Bromelain

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Bromelain
Pineapple1.JPG
Pineapple
one member of the Bromeliaceae family
Effective temperature 40–60°C
Optimal temperature 50–60°C
Deactivation temperature approximately above 65°C
Effective pH 4.0–8.0
Optimal pH 4.5–5.5

Bromelain is an extract derived from the stems of pineapples, although it exists in all parts of the fresh plant and fruit, which has many uses. The extract has a history of folk and modern medicinal use. As a supplement, it is thought to have anti-inflammatory effects. Bromelain also contains chemicals that might interfere with the growth of tumor cells and slow blood clotting, but no peer-reviewed research shows any efficacy against tumors. As a culinary ingredient, it is used primarily as a tenderizer.

The term "bromelain" may refer to either of two protease enzymes extracted from the plants of the family Bromeliaceae, or it may refer to a combination of those enzymes along with other compounds produced in an extract.

The US National Institute of Health rates bromelain as only possibly effective against osteoarthritis, but only when taken in combination with trypsin and rutin (Phlogenzym).[1] The same institute has stated it is possibly ineffective for preventing postexercise muscle tiredness. In addition, no evidence indicates efficacy of the product for any other disorder.[1]

Extract components[edit]

Stem bromelain
Identifiers
EC number 3.4.22.32
CAS number 37189-34-7
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Fruit bromelain
Identifiers
EC number 3.4.22.33
CAS number 9001-00-7
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

Bromelain extract is a mixture of protein-digesting (proteolytic) enzymes or proteases, and several other substances in smaller quantities. The proteolytic enzymes are sulfhydryl proteases, since a free sulfhydryl group of a cysteine side chain is required for function. The two main enzymes are:

The other substances typically include peroxidase, acid phosphatase, protease inhibitors, and calcium.

History[edit]

Pineapples have a long tradition as a medicinal plant among the natives of South and Central America. The first isolation of bromelain was recorded by the Venezuelan chemist Vicente Marcano[2] in 1891 from the fruit of pineapple. In 1892, Russell Henry Chittenden, assisted by Elliott P. Joslin and Frank Sherman Meara, investigated the matter fully,[3] and called it 'bromelin'. Later, the term 'bromelain' was introduced and originally the term was applied to any protease from any member of the plant family Bromeliaceae.

Bromelain was first introduced as a therapeutic supplement in 1957. First, research on bromelain was conducted in Hawaii, but more recently has been conducted in countries in Asia, Europe, and Latin America. Recently, researchers in Germany have taken a great interest in bromelain research. Currently, bromelain is the 13th-most widely used herbal medicine in Germany.[citation needed]

Sources[edit]

Bromelain is present in all parts of the pineapple plant (Ananas sp.),[citation needed] but the stem is the most common commercial source,[citation needed] presumably because large quantities are readily available after the fruit has been harvested.

Uses[edit]

Potential medical uses[edit]

Available in some countries as a product under the name 'Ananase', bromelain began its reputation for various uses in folk medicine and continues to be explored as a potential healing agent in alternative medicine. First introduced in medical research in 1957, bromelain may work by blocking some proinflammatory metabolites when applied topically. Bromelain may be used after surgery to reduce swelling.[citation needed] Preliminary research indicates bromelain may affect migration of neutrophils to sites of acute inflammation.[4]

As a potential anti-inflammatory agent, it may be useful for treating arthritis,[5] but has neither been confirmed in human studies for this use, nor is it approved with a health claim for such an effect by the Food and Drug Administration or European Food Safety Authority. The Natural Medicines Comprehensive Database suggests that bromelain, when used in conjunction with trypsin and rutin is as effective as some prescription analgesics in the management of osteoarthritis.[6]

Bromelain has not been scientifically proven to be effective in any diseases and it has not been licensed by the Food and Drug Administration for the treatment of any other disorder.

Systemic enzyme therapy (consisting of combinations of proteolytic enzymes such as bromelain, trypsin, chymotrypsin, and papain) has been investigated in Europe to evaluate the efficacy of proteolytic enzymes in the treatment of breast, colorectal, and plasmacytoma cancer patients.[7] In mice with experimental colitis, six months of dietary bromelain from pineapple stem or from fresh juice decreased the severity of colonic inflammation and reduced the number of cancerous lesions in the colon.[8]

Bromelain supplements, when taken with other medications (amoxicillin, antibiotics, anticoagulant/antiplatelet drugs), may increase the risk associated with heart rate, blood clotting, and bleeding after surgery.[6]

Controversy[edit]

While there have been studies which positively correlated the use of bromelain with reduction of symptom severity in osteoarthritis,[9][10] "[t]he majority of the studies have methodological issues that make it difficult to draw definite conclusions", as none definitively established efficacy, recommended dosage, long term safety, or adverse interaction with other medications.[11]

Meat tenderizing[edit]

Along with papain, bromelain is one of the most popular proteases to use for meat tenderizing. Today, about 90% of meat tenderizer is used in consumer households. Bromelain is sold in a powdered form, which is combined with a marinade, or directly sprinkled on the uncooked meat. The enzyme penetrates the meat, and by a process called forking, causes the meat to become tender and palatable when cooked. If the enzyme is allowed to work for too long, however, the meat may become too "mushy" for the preferences of many consumers.

Cooked or canned pineapple does not have a tenderizing effect, as the enzymes are heat-labile and destroyed in the cooking process. Some prepared meat products, such as meatballs and commercially available marinades, include pineapple and/or pineapple-derived ingredients.

