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Properties and Therapeutic Application of Bromelain: A Review

DOI: 10.1155/2012/976203

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Abstract:

Bromelain belongs to a group of protein digesting enzymes obtained commercially from the fruit or stem of pineapple. Fruit bromelain and stem bromelainare prepared differently and they contain different enzymatic composition. “Bromelain” refers usually to the “stem bromelain.” Bromelain is a mixture of different thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors. In vitro and in vivo studies demonstrate that bromelain exhibits various fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities. Bromelain is considerably absorbable in the body without losing its proteolytic activity and without producing any major side effects. Bromelain accounts for many therapeutic benefits like the treatment of angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics. It also relieves osteoarthritis, diarrhea, and various cardiovascular disorders. Bromelain also possesses some anticancerous activities and promotes apoptotic cell death. This paper reviews the important properties and therapeutic applications of bromelain, along with the possible mode of action. 1. Introduction Pineapple is the common name of Ananas comosus (syns. A. sativus, Ananassa sativa, Bromelia ananas, B. comosa). Pineapple is the leading edible member of the family Bromeliaceae, grown in several tropical and subtropical countries including Philippines, Thailand, Indonesia, Malaysia, Kenya, India, and China. It has been used as a medicinal plant in several native cultures [1] and these medicinal qualities of pineapple are attributed to bromelain (EC 3.4.22.32), which is a crude extract from pineapple that contains, among other compounds, various closely related proteinases, exhibiting various fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities in vitro and in vivo. Bromelain has been chemically known since 1875 and is used as a phytomedical compound [2]. Bromelain concentration is high in pineapple stem, thus necessitating its extraction because, unlike the pineapple fruit which is normally used as food, the stem is a waste byproduct and thus inexpensive [3]. A wide range of therapeutic benefits have been claimed for bromelain, such as reversible inhibition of platelet aggregation, sinusitis, surgical traumas [4], thrombophlebitis, pyelonephriti angina pectoris, bronchitis [5], and enhanced absorption of drugs, particularly of antibiotics [6, 7]. Several studies

References

[1]  S. Mondal, S. Bhattacharya, J. N. Pandey, and M. Biswas, “Evaluation of acute anti-inflametry effect of Ananas Comosus leaf extract in Rats,” Pharmocologyonline, vol. 3, pp. 1312–1315, 2011.
[2]  S. J. Taussig and S. Batkin, “Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application: an update,” Journal of Ethnopharmacology, vol. 22, no. 2, pp. 191–203, 1988.
[3]  R. M. Heinicke and W. A. Gortner, “Stem bromelain: a new protease preparation from pineapple plants,” Economic Botany, vol. 11, no. 3, pp. 225–234, 1957.
[4]  M. Livio, G. De. Gaetano, and M. B. Donati, “Effect of bromelain of fibrinogen level, protrombin complex and platelet aggregation in the rat-a preliminary report,” Drugs under Experimental and Clinical Research, vol. 1, pp. 49–53, 1978.
[5]  R. A. Neubauer, “A plant protease for potentiation of and possible replacement of antibiotics,” Experimental Medicine and Surgery, vol. 19, pp. 143–160, 1961.
[6]  G. Renzini and M. Varego, “Die resorsption von tetrazyklin ingenenwart von Bromelain bei oraler application,” Arzneimittel-Forschung Drug Research, vol. 2, pp. 410–412, 1972.
[7]  H. R. Maurer, “Bromelain: biochemistry, pharmacology and medical use,” Cellular and Molecular Life Sciences, vol. 58, no. 9, pp. 1234–1245, 2001.
[8]  B. N. Tochi, Z. Wang, S. Y. Xu, and W. Zhang, “Therapeutic application of pineapple protease (Bromelain): a review,” Pakistan Journal of Nutrition, vol. 7, no. 4, pp. 513–520, 2008.
[9]  S. J. Taussig, “The mechanism of the physiological action of bromelain,” Medical Hypotheses, vol. 6, no. 1, pp. 99–104, 1980.
