Advertisement

Systemic Enzyme Therapy: Fact or Fiction? A Review with Focus on Bromelains, Proteolytic Enzymes from the Pineapple Plant

  • Peter MeiserEmail author
  • Zhanjie Xu
  • Gilbert Kirsch
  • Claus Jacob
Chapter

Abstract

In this chapter, bromelain, a crude multi-component extract isolated from the stems of the pineapple plant, takes us on a tour through rather unusual therapeutic approaches and pharmacological mechanisms. Bromelain acts on several targets that address edematous, inflammatory, and immunological processes. Therefore, many indications have been treated with or are conceivable to be treated by use of this phytomedicine. Bromelain teaches us that we should keep an open mind toward at first sight exotic therapeutic approaches. A plea for the use of the potential of natural products that are well established in medical therapy for decades or even centuries.

Keywords

Anti-inflammatory Bromelain Cancer Therapeutic enzymes Myrosinase 

References

  1. Amini A, Ehteda A, Masoumi S, Moghaddam, Akhter J, Pillai K, Morris DL (2013) Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21). OncoTargets and therapy 6:403–409Google Scholar
  2. Baez R, Lopes MTP, Salas CE, Hernandez M (2007) In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain. Planta Med 73(13):1377–1383PubMedCrossRefGoogle Scholar
  3. Belanger-Quintana A, Burlina A, Harding CO, Muntau AC (2011) Up to date knowledge on different treatment strategies for phenylketonuria. Mol Genet Metab 104:S19–S25PubMedCrossRefGoogle Scholar
  4. Berg A, Peters M, Deibert P, Koenig D, Birnesser H (2005) Bromelain- Übersicht und Diskussion zur therapeutischen Anwendung und seiner Bedeutung in der Sportmedizin und Sporttraumatologie. Deutsche Zeitschrift für Sportmedizin 56(1):12–19Google Scholar
  5. Bhui K, Prasad S, George J, Shukla Y (2009) Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett 282(2):167–176PubMedCrossRefGoogle Scholar
  6. Bhui K, Tyagi S, Srivastava AK, Singh M, Roy P, Singh R, Shukla Y (2012) Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G2/M arrest to apoptosis. Mol Carcinogen 51(3):231–243CrossRefGoogle Scholar
  7. Borrelli F, Capasso R, Severino B, Fiorino F, Aviello G, De Rosa G, Mazzella M, Romano B, Capasso F, Fasolino I, Izzo AA (2011) Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice. Neurogastroent Motil 23(8):745–E331CrossRefGoogle Scholar
  8. Brakebusch M, Wintergerst U, Petropoulou T, Notheis G, Husfeld L, Belohradsky BH, Adam D (2001) Bromelain is an accelerator of phagocytosis, respiratory burst and killing of candida albicans by human granulocytes and monocytes. Eur J Med Res 6(5):193–200PubMedGoogle Scholar
  9. Brien S, Lewith G, Walker A, Hicks SM, Middleton D (2004) Bromelain as a treatment for osteoarthritis: a review of clinical studies. Evid-Based Compl Alt 1(3):251–257CrossRefGoogle Scholar
  10. Buttner L, Achilles N, Bohm M, Shah-Hosseini K, Mosges R (2013) Efficacy and tolerability of bromelain in patients with chronic rhinosinusitis—a pilot study. B-Ent 9(3):217–225PubMedGoogle Scholar
  11. Castell JV, Friedrich G, Kuhn CS, Poppe GE (1997) Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol-Gastr L 273(1):G139–G146Google Scholar
  12. Chobotova K, Vernallis AB, Majid FAA (2010) Bromelain’s activity and potential as an anti-cancer agent: current evidence and perspectives. Cancer Lett 290(2):148–156PubMedCrossRefGoogle Scholar
  13. Cohen A, Goldman J (1964) Bromelains therapy in rheumatoid arthritis. Pennsylvania Med J 67:27–30Google Scholar
  14. Desser L, Holomanova D, Zavadova E, Pavelka K, Mohr T, Herbacek I (2001) Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in human blood. Cancer Chemoth Pharm 47:S10–S15CrossRefGoogle Scholar
  15. Dhandayuthapani S, Perez HD, Paroulek A, Chinnakkannu P, Kandalam U, Jaffe M, Rathinavelu A (2012) Bromelain-induced apoptosis in GI-101A breast cancer cells. J Med Food 15(4):344–349PubMedCrossRefGoogle Scholar
  16. Eckert K, Grabowska E, Stange R, Schneider U, Eschmann K, Maurer HR (1999) Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients. Oncol Rep 6(6):1191–1199PubMedGoogle Scholar
  17. Enomoto T, Mineshita S, Shigei T (1968) Protective effect of stem bromelain against adrenaline pulmonary edema, and its dependence on the proteolytic activity. Jpn J Pharmacol 18(2):260–265PubMedCrossRefGoogle Scholar
