Bromelain
Encyclopedia
Bromelain is a pineapple extract thought to be effective for reducing swelling (inflammation), especially of the nose and sinuses, after surgery or injury. It may also be used for a variety of other effects that remain scientifically unconfirmed and not authorized by regulatory authorities like the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

. These may include: hay fever, treating a bowel condition that includes swelling and ulcers ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

, removing dead and damaged tissue after a burn debridement
Debridement
Debridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...

, preventing the collection of water in the lung pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...

, relaxing muscles, stimulating muscle contractions, slowing clotting, improving the absorption of antibiotics, preventing cancer, shortening labor, and helping the body get rid of fat. Bromelain also contains chemicals that might interfere with the growth of tumor cells and slow blood clotting, according to laboratory research only.

"Bromelain" is also used as a culinary ingredient, primarily as a tenderizer. The term "bromelain" can refer to either of two protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s extracted from the plant family Bromeliaceae
Bromeliaceae
Bromeliaceae is a family of monocot flowering plants of around 3,170 species native mainly to the tropical Americas, with a few species found in the American subtropics and one in tropical west Africa, Pitcairnia feliciana...

, or it can refer to a combination of those enzymes along with other compounds produced in an extract.

Extract components

Bromelain extract is a mixture of protein-digesting enzymes—called proteolytic enzymes or proteases and several other substances in smaller quantities. The proteolytic enzymes are referred to as sulfhydryl proteases, since a free sulfhydryl group of a cysteine side-chain is required for function. The two main enzymes are:
  • Stem bromelain -
  • Fruit bromelain -


The other substances typically include peroxidase
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...

, acid phosphatase
Acid phosphatase
Acid phosphatase is a phosphatase, a type of enzyme, used to free attached phosphate groups from other molecules during digestion. It is basically a phosphomonoesterase...

, protease inhibitors, and calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

.

History

The first isolation of bromelain was recorded by the Venezuelan chemist Vicente Marcano (BU1 1.Phar. 5,77) in 1891 from the fruit of pineapple
Pineapple
Pineapple is the common name for a tropical plant and its edible fruit, which is actually a multiple fruit consisting of coalesced berries. It was given the name pineapple due to its resemblance to a pine cone. The pineapple is by far the most economically important plant in the Bromeliaceae...

. In 1892, Chittenden, assisted by Joslin and Meara, investigated the matter fully (Trans. Conn. Acad. Arts Sci. 8, 281-308), and called it 'bromelin'. Later, the term 'bromelain' was introduced and originally applied to any protease from any plant member of the plant family Bromeliaceae
Bromeliaceae
Bromeliaceae is a family of monocot flowering plants of around 3,170 species native mainly to the tropical Americas, with a few species found in the American subtropics and one in tropical west Africa, Pitcairnia feliciana...

.

Bromelain was first introduced as a therapeutic supplement in 1957. Research on bromelain was first conducted in Hawaii but more recently has been conducted in countries in Asia, Europe, and Latin America. Germany has recently taken a great interest in bromelain research; bromelain is currently the thirteenth-most-widely-used herbal medicine in Germany.

Source

Bromelain is present in all parts of the pineapple
Pineapple
Pineapple is the common name for a tropical plant and its edible fruit, which is actually a multiple fruit consisting of coalesced berries. It was given the name pineapple due to its resemblance to a pine cone. The pineapple is by far the most economically important plant in the Bromeliaceae...

 plant (Ananas sp.). However, the stem is the most common commercial source, presumably because it is readily available after the fruit has been harvested. Pineapples have had a long tradition as a medicinal plant among the natives of South and Central America.

Potential medical uses

Available in some countries as a product under the name 'Ananase', and commercially in the United States under the name 'NatuRelief', bromelain began its reputation for various uses in folk medicine
Folk medicine
-Description:Refers to healing practices and ideas of body physiology and health preservation known to a limited segment of the population in a culture, transmitted informally as general knowledge, and practiced or applied by anyone in the culture having prior experience.All cultures and societies...

. First introduced in medical research in 1957, bromelain may work by blocking some proinflammatory metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s when applied topically
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...

. Preliminary research indicates that bromelain may affect migration of neutrophils
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...

 to sites of acute inflammation. As a potential anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....

 agent, it may be useful for treating arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

, 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
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 or European Food Safety Authority
European Food Safety Authority
The European Food Safety Authority is an agency of the European Union that provides independent scientific advice and communication on existing and emerging risks associated with the food chain, created by European Regulation 178/2002....

. The Natural Medicines Comprehensive Database suggests that bromelain, when used in conjunction with trypsin
Trypsin
Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...

 and rutin
Rutin
Rutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is a citrus flavonoid glycoside found in buckwheat, the leaves and petioles of Rheum species, and asparagus...

 is as effective as some prescription analgesics in the management of osteoarthritis.

Systemic enzyme therapy (consisting of combinations of proteolytic enzymes such as bromelain, trypsin, chymotrypsin
Chymotrypsin
Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...