Apart from the mushiness of meat that has been over-tenderized, the activity of bromelain and similarly proteolytic plant enzymes may be undesirable where it is inappropriate. In dishes that depend on their protein content for important attributes, uncooked pineapple or its juice may be a nuisance. For example, some dishes such as brawn and jelly rely on the setting of gelatin. They will not set if they contain raw pineapple or pineapple juice. Raw figs, papaya, and similarly proteolytic vegetable matter causes similar problems. To prevent the incompatibility with gelatin problem, the fresh fruit should be cooked, or at least parboiled, sufficiently to inactivate the enzymes before using in such dishes. In general, thorough heating to above about 65 °C will suffice.[12] This problem does not affect dishes based on nonproteinaceaous gelling agents, such as agar, although such agents may be prevented from gelling by too much heating in acid recipes.

Pharmacodynamics[edit]

Bromelain increases blood fibrinolytic activity, as well as inhibiting fibrinogen synthesis. It also directly degrades fibrin and fibrinogen. Kininogen and bradykinin serum and tissue levels are lowered by bromelain, and it also affects prostaglandin synthesis, which gives it its anti-inflammatory effects.[13] Bromelain has been found to reduce the excretion of proinflammatory cytokines, as well as chemokines in a study into its possible mechanism of action in ulcerative colitis, inflammatory bowel disease, and Crohn's disease.[14]

Production[edit]

Bromelain is produced in Thailand, Taiwan, and other tropical parts of the world where pineapples are grown. It is prepared from the stem of the pineapple plant after harvesting the fruit for other purposes. The stem is peeled, crushed, and pressed to obtain the juice containing the soluble bromelain enzyme. Further processing includes purification and concentration of the enzyme. In India, bromelain is manufactured by Excellent Biotechnologies, Bangalore, in large quantities.[citation needed]


Temperature stability[edit]

At the optimum temperature, the enzyme acts the fastest, but (at least the fruit variant) is destroyed within few minutes. After an hour at 50 °C (122 °F), 83% of the enzyme remains, while at 40 °C (104 °F), practically 100% remains.[15] As a result of this, the optimum temperature for maximum cumulated activity over time is 35-45 °C.[16] At room temperature, the enzyme can survive at least a week even under multiple freeze-thaw cycles.[17]

See also[edit]

References[edit]

  1. ^ a b National Institute of Health, US. "Medline Plus Supplements". 
  2. ^ "PDVSA article citing Vicente Marcano (in Spanish)".  (BU1 1.Phar. 5,77)
  3. ^ Chittenden, R H; Elliott P Joslin; Frank Sherman Meara (1892). "On the ferments contained in the juice of the pineapple (Ananassa sativa): together with some observations on the composition and proteolytic action of the juice". Transactions of the Connecticut Academy of Arts and Sciences 8: 281­–308. 
  4. ^ Fitzhugh DJ, Shan S, Dewhirst MW et al. (2008). "Bromelain treatment decreases neutrophil migration to sites of inflammation". Clin Immunol 128 (1): 66–74. doi:10.1016/j.clim.2008.02.015. PMC 2516972. PMID 18482869. 
  5. ^ Brien S, Lewith G, Walker A (2004). "Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies". Evidence-based complementary and alternative medicine: eCAM. 1 (3): 251–257. doi:10.1093/ecam/neh035. PMC 538506. PMID 15841258. 
  6. ^ a b "Bromelain". MedlinePlus. National Institute of Health. Retrieved 10 June 2011. 
  7. ^ Beuth J (2008). "Proteolytic enzyme therapy in evidence-based complementary oncology: fact of fiction?". Integr Cancer Ther 7 (4): 311–316. doi:10.1177/1534735408327251. PMID 19116226. 
  8. ^ Hale LP, Chichlowski M, Trinh CT, Greer PK (2010). "Dietary supplementation with fresh pineapple juice decreases inflammation and colonic neoplasia in IL-10-deficient mice with colitis". Inflamm Bowel Dis 16 (12): 2012–21. doi:10.1002/ibd.21320. PMC 2991605. PMID 20848493. 
  9. ^ Walker AF, Bundy R, Hicks SM, Middleton RW (2002). "Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults". Phytomedicine 9 (8): 681–6. PMID 12587686. 
  10. ^ Hale LP, Greer PK, Trinh CT, James CL (2005). "Proteinase activity and stability of natural bromelain preparations". Int Immunopharmacol 5 (4): 783–93. PMID 15710346. 
  11. ^ Brien S, Lewith G, Walker A, Hicks SM, Middleton D (2004). "Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies". Evid Based Complement Alternat Med 1 (3): 251–7. PMC 538506. PMID 15841258. 
  12. ^ Watt, J.M. & Breyer-Brandwijk, M.G., The Medicinal and Poisonous Plants of Southern and Eastern Africa, 2nd ed. Pub: E&S Livingstone 1962
  13. ^ Lotz-Winter H (June 1990). "On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects". Planta Med. 56 (3): 249–53. doi:10.1055/s-2006-960949. PMID 2203073. 
  14. ^ Onken JE, Greer PK, Calingaert B, Hale LP (March 2008). "Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro". Clin. Immunol. 126 (3): 345–52. doi:10.1016/j.clim.2007.11.002. PMC 2269703. PMID 18160345. 
  15. ^ http://kasetsartjournal.ku.ac.th/kuj_files/2010/A1010081847262467.pdf
  16. ^ http://www.biozym.de/datasheets/bromelain.php
  17. ^ Hale, Laura P.; Greer, Paula K.; Trinh, Chau T.; James, Cindy L. (2005). "Proteinase activity and stability of natural bromelain preparations". International Immunopharmacology 5 (4): 783–93. doi:10.1016/j.intimp.2004.12.007. PMID 15710346. 

External links[edit]