  18. Fahey T, Stocks N, Thomas T (1998) Systematic review of the treatment of upper respiratory tract infection. Arch Dis Child 79(3):225–230PubMedCentralPubMedCrossRefGoogle Scholar
  19. FDA (2001) Partial list of enzyme preparations that are used in foods (GRAS). Center for Food Safety and Applied NutritionGoogle Scholar
  20. Fitzhugh DJ, Shan SQ, Dewhirst MW, Hate LP (2008) Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol 128(1):66–74PubMedCentralPubMedCrossRefGoogle Scholar
  21. Fokkens W, Lund V, Mullol J (2007) European position paper on rhinosinusitis and nasal polyps 2007. Rhinology 20 1–136Google Scholar
  22. Gaspani L, Limiroli E, Ferrario P, Bianchi M (2002) In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in the inflammatory exudate in rats. Pharmacology 65(2):83–86PubMedCrossRefGoogle Scholar
  23. Gilead L, Mumcuoglu KY, Ingber A (2012) The use of maggot debridement therapy in the treatment of chronic wounds in hospitalised and ambulatory patients. J Wound Care 21(2):78Google Scholar
  24. Guo R, Canter PH, Ernst E (2006) Herbal medicines for the treatment of rhinosinusitis: a systematic review. Otolaryng Head Neck 135(4):496–506CrossRefGoogle Scholar
  25. Hale LP, Greer PK, Sempowski GD (2002) Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation. Clin Immunol 104(2):183–190PubMedCrossRefGoogle Scholar
  26. Hale LP, Greer PK, Trinh CT, Gottfried AR (2005) Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease. Clin Immunol 116(2):135–142PubMedCrossRefGoogle Scholar
  27. Harrach T, Eckert K, Schulzeforster K, Nuck R, Grunow D, Maurer HR (1995) Isolation and partial characterization of basic proteinases from stem bromelain. J Protein Chem 14(1):41–52PubMedCrossRefGoogle Scholar
  28. Harrach T, Gebauer F, Eckert K, Kunze R, Maurer HR (1994) Bromelain Proteinases Modulate the Cd44 Expression on Human Molt-4/8 Leukemia and Sk-Mel-28 Melanoma-Cells in Vitro. Int J Oncol 5(3):485–488PubMedGoogle Scholar
  29. Heinicke R, Gortner W (1957) Stem bromelain, a new protease preparation from pineapple plants. Econ Bot 11:225–234CrossRefGoogle Scholar
  30. Huang JR, Wu CC, Hou RCW, Jeng KC (2008) Bromelain inhibits lipopolysaccharide-induced cytokine production in human THP-1 monocytes via the removal of CD14. Immunol Invest 37(4):263–277PubMedCrossRefGoogle Scholar
  31. Inchingolo F, Tatullo M, Marrelli M, Inchingolo AM, Picciariello V, Inchingolo AD, Dipalma G, Vermesan D, Cagiano R (2010) Clinical trial with bromelain in third molar exodontia. Eur Rev Med Pharmaco 14(9):771–774Google Scholar
  32. Johann K, Eschmann K, Meiser P (2011) Keine klinische Evidenz für ein erhöhtes Blutungsrisiko durch Bromelain bei perioperativem Einsatz. Sportverl Sportschad 25(2):108–113CrossRefGoogle Scholar
  33. Kalra N, Bhui K, Roy P, Srivastava S, George J, Prasad S, Shukla Y (2008) Regulation of p53, nuclear factor KB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. Toxicol Appl Pharm 226(1):30–37CrossRefGoogle Scholar
  34. Kolac C, Streichhan P, Lehr CM (1996) Oral bioavailability of proteolytic enzymes. Eur J Pharm Biopharm 42(4):222–232Google Scholar
  35. Kumakura S, Yamashita M, Tsurufuji S (1988) Effect of bromelain on kaolin-induced inflammation in rats. Eur J Pharmacol 150(3):295–301PubMedCrossRefGoogle Scholar
  36. Leggett JE (2004) Acute sinusitis: when-and when not-to prescribe antibiotics. Postgrad Med 115(1):13–19PubMedCrossRefGoogle Scholar
  37. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444PubMedCrossRefGoogle Scholar
  38. Maurer HR (2001) Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 58(9):1234–1245PubMedCrossRefGoogle Scholar
  39. Menon V, Harrington RA, Hochman JS, Cannon CP, Goodman SD, Wilcox RG, Schunemann HJ, Ohman EM (2004) Thrombolysis and adjunctive therapy in acute myocardial infarction. Chest 126(3):549s–575sPubMedCrossRefGoogle Scholar
  40. Miller JM, Opher AW (1964) Increased proteolytic activity of human blood serum after oral administration of bromelain. Exp Med Surg 22(4):277Google Scholar
  41. Moss JN, Frazier CV, Martin GJ (1963) Bromelains. The pharmacology of the enzymes. Arch Int Pharmacodyn Ther 145:166–189PubMedGoogle Scholar