[10]  L. P. Hale, “Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice,” International Immunopharmacology, vol. 4, no. 2, pp. 255–264, 2004.
[11]  C. M. Ley, A. Tsiami, Q. Ni, and N. Robinson, “A review of the use of bromelain in cardiovascular diseases,” Journal of Chinese Integrative Medicine, vol. 9, no. 7, pp. 702–710, 2011.
[12]  K. Chobotova, A. B. Vernallis, and F. A. A. Majid, “Bromelain's activity and potential as an anti-cancer agent: current evidence and perspectives,” Cancer Letters, vol. 290, no. 2, pp. 148–156, 2010.
[13]  J. V. Castell, G. Friedrich, C. S. Kuhn, and G. E. Poppe, “Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake,” American Journal of Physiology, vol. 273, no. 1, pp. G139–G146, 1997.
[14]  B. K. Bhattacharyya, “Bromelain: an overview,” Natural Product Radiance, vol. 7, no. 4, pp. 359–363, 2008.
[15]  A. D. Rowan and D. J. Buttle, “Pineapple cysteine endopeptidases,” Methods in Enzymology, vol. 244, pp. 555–568, 1994.
[16]  S. Yoshioka K Izutsa, Y. Asa, and Y. Takeda, “Inactivation kineticsof enzyme pharmaceuticals in aqueous solutions,” Pharmaceutical Research, vol. 4, pp. 480–485, 1991.
[17]  T. Harrach, K. Eckert, K. Schulze-Forster, R. Nuck, D. Grunow, and H. R. Maurer, “Isolation and partial characterization of basic proteinases from stem bromelain,” Journal of Protein Chemistry, vol. 14, no. 1, pp. 41–52, 1995.
[18]  A. D. Napper, S. P. Bennet, M. Borowski et al., “Purification and characterization of multiple forms of the pineapple-stem-derived cysteine proteinases ananain and comosain,” Biochemical Journal, vol. 301, no. 3, pp. 727–735, 1994.
[19]  W. Cooreman, “Bromelain,” in Pharmaceutical Enzymes- Properties and Assay Methods, R. Ruyssen and A. Lauwers, Eds., pp. 107–121, E. Story-Scientia Scientific Publishing Co., Gent, Belgium, 1978.
[20]  I. Y. Filippova, E. N. Lysogorskaya, E. S. Oksenoit, G. N. Rudenskaya, and V. M. Stepanov, “L-Pyroglutamyl-L-phenylalanyl-L-leucine-p-nitroanilide: a chromogenic substrate for thiol proteinase assay,” Analytical Biochemistry, vol. 143, no. 2, pp. 293–297, 1984.
[21]  J. Seifert, R. Ganser, and W. Brendel, “Absorption of a proteolytic enzyme originating from plants out of the gastro-intestinal tract into blood and lymph of rats,” Zeitschrift fur Gastroenterologie, vol. 17, no. 1, pp. 1–8, 1979.
[22]  P. S. Shiew, Y. L. Fang, and F. A. A. Majid, “In vitro study ofbromelain activity inartificial stomach juiceand blood,” in Proceedings of the 3rd International Conference on Biotechnology for the Wellness Industry, PWTC, 2010.
[23]  C. Neumayer, A. Fügl, J. Nanobashvili et al., “Combined enzymatic and antioxidative treatment reduces ischemia-reperfusion injury in rabbit skeletal muscle,” Journal of Surgical Research, vol. 133, no. 2, pp. 150–158, 2006.
[24]  World Health Organization, “Cardiovascular diseases,” 2011, http://www.who.int/cardiovascular diseases/en/.
[25]  R. M. Heinicke, L. van der Wal, and M. Yokoyama, “Effect of bromelain (Ananase) on human platelet aggregation,” Experientia, vol. 28, no. 10, pp. 844–845, 1972.
[26]  D. E. King, T. M. Ellis, C. J. Everett, and A. G. Mainous, “Medication use for diabetes, hypertension, and hypercholesterolemia from1988–1994 to 2001–2006,” Southern Medical Journal, vol. 102, no. 11, pp. 1127–1132, 2009.
[27]  E. R. Secor Jr., F. C. William, M. C. Michelle et al., “Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murin model of allergic disease,” in Cellular Immunology, vol. 237, pp. 68–75, 2005.
[28]  B. Juhasz, M. Thirunavukkarasu, R. Pant et al., “Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium,” American Journal of Physiology, vol. 294, no. 3, pp. H1365–H1370, 2008.
[29]  R. C. Lawrence, C. G. Helmich, F. Arnett, et al., “Estimates of prevalence of arthritis and selected musculoskeletal disorders in the United States,” Arthritis & Rheumatism, vol. 41, pp. 778–799, 1998.
[30]  N. M. Akhtar, R. Naseer, A. Z. Farooqi, W. Aziz, and M. Nazir, “Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee—a double-blind prospective randomized study,” Clinical Rheumatology, vol. 23, no. 5, pp. 410–415, 2004.
[31]  S. Brien, G. Lewith, A. Walker, S. M. Hicks, and D. Middleton, “Bromelain as a treatment for osteoarthritis: a review of clinical studies,” Evidence-Based Complementary and Alternative Medicine, vol. 1, no. 3, pp. 251–257, 2004.
[32]  C. F. Mojcik and E. M. Shevach, “Adhesion molecules: a rheumatologic perspective,” Arthritis and Rheumatism, vol. 40, no. 6, pp. 991–1004, 1997.
[33]  T. Bodi, “The effects of oral bromelains on tissue permeability to antibiotics and pain responseto bradykinin: double blind studies on human subjects,” Clinical Medicine, vol. 73, pp. 61–65, 1966.
[34]  S. Kumakura, M. Yamashita, and S. Tsurufuji, “Effect of bromelain on kaolin-induced inflammation in rats,” European Journal of Pharmacology, vol. 150, no. 3, pp. 295–301, 1988.
[35]  A. Cohen and J. Goldman, “Bromelain therapy in rheumatoid arthritis,” Pennsylvania Medical Journal, vol. 67, pp. 27–30, 1964.
[36]  H. Barth, A. Guseo, and R. Klein, “In vitro study on the immunological effect of bromelain and trypsin on mononuclear cells from humans,” European Journal of Medical Research, vol. 10, no. 8, pp. 325–331, 2005.
[37]  L. P. Hale and B. F. Haynes, “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,” Journal of Immunology, vol. 149, no. 12, pp. 3809–3816, 1992.
[38]  P. V. Lehmann, “Immunomodulation by proteolytic enzymes,” Nephrology Dialysis Transplantation, vol. 11, no. 6, pp. 953–955, 1996.
[39]  L. Desser, A. Rehberger, E. Kokron, and W. Paukovits, “Cytokine synthesis in human peripheral blood mononuclear cells after oral administration of polyenzyme preparations,” Oncology, vol. 50, no. 6, pp. 403–407, 1993.
[40]  L. Desser, A. Rehberger, and W. Paukovits, “Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro,” Cancer Biotherapy, vol. 9, no. 3, pp. 253–263, 1994.
[41]  K. Eckert, E. Grabowska, R. Stange, U. Schneider, K. Eschmann, and H. R. Maurer, “Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients,” Oncology Reports, vol. 6, no. 6, pp. 1191–1199, 1999.
[42]  C. R. Engwerda, D. Andrew, M. Murphy, and T. L. Mynott, “Bromelain activates murine macrophages and natural killer cells in vitro,” Cellular Immunology, vol. 210, no. 1, pp. 5–10, 2001.
[43]  C. R. Engwerda, D. Andrew, A. Ladhams, and T. L. Mynott, “Bromelain modulates T cell and B cell immune responses in vitro and in vivo,” Cellular Immunology, vol. 210, no. 1, pp. 66–75, 2001.
