Systemic Administration of Rosmarinus officinalis Attenuates the Inflammatory Response Induced by Carrageenan in the Mouse Model of Pleurisy

Abstract

Rosmarinus officinalis, also named rosemary, is a native plant from the Mediterranean region that is useful for the treatment of inflammatory diseases. Studies using experimental models and/or in vitro tests have shown the important biological effects of rosemary. In this context, the mechanism of the anti-inflammatory activity of rosemary must be investigated to support the discovery of new substances with anti-inflammatory effects. The aim of the present study was to investigate the anti-inflammatory effects of crude extract oil free obtained from the leaves of rosemary in an animal model of inflammation, thus evaluating its medicinal use for the treatment of inflammatory conditions. Also its ethanol, hexane, and ethyl acetate fractions, as well as its isolated compounds carnosol and rosmarinic acid were analyzed. Swiss mice were used for the in vivo experiments. The effect of this herb on the inhibition of the leukocytes, exudation, myeloperoxidase, and adenosine-deaminase activities, nitrite/nitrate, interleukin 17A, and interleukin 10 levels and mRNA expression was determined. The crude extract and its derived fractions, in addition to its isolated compounds, inhibited leukocytes and decreased exudation and myeloperoxidase and adenosine-deaminase activities, as well as nitrite/nitrate and interleukin 17A levels and mRNA expression, besides increasing interleukin 10 levels and mRNA expression. Rosemary showed important anti-inflammatory activity by inhibiting leukocytes and decreasing exudation. These effects were associated with a decrease in the proinflammatory parameters (myeloperoxidase, adenosine-deaminase, nitrite/nitrate, and interleukin 17A) and an increase in the anti-inflammatory cytokine (interleukin 10). This study confirms the anti-inflammatory properties of rosemary and validates its use in folk medicine to treat inflammatory diseases such as rheumatism and asthma.

Key words

anti-inflammatory effects - cytokines - mouse model of pleurisy - Rosmarinus officinalis - Lamiaceae

• References

• 1 Saklani A, Kutty SK. Plant-derived compounds in clinical trials. Drug Discov Today 2008; 13: 161-171
• 2 Potterat O, Hamburger M. Drug discovery and development with plant-derived compounds. Prog Drug Res 2008; 45: 47-118
• 3 Gosslau A, Li S, Ho C, Chen KY, Rawson NE. The importance of natural product characterization in studies of their anti-inflammatory activity. Mol Nutr Food Res 2011; 55: 74-82
• 4 Albuquerque UP, Medeiros PM, Almeida ALS, Monteiro JM, Neto EMFL, Melo JG, Santos JP. Medicinal plants of the caatinga (semi-arid) vegetation of NE Brazil: a quantitative approach. J Ethnopharmacol 2007; 114: 325-354
• 5 Ulbricht C, Abrams TR, Brigham A, Ceurvels J, Clubb J, Curtiss W, Kirkwood CD, Giese N, Hoehn K, Iovin R, Isaac R, Rusie E, Serrano JMG, Varghese M, Weissner W, Regina C, Windsor RC. An evidence-based systematic review of rosemary (Rosmarinus officinalis) by the Natural Standard Research Collaboration. J Diet Suppl 2010; 7: 351-413
• 6 Petersen M, Abdullah Y, Benner J, Eberle D, Gehlen K, Hücherig S, Janiak V, Kim KH, Sander M, Weitzel C, Wolters S. Evolution of rosmarinic acid biosynthesis. Phytochemistry 2009; 70: 1663-1679
• 7 Ngo SNT, Williams DB, Head RJ. Rosemary and cancer prevention: preclinical perspectives. Crit Rev Food Sci Nutr 2011; 51: 946-954
• 8 Kontogianni AVG, Tomic G, Nikolic I, Nerantzaki AA, Sayyad N, Stosic-Grujicic S, Stojanovic I, Gerothanassis IP, Tzakos AG. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chem 2013; 136: 120-129
• 9 Bakirel T, Bakirel U, Keles OU, Ulgen SG, Yardibi H. In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits. J Ethnopharmacol 2008; 116: 64-73
• 10 Machado DG, Bettio LEB, Cunha MP, Capra JC, Dalmarco JB, Pizzolatti MG, Rodrigues ALS. Antidepressant-like effect of the extract of Rosmarinus officinalis in mice: involvement of the monoaminergic system. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 642-650
• 11 Ibarra A, Cases J, Bily A, He K, Bai N, Roller M, Coussaert A, Ripoll C. Importance of extract standardization and in vitro/ex vivo assay selection for the evaluation of antioxidant activity of botanicals: a case study on three Rosmarinus officinalis L. extracts. J Med Food 2010; 13: 1167-1175
• 12 González-Trujano ME, Peña EI, Martínez AL, Moreno J, Guevara-Fefer P, Déciga-Campos M, López-Muñoz FJ. Evaluation of the antinociceptive effect of Rosmarinus officinalis L. using three different experimental models in rodents. J Ethnopharmacol 2007; 111: 476-482
• 13 Takaki I, Bersani-Amado LE, Vendruscolo A, Sartoretto SM, Diniz SP, Bersani-Amado CA, Cuman RK. Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models. J Med Food 2008; 11: 741-746
• 14 Tai J, Cheung S, Wu M, Hasman D. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro . Phytomedicine 2012; 19: 436-443
• 15 Ventura-Martínez R, Rivero-Osorno O, Gómez C, González-Trujano ME. Spasmolytic activity of Rosmarinus officinalis L. involves calcium channels in the guinea pig ileum. J Ethnopharmacol 2011; 137: 1528-1532
• 16 Amin A, Hamza AA. Hepatoprotective effects of Hibiscus, Rosmarinus, and Salvia on azathioprine-induced toxicity in rats. Life Sci 2005; 77: 266-278
• 17 Park SE, Kim S, Sapkota K, Kim SJ. Neuroprotective effect of Rosmarinus officinalis extract on human dopaminergic cell line, SH-SY5Y. Cell Mol Neurobiol 2010; 30: 759-767
• 18 Altinier G, Sosa S, Aquino RP, Mencherini T, Della LR, Tubaro A. Characterization of topical anti-inflammatory compounds in Rosmarinus officinalis L. J Agric Food Chem 2007; 55: 1718-1723
• 19 Benincá JP, Dalmarco JB, Pizzolatti MG, Fröde TS. Analysis of the anti-inflammatory properties of Rosmarinus officinalis L. in mice. Food Chem 2011; 124: 468-475
• 20 Mengoni ES, Vichera G, Rigano LA, Rodriguez-Puebla ML, Galliano SR, Cafferata EE, Pivetta OH, Moreno S, Vojnov AA. Suppression of COX-2, IL-1β and TNF-α expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia 2011; 82: 414-421
• 21 Fröde TS, Medeiros YS. Myeloperoxidase and adenosinedeaminase levels in the pleural fluid leakage induced by carrageenan in the mouse model of pleurisy. Mediators Inflamm 2001; 10: 223-227
• 22 Malle E, Furtmüller PG, Satttler W, Obinger C. Myeloperoxidase: a target for new drug development?. Br J of Pharmacol 2007; 152: 838-854
• 23 Van Der Veen BS, Winther MPJ, Heeringa P. Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease. Antioxid Redox Signal 2009; 11: 1-39
• 24 Arnhold J, Flemmig J. Human myeloperoxidase in innate and acquired immunity. Arch Biochem Biophys 2010; 500: 92-106
• 25 Lau D, Mollnau H, Eiserich JP, Freeman BA, Daiber A, Gehling UM, Brümer J, Rudolph V, Münzel T, Heitzer T, Meinrtz T, Baldus S. Myeloperoxidase mediates neutrophil activation by association with CD 11b/CD18 integrins. Proc Nat Acad Sci USA 2005; 102: 431-436
• 26 Haegens A, Heeringa P, Van Suylen RJ, Steele C, Aratani Y, OʼDonoghue RJJ, Mutsaers SE, Mossman BT, Wouters EFM, Vernooy JHJ. Myeloperoxidase deficiency attenuates lipopolysaccharide-induced acute lung inflammation and subsequent cytokine and chemokine production. J Immunol 2009; 182: 7990-7996
• 27 Faith M, Sukumaran A, Pulimood AB, Jacob M. How reliable an indicator of inflammation is myeloperoxidase activity?. Clin Chim Acta 2008; 396: 23-25
• 28 Ekmekci OB, Donma O, Sardoğan E, Yildirim N, Uysal O, Demirel H, Demir T. Iron, nitric oxide, and myeloperoxidase in asthmatic patients. Biochemistry (Moscow) 2004; 69: 462-467
• 29 Telles RW, Ferreira GA, Da Silva NP, Sato EI. Increased plasma myeloperoxidase levels in systemic lupus erythematosus. Rheumatol Int 2010; 30: 779-784
• 30 Kuno M, Seki N, Tsujimoto S, Nakanishi I, Kinoshita T, Nakamura K, Terasaka T, Nishio N, Sato A, Fujii T. Anti-inflammatory activity of non-nucleoside adenosine deaminase inhibitor FR234938. Eur J Pharmacol 2006; 534: 241-249
• 31 Haskó G, Pacher P, Deitch EA, Vizi ES. Shaping of monocyte and macrophage function by adenosine receptors. Pharmacol Ther 2007; 113: 264-275
• 32 Krenke R, Korczyński P. Use of pleural fluid levels of adenosine deaminase and interferon gamma in the diagnosis of tuberculous pleuritis. Curr Opin Pulm Med 2010; 16: 367-375
• 33 Sun CX, Young HW, Molina JG, Volmer JB, Schenermann J, Blackburn MR. A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. J Clin Invest 2005; 115: 35-43
• 34 Delano DL, Montesinos MC, Desai A, Wilder T, Fernandez P, Dʼeustachio P, Wiltshire T, Cronstein BN. Genetically-based resitance to the anti-inflammatory effects of methotrexate in the air pouch model of acute inflammation. Arthritis Rheum 2005; 52: 2567-2575
• 35 Nakamachi Y, Koshiba M, Nakazawa T, Hatachi S, Saura R, Kurosaka M, Kusaka H, Kumagai S. Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts. Arthritis Rheum 2003; 48: 668-674
• 36 Redington AE. Modulation of nitric oxide pathways: therapeutic potential in asthma and chronic obstructive pulmonary disease. Eur J Pharmacol 2006; 533: 263-276
• 37 Sakaguchi Y, Shirahase H, Kunishiro K, Ichikawa A, Kanda M, Uehara Y. Effect of combination of nitric oxide synthase and cyclooxygenase inhibitors on carrageenan-induced pleurisy in rats. Life Sci 2006; 79: 442-447
• 38 Chen H, Bai H, Xi M, Liu R, Qin X, Liang X, Zhang W, Zhang X, Li W, Hai C. Ethyl pyruvate protects rats from phosgene induced pulmonary edema by inhibiting cyclooxygenase2 and inducible nitric oxide synthase expression. J Appl Toxicol 2013; 33: 71-77
• 39 Park SJ, Lee YC. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir Res 2010; 11: 1-8
• 40 Wang Y, Liu Y. The IL-17 cytokine family and their role in allergic inflammation. Curr Opin Immunol 2008; 20: 697-702
• 41 Herbert C, Hettiaratchi A, Webb DC, Thomas PS, Foster PS, Kumar RK. Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma. Clin Exp Allergy 2008; 38: 847-856
• 42 Saraiva M, OʼGarra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10: 170-181
• 43 Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71-109
• 44 Nabe T, Ikedo A, Hosokawa F, Kishima M, Fujii M, Mizutani N, Yoshino S, Ishihara K, Akiba S, Chaplin DD. Regulatory role of antigen-induced interleukin-10, produced by CD4+ T cells, in airway neutrophilia in a murine model for asthma. Eur J Pharmacol 2012; 677: 154-162
• 45 Tsumbu CN, Deby-Dupont G, Tits M, Angenot L, Frederich M, Kohnen S, Mouithys-Mickalad A, Serteyn D, Franck T. Polyphenol content and modulatory activities of some tropical dietary plant extracts on the oxidant activities of neutrophils and myeloperoxidase. Int J Mol Sci 2012; 13: 628-650
• 46 Costa RS, Carneiro TCB, Cerqueira-Lima AT, Queiroz NV, Alcântara-Neves NM, Pontes-De-Carvalho LC, Velozo ES, Oliveira EJ, Figueiredo CA. Ocimum gratissimum Linn. and rosmarinic acid, attenuate eosinophilic airway inflammation in an experimental model of respiratory allergy to Blomia tropicalis . Int Immunopharmacol 2012; 13: 126-134
• 47 Johnson JJ. Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer Lett 2011; 305: 1-7
• 48 Saleh TS, Calixto JB, Medeiros YS. Anti-inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy. Br J Pharmacol 1996; 118: 811-819
• 49 Rao TS, Currie JL, Shaffer AF, Isakson PC. Comparative evaluation of arachidonic acid (AA)-and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation. Inflammation 1993; 17: 723-741
• 50 Giusti G, Galanti B. Adenosine deamisase: colorimetric method. In: Bergmeyer HU, editor Methods of enzymatic analysis. Weinheim: Verlag Chemie Press; 1984: 315-323
• 51 Green IC, Wagner DA, Glowski J, Skipper PL, Wishnok JS, Tannenbaum SB. Analysis of nitrate, nitrite and [¹⁵ N] nitrate in biological fluids. Anal Biochem 1982; 126: 131-138
• 52 Dalmarco EM, Astolfi G, Liz R, Córdova CMM, Fröde TS. Modulatory effect of mycophenolate mofetil on carrageenan-induced inflammation in the mouse air pouch model. Int Immunopharmacol 2012; 13: 476-482