  42. Muller S, Marz R, Schmolz M, Drewelow B, Eschmann K, Meiser P (2013) Placebo-controlled randomized clinical trial on the immunomodulating activities of low- and high-dose bromelain after oral administration new evidence on the antiinflammatory mode of action of bromelain. Phytother Res 27(2):199–204PubMedCrossRefGoogle Scholar
  43. Netti C, Bandi G, Pecile A (1966) Anti-inflammatory action of proteolytic enzymes of animal, vegetable or bacterial origin, administered orally compared with that of known antiphlogistic compounds. Il Farmaco Ed Pr 27(8):453–466Google Scholar
  44. Ogino M, Majima M, Kawamura M, Hatanaka K, Saito M (1996) Increased migration of neutrophils to granulocyte-colony stimulating factor in rat carrageenin-induced pleurisy: roles of complement, bradykinin, and inducible cyclooxygenase-2. Inflamm Res 45(7):335–346PubMedCrossRefGoogle Scholar
  45. Ohishi S, Uchida Y, Ueno A, Katori M (1979) Bromelain, a thiolprotease from pineapple stem, depletes high molecular-weight kininogen by activation of hageman-factor (factor-XII). Thromb Res 14(4–5):665–672CrossRefGoogle Scholar
  46. Pavan R, Jain S, Shraddha, Kumar A (2012) Properties and therapeutic application of bromelain: a review. Biotechnol Res Int 2012:976203Google Scholar
  47. Pillai K, Akhter J, Chua TC, Morris DL (2013) Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma. Cancer Invest 31(4):241–250PubMedCrossRefGoogle Scholar
  48. Reddy VB, Lerner EA (2010) Plant cysteine proteases that evoke itch activate protease-activated receptors. Brit J Dermatol 163(3):532–535CrossRefGoogle Scholar
  49. Secor ER, Carson WF, Cloutier MM, Guernsey LA, Schramm CM, Wu CA, Thrall RS (2005) Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease. Cell Immunol 237(1):68–75PubMedCentralPubMedCrossRefGoogle Scholar
  50. Secor ER, Carson WF, Singh A, Pensa M, Guernsey LA, Schramm CM, Thrall RS (2008) Oral bromelain attenuates inflammation in an ovalbumin-induced murine model of asthma. Evid-Based Compl Alt 5(1):61–69CrossRefGoogle Scholar
  51. Secor ER, Szczepanek SM, Singh A, Guernsey L, Natarajan P, Rezaul K, Han DK, Thrall RS, Silbart LK (2012) LC-MS/MS Identification of a bromelain peptide biomarker from Ananas comosus. pp 1–10 Merr. Evid-Based Compl Alt.\ Google Scholar
  52. Seifert J, Ganser R, Brendel W (1979) Absorption of a proteolytic-enzyme originating from plants out of the gastrointestinal-tract into blood and lymph of rats. Z Gastroenterol 17(1):1–8PubMedGoogle Scholar
  53. Shigei T, Sakuma A, Nishiwaki T (1967) A study on the protective effect of bromelain, crude pineapple proteases, against adrenaline-induced pulmonary edema in rats. Jpn Heart J 8(6):718–720PubMedCrossRefGoogle Scholar
  54. Smyth RD, Brennan R, Martin GJ (1962) Systemic biochemical changes following the oral administration of a proteolytic enzyme, bromelain. Arch Int Pharmacodyn Ther 136:230–236PubMedGoogle Scholar
  55. Taussig SJ, Batkin S (1988) Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 22(2):191–203PubMedCrossRefGoogle Scholar
  56. Taussig SJ, Yokoyama MM, Chinen A, Onari K, Yamakido M (1975) Bromelain: a proteolytic enzyme and its clinical application. A review. Hiroshima J Med Sci 24(2–3):185–193PubMedGoogle Scholar
  57. Uhlig G, Seifert J (1981) The effect of proteolytic enzymes (traumanase) on posttraumatic edema. Fortschr Med 99(15):554–556PubMedGoogle Scholar
  58. van Eimeren W (1994) Therapie traumatisch verursachter schwellungen. Thieme Verlag, Stuttgart, DeutschlandGoogle Scholar
  59. Vellini M, Desideri D, Milanese A, Omini C, Daffonchio L, Hernandez A, Brunelli G (1986) Possible involvement of eicosanoids in the pharmacological action of bromelain. Arzneimittel-Forsch 36(1):110–112 Google Scholar
  60. Yuan G, Wahlqvist ML, He G, Yang M, Li D (2006) Natural products and antiinflammatory activity. Asia Pacific J Clinical Nutr 15(2):143–152Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Peter Meiser
    • 1
    Email author
  • Zhanjie Xu
    • 1
    • 2
  • Gilbert Kirsch
    • 2
  • Claus Jacob
    • 3
  1. 1.URSAPHARM Arzneimittel GmbHSaarbrueckenGermany
  2. 2.Laboratoire d’Ingénierie Moléculaire et Biochimie PharmacologiqueUniversité de Lorraine 1MetzFrance
  3. 3.Bioorganische ChemieUniversitaet des SaarlandesSaarbrückenGermany

Personalised recommendations