Table of Contents
Biotechnology Research International
Volume 2012, Article ID 976203, 6 pages
http://dx.doi.org/10.1155/2012/976203
Review Article

Properties and Therapeutic Application of Bromelain: A Review

Department of Biotechnology, Institute of Biomedical Education and Research, Mangalayatan University, Aligarh 202145, India

Received 25 September 2012; Accepted 13 November 2012

Academic Editor: Michael Hust

Copyright © 2012 Rajendra Pavan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked 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. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar
  7. H. R. Maurer, “Bromelain: biochemistry, pharmacology and medical use,” Cellular and Molecular Life Sciences, vol. 58, no. 9, pp. 1234–1245, 2001. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  9. S. J. Taussig, “The mechanism of the physiological action of bromelain,” Medical Hypotheses, vol. 6, no. 1, pp. 99–104, 1980. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  14. B. K. Bhattacharyya, “Bromelain: an overview,” Natural Product Radiance, vol. 7, no. 4, pp. 359–363, 2008. View at Google Scholar · View at Scopus
  15. A. D. Rowan and D. J. Buttle, “Pineapple cysteine endopeptidases,” Methods in Enzymology, vol. 244, pp. 555–568, 1994. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  32. C. F. Mojcik and E. M. Shevach, “Adhesion molecules: a rheumatologic perspective,” Arthritis and Rheumatism, vol. 40, no. 6, pp. 991–1004, 1997. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  35. A. Cohen and J. Goldman, “Bromelain therapy in rheumatoid arthritis,” Pennsylvania Medical Journal, vol. 67, pp. 27–30, 1964. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  38. P. V. Lehmann, “Immunomodulation by proteolytic enzymes,” Nephrology Dialysis Transplantation, vol. 11, no. 6, pp. 953–955, 1996. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Leipner, F. Iten, and R. Saller, “Therapy with proteolytic enzymes in rheumatic disorders,” BioDrugs, vol. 15, no. 12, pp. 779–789, 2002. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Mantovani, P. Allavena, A. Sica, and F. Balkwill, “Cancer-related inflammation,” Nature, vol. 454, no. 7203, pp. 436–444, 2008. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  74. R. E. Salisbury, “In-thermal burns,” in Plastic Surgery, J. C. McCarthy, Ed., vol. 1, pp. 787–830, 1990. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar