, Md. : 1985) 62: 1236–1243.

    Article  CAS  Google Scholar 

  51. Deshmane, S.L., S. Kremlev, S. Amini, and B.E. Sawaya. 2009. Monocyte chemoattractant protein-1 (MCP-1): an overview. Journal of Interferon & Cytokine Research 29: 313–326. https://doi.org/10.1089/jir.2008.0027.

    Article  CAS  Google Scholar 

  52. Speyer, C.L., H. Gao, N.J. Rancilio, T.A. Neff, G.B. Huffnagle, J.V. Sarma, and P.A. Ward. 2004. Novel chemokine responsiveness and mobilization of neutrophils during sepsis. The American Journal of Pathology 165: 2187–2196. https://doi.org/10.1016/S0002-9440(10)63268-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Jailson Araujo Dantas and Celia Regina Miranda for technical assistance. This study was supported by grants from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Saulo Euclides Silva-Filho.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cavalcante, H.A.O., Silva-Filho, S.E., Wiirzler, L.A.M. et al. Effect of (-)-α-Bisabolol on the Inflammatory Response in Systemic Infection Experimental Model in C57BL/6 Mice. Inflammation 43, 193–203 (2020). https://doi.org/10.1007/s10753-019-01109-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-019-01109-8

KEY WORDS

Navigation