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Therapeutic Application of Pineapple Protease (Bromelain): A Review



Bromelain (EC is a crude extract from the pineapple ( Ananas comosus ) plant that contains, among other components various closely related proteinases (stem bromelain, fruit bromelain, comosain and ananain) demonstrating both in vitro and in vivo several therapeutic properties including malignant cell growth, thrombus formation, inflammation, control of diarrhoea, dermatological and skin debridement among others. Bromelain also contