Anti-inflammatory Activity of Bromelia hieronymi: Comparison with Bromelain

Abstract

Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action.

Key words

Bromelia hieronymi - Bromeliaceae - bromelain - anti-inflammatory - plant proteases

• References

• 1 Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Review. Cell Mol Life Sci 2001; 58: 1234-1245
• 2 Brien S, Lewith G, Walker A, Hicks SM, Middleton M. Bromelain as a treatment for osteoarthritis: a review of clinical studies. Evid Based Complement Alternat Med 2004; 1: 251-257
• 3 Pirotta F, de Giuli-Morghen C. Bromelain: anti-inflammatory and serum fibrinolytic activity after oral administration in the rat. Drugs Exp Clin Res 1978; 4: 1-20
• 4 Smyth RD, Brennan R, Martin GJ. Systemic biochemical changes following the oral administration of a proteolytic enzyme, bromelain. Arch Int Pharmacodyn 1962; 136: 230-236
• 5 Maurer H, Eckert K, Grabowska E, Eschmann K. Use of bromelain proteases for inhibiting blood coagulation. Patent WO PCT/EP 98/04406; 2000.
• 6 Livio M, Bertoni MP, De Gaetano G, Donati MB. Effects of bromelain on fibrinogen level, prothrombin complex and platelet aggregation in the rat – a preliminary report. Drugs Exp Clin Res 1978; 4: 49-53
• 7 Kumakura S, Yamashita M, Tsurufuji S. Effect of Bromelain on kaolin-induced inflammation in rats. Eur J Pharmacol 1988; 150: 295-301
• 8 Vellini M, Desideri D, Milanese A, Omini C, Daffonchio L, Hernandez A, Brunelli G. Possible involvement of eicosanoids in the pharmacological action of bromelain. Drug Res 1986; 36: 110-112
• 9 Gaspani L, Limiroli E, Ferrario P, Bianchi M. In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in the inflammatory exudate in rats. Pharmacology 2002; 65: 83-86
• 10 Bhui K, Tyagi S, Srivastava AK, Singh M, Roy PI, Singh R, Shukla Y. Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G2/M arrest to apoptosis. Mol Carcinogen 2011; 51: 231-243
• 11 Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol 2008; 128: 66-74
• 12 Hale LP, Haynes BF. Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation. J Immunol 1992; 149: 3809-3816
• 13 Mynott TL, Ladhams A, Scarmato P, Engwerda CR. Bromelain from pineapple stems proteolytically blocks activation of extracellular regulated kinase-2 in Tcells. J Immunol 1999; 163: 2568-2575
• 14 Hale LP, Greer PK, Sempowski GD. Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation. Clin Immunol 2002; 104: 183-190
• 15 Wen S, Huang THW, Li GQ, Yamahara J, Roufogalis BD, Li Y. Bromelain improves decrease in defecation in postoperative rats: modulation of colonic gene expression of inducible nitric oxide synthase. Life Sci 2006; 78: 995-1002
• 16 Hale LP, Greer PK, Trinh CT, Gottfried MR. Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease. Clin Immunol 2005; 116: 135-142
• 17 Netti C, Bandi GL, Pecile A. Antiinflammatory action of proteolytic enzymes administered orally compared with antiphlogistic compounds. Farmaco 1972; 27: 453-466
• 18 Uhlig G, Seifert I. Die Wirkung proteolytischer Enzyme auf das posttraumatische Syndrom. Fortschr Medizin 1981; 15: 554-556
• 19 Bruno MA. Aislamiento, purificación y caracterización de las proteasas de frutos Bromelia hieronymi Mez. (Bromeliaceae) [dissertation]. La Plata: National University of La Plata; 2007
• 20 Pardo MF. Endopeptidasas de Bromelia balansae Mez y su aplicación en la modificación de proteínas alimentarias [dissertation]. La Plata: National University of La Plata; 2004
• 21 Brullo A. Aislamiento y purificación de proteasas vegetales destinadas a la obtención de proteínas modificadas para uso alimentario [dissertation]. La Plata: National University of La Plata; 2003