, and papain) has been investigated in Europe to evaluate the efficacy of proteolytic enzymes in the treatment of breast, colorectal, and plasmacytoma cancer patients. In mice with experimental colitis
Colitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...

, 6 months of dietary bromelain from pineapple stem or from fresh juice decreased the severity of colonic inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 and reduced the number of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

ous lesions in the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

.

As bromelain supplementation may affect heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....

, care should be used by those with heart disease.

Meat tenderizing

Along with papain
Papain
Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya .-Papain family:...

, bromelain is one of the most popular substances to use for meat tenderizing
Tenderizing
In cooking, tenderizing is a process to break down collagens in meat to make it more palatable for consumption.There are a number of ways to tenderize meat:*Mechanical tenderization, such as pounding or piercing....

.

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 will penetrate the meat and, by a process called forking, cause the meat to be tender and palatable when cooked. If the enzyme is allowed to work for too long, the meat may become too "mushy" for many consumers' preferences. Cooked or canned pineapple does not have a tenderizing effect, as the enzymes are heat-labile
Lability
Lability refers to something that is constantly undergoing change or something that is likely to undergo change.-Chemistry:The term is used to describe a relatively unstable and transient chemical species...

.

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 can be undesirable where it is inappropriate. In dishes that depend on their protein content for important attributes, uncooked pineapple or its juice can be a nuisance. For example, some dishes such as brawn
Head cheese
Head cheese , or brawn , is a cold cut that originated in Europe. A version pickled with vinegar is known as souse. Head cheese is not a cheese but a terrine or meat jelly made with flesh from the head of a calf or pig , and often set in aspic. Which parts of the head are used can vary, but the...

 and jelly
Gelatin
Gelatin is a translucent, colorless, brittle , flavorless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning in a similar...

 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 problem, the fruit should first be cooked, or at least parboiled sufficiently to inactivate the enzymes. In general, thorough heating to above about 65 degrees C will suffice. This problem does not affect dishes based on non-proteinaceaous gelling agents, such as agar, though such agents may be prevented from gelling by too much heating in acid recipes.

Bromelain prefers to cleave at Lys-
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

, Ala-
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...

, Tyr-
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

, Gly-
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

. Is activated by cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

, bisulfite
Bisulfite
Bisulfite ion is the ion HSO3−. Salts containing the HSO3− ion are termed bisulfites also known as sulfite lyes...

 salt, NaCN
Sodium cyanide
Sodium cyanide is an inorganic compound with the formula NaCN. This highly toxic colorless salt is used mainly in gold mining but has other niche applications...

, H2S
Hydrogen sulfide
Hydrogen sulfide is the chemical compound with the formula . It is a colorless, very poisonous, flammable gas with the characteristic foul odor of expired eggs perceptible at concentrations as low as 0.00047 parts per million...

, Na2S
Sodium sulfide
Sodium sulfide is the name used to refer to the chemical compound Na2S, but more commonly it refers to the hydrate Na2S·9H2O. Both are colorless water-soluble salts that give strongly alkaline solutions...

, and benzoate. It is inhibited by Hg++
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...

, Ag+
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...

, Cu++
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...

, a-1-antitrypsin, estatin A&B, Iodoacetate, TLCK, TPCK
Tosyl phenylalanyl chloromethyl ketone
Tosyl phenylalanyl chloromethyl ketone is a protease inhibitor. Its structural formula is 1-chloro-3-tosylamido-4-phenyl-2-butanone.-Uses:...

 

Pharmacodynamics

Bromelain, increases blood fibrinolytic activity as well as inhibiting fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...

 synthesis; bromelain also directly degrades fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....

 and fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...

. Kininogen and bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...

 serum and tissue levels are lowered by bromelain and it also effects prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....

 synthesis, which gives it's antiinflammatory effects. Bromelain has been found to reduce the excretion of proinflammatory cytokines as well as chemokines in a study into it's possible mechanism of action in ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

, inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...

, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

.

Production

It is produced in Thailand, Taiwan, and other tropical parts of the world where pineapples are grown.

Bromelain is prepared from the stem part of the pineapple plant after harvesting the fruit. This stem part is peeled, crushed, and pressed to get the juice containing the soluble bromelain enzyme. Further processing includes purification and concentration of the enzyme.

Other plant proteases

Other plant proteases include papain
Papain
Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya .-Papain family:...

 (from the papaya
Papaya
The papaya , papaw, or pawpaw is the fruit of the plant Carica papaya, the sole species in the genus Carica of the plant family Caricaceae...

), actinidin (from the kiwi fruit), and ficin (from the fig
Ficus
Ficus is a genus of about 850 species of woody trees, shrubs, vines, epiphytes, and hemiepiphyte in the family Moraceae. Collectively known as fig trees or figs, they are native throughout the tropics with a few species extending into the semi-warm temperate zone. The Common Fig Ficus is a genus of...

).

External links

  • The MEROPS
    Merops
    Merops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...

    online database for peptidases and their inhibitors: Stem Bromelain:C01.005, Fruit Bromelain:C01.028
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