[44]  T. L. Mynott, A. Ladhams, P. Scarmato, and C. R. Engwerda, “Bromelain, from pineapple stems, proteolytically blocks activation of extracellular regulated kinase-2 in T cells,” Journal of Immunology, vol. 163, no. 5, pp. 2568–2575, 1999.
[45]  E. R. Secor Jr., A. Singh, L. A. Guernsey et al., “Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro,” International Immunopharmacology, vol. 9, no. 3, pp. 340–346, 2009.
[46]  J. Leipner, F. Iten, and R. Saller, “Therapy with proteolytic enzymes in rheumatic disorders,” BioDrugs, vol. 15, no. 12, pp. 779–789, 2002.
[47]  H. Lotz-Winter, “On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects,” Planta Medica, vol. 56, no. 3, pp. 249–253, 1990.
[48]  M. Livio, G. De Gaetano, and M. B. Donati, “Effect of bromelain on fibrinogen level, prothrombin complex factors and platelet aggregation in rat: a preliminary report,” Drugs under Experimental and Clinical Research, vol. 4, pp. 21–23, 1978.
[49]  M. De-Guili and F. Pirotta, “Bromelain: interaction with some protease inhibitors and rabbit specific antiserum,” Drugs under Experimental and Clinical Research, vol. 4, pp. 21–23, 1978.
[50]  S. J. Taussig and S. Batkin, “Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application: an update,” Journal of Ethnopharmacology, vol. 22, no. 2, pp. 191–203, 1988.
[51]  T. L. Mynott, S. Guandalini, F. Raimondi, and A. Fasano, “Bromelain prevents secretion caused by Vibrio cholerae and Escherichia coli enterotoxins in rabbit ileum in vitro,” Gastroenterology, vol. 113, no. 1, pp. 175–184, 1997.
[52]  D. S. Chandler and T. L. Mynott, “Bromelain protects piglets from diarrhoea caused by oral challenge with K88 positive enterotoxigenic Escherichia coli,” Gut, vol. 43, no. 2, pp. 196–202, 1998.
[53]  T. L. Mynott, R. K. J. Luke, and D. S. Chandler, “Oral administration of pro tease inhibits enterotoxigenic Escherichia coli receptor activity in piglet small intestine,” Gut, vol. 38, no. 1, pp. 28–32, 1996.
[54]  R. Béez, M. T. P. Lopes, C. E. Salas, and M. Hernández, “In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain,” Planta Medica, vol. 73, no. 13, pp. 1377–1383, 2007.
[55]  S. J. Taussig, J. Szekerczes, and S. Batkin, “Inhibition of tumour growth in vitro by bromelain, an extract of the pineapple plant (Ananas comosus),” Planta Medica, vol. 6, pp. 538–539, 1985.
[56]  B. B. Tysnes, H. R. Maurer, T. Porwol, B. Probst, R. Bjerkvig, and F. Hoover, “Bromelain reversibly inhibits invasive properties of glioma cells,” Neoplasia, vol. 3, no. 6, pp. 469–479, 2001.
[57]  A. Mantovani, P. Allavena, A. Sica, and F. Balkwill, “Cancer-related inflammation,” Nature, vol. 454, no. 7203, pp. 436–444, 2008.
[58]  R. L. Ferris and J. R. Grandis, “NF-κB gene signatures and p53 mutations in head and neck squamous cell carcinoma,” Clinical Cancer Research, vol. 13, no. 19, pp. 5663–5664, 2007.
[59]  S. P. Hussain and C. C. Harris, “Inflammation and cancer: an ancient link with novel potentials,” International Journal of Cancer, vol. 121, no. 11, pp. 2373–2380, 2007.
[60]  M. T. Wang, K. V. Honn, and D. Nie, “Cyclooxygenases, prostanoids, and tumor progression,” Cancer and Metastasis Reviews, vol. 26, no. 3-4, pp. 525–534, 2007.