• 22 Bruno MA, Pardo MF, Caffini NO, López LMI. Hieronymain I, a new cysteine peptidase isolated from unripe fruits of Bromelia hieronymi Mez (Bromeliaceae). J Protein Chem 2003; 22: 127-134
• 23 Bruno MA, Trejo SA, Avilés XF, Caffini NO, López LMI. Isolation and characterization of Hieronymain II, another peptidase isolated from fruits of Bromelia hieronymi Mez. Protein J 2006; 25: 224-231
• 24 Bruno MA, Trejo S, Caffini NO, López LMI. Purification and characterization of Hieronymain III. Comparison with other proteases previously isolated from Bromelia hieronymi Mez. Protein J 2008; 27: 426-433
• 25 Bruno MA, Lazza CM, Errasti ME, López LMI, Caffini NO, Pardo MF. Milk clotting and proteolytic activity of an enzyme preparation from Bromelia hieronymi fruits. Food Sci Technol 2010; 43: 695-701
• 26 Natalucci CL, Brullo A, López LMI, Hilal RM, Caffini NO. Macrodontin, a new protease isolated from fruits of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae). J Food Biochem 1995; 19: 443-454
• 27 Bradford MB. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
• 28 Winter CA, Risley EA, Nuss GW. Carrageenan-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 1962; 111: 544-547
• 29 Kalbhem D, Smalla H. Pharmacological studies on the antiphlogistic effect of pentosanpolysulfate in combination with metamizol. Arzneimittelforschung 1977; 27: 1050-1057
• 30 Meier R, Schuler W, Desaullis P. Zur Frage des Mechanismus der Hemmung des Bindegewebeswachstums durch Cortisone. Experientia 1950; 6: 468-471
• 31 Morris CJ. Carrageenan-induced paw edema in the rat and mouse. Methods Mol Biol 2003; 225: 115-121
• 32 Vinegar R, Schreiber W, Hugo R. Biphasic development of carrageenan edema in rats. J Pharmacol Exp Ther 1969; 166: 96-103
• 33 Di Rosa M, Giroud JP, Willoughby DA. Studies of mediators of the acute inflammatory response induced in rats in different sites by carrageenin and turpentine. J Pathol 1971; 104: 15-29
• 34 Di Rosa M, Sorrentino L. The mechanism of the inflammatory effect of carrageenin. Eur J Pharmacol 1968; 4: 340-343
• 35 Vinegar R, Macklin AW, Truax JF, Selph JL. Histopathological and pharmacological study of carrageenin inflammation in the rat. Pharmacologist 1971; 13: 284-290
• 36 Boughton-Smith NK, Deakin AM, Follenfan RL, Whittle BJR, Garland LG. Role of oxygen radicals and arachidonic acid metabolites in the reverse passive Arthus reaction and carrageenin paw oedema in the rat. Br J Pharmacol 1993; 110: 896-902
• 37 Di Rosa M, Willoughby DA. Screens for antiinflammatory drugs. J Pharm Pharmacol 1971; 23: 297-300
• 38 Siebert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson P. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA 1994; 91: 12013-12017
• 39 Nantel F, Denis D, Gordon R, Northey A, Cirino M, Metters KM, Chan CC. Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation. Br J Pharmacol 1999; 128: 853-859
• 40 Salvemini D, Wang Z-Q, Wyatt PS, Bourdon DM, Marino MH, Manning PT, Currie MG. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol 1996; 118: 829-838
• 41 Bailey PJ, Sturm A, Lopez-Ramos B. A biochemical study of the cotton pellet granuloma in the rat: Effects of dexamethasone and indomethacin. Biochem Pharmacol 1982; 31: 1213-1218
• 42 Ben Rhouma K, Sakly M. Involution of rat thymus: characterization of cytoplasmic glucocorticoid receptors, evidence of glucocorticoid resistant dexamethasone receptor-positive cells. Arch Int Physiol Biochim Biophys 1994; 102: 97-102
• 43 Hori Y, Hu D-E, Yasui K, Smither RL, Austin Gresham G, Fan T-PD. Differential effects of angiostatic steroids and dexamethasone on angiogenesis and cytokine levels in rat sponge implants. Br J Pharmacol 1996; 118: 1584-1591
• 44 Co DO, Hogan LH, Shin I-K, Sandor M. T-cell contributions to the different phases of granuloma formation. Immunol Lett 2004; 92: 135-142