[61]  K. Bhui, S. Prasad, J. George, and Y. Shukla, “Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway,” Cancer Letters, vol. 282, no. 2, pp. 167–176, 2009.
[62]  J. R. Huang, C. C. Wu, R. C. W. Hou, and K. C. Jeng, “Bromelain inhibits lipopolysaccharide-induced cytokine production in human THP-1 monocytes via the removal of CD14,” Immunological Investigations, vol. 37, no. 4, pp. 263–277, 2008.
[63]  R. C. W. Hou, Y. S. Chen, J. R. Huang, and K. C. G. Jeng, “Cross-linked bromelain inhibits lipopolysaccharide-induced cytokine production involving cellular signaling suppression in rats,” Journal of Agricultural and Food Chemistry, vol. 54, no. 6, pp. 2193–2198, 2006.
[64]  G. C. Tassman, J. N. Zafran, and G. M. Zayon, “Evaluation of a plate proteolytic enzyme for the control of inflammation and pain,” Journal of Dental Medicine, vol. 19, pp. 73–77, 1964.
[65]  G. C. Tassman, J. N. Zafran, and G. M. Zayon, “A double-blind crossover study of a plant proteolytic enzyme in oral surgery,” The Journal of Dental Medicine, vol. 20, pp. 51–54, 1965.
[66]  R. C. L. Howat and G. D. Lewis, “The effect of bromelain therapy on episiotomy wounds—a double blind controlled clinical trial,” Journal of Obstetrics and Gynaecology of the British Commonwealth, vol. 79, no. 10, pp. 951–953, 1972.
[67]  J. C. Houck, C. M. Chang, and G. Klein, “Isolation of an effective debriding agent from the stems of pineapple plants,” International Journal of Tissue Reactions, vol. 5, no. 2, pp. 125–134, 1983.
[68]  L. Rosenberg, Y. Krieher, E. Silverstain et al., Selectivity of a Bromelain Based Enzymatic Debridement Agent: A Porcine Study, Elsevier, 2012.
[69]  A. J. Singer, S. A. McClain, B. R. Taira, J. Rooney, N. Steinhauff, and L. Rosenberg, “Rapid and selective enzymatic debridement of porcine comb burns with bromelain-derived Debrase: acute-phase preservation of noninjured tissue and zone of stasis,” Journal of Burn Care and Research, vol. 31, no. 2, pp. 304–309, 2010.
[70]  S. Y. Wu, W. Hu, B. Zhang, S. Liu, J. M. Wang, and A. M. Wang, “Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds,” Journal of Surgical Research, vol. 176, pp. 503–509, 2012.
[71]  W. Hu, A. M. Wang, S. Y. Wu et al., “Debriding effect of bromelain on firearm wounds in pigs,” The Journal of Trauma, vol. 71, no. 4, pp. 966–972, 2011.
[72]  J. G. Miller, H. R. Carruthers, and D. A. R. Burd, “An algorithmic approach to the management of cutaneous burns,” Burns, vol. 18, no. 3, pp. 200–211, 1992.
[73]  R. L. Sheridan, R. G. Tompkins, and J. F. Burke, “Management of burn wounds with prompt excision and immediate closure,” Journal of Intensive Care Medicine, vol. 237, pp. 68–75, 1994.
[74]  R. E. Salisbury, “In-thermal burns,” in Plastic Surgery, J. C. McCarthy, Ed., vol. 1, pp. 787–830, 1990.
[75]  S. J. Taussig, M. M. Yokoyama, and A. Chinen, “Bromelain: a proteolytic enzyme and its clinical application: a review,” Hiroshima Journal of Medical Sciences, vol. 24, no. 2-3, pp. 185–193, 1975.
[76]  I. N. Moss, C. V. Frazier, and G. J. Martin, “Bromelain -the pharmacology of the enzyme,” Archives of International Pharmacody, vol. 145, pp. 166–189, 1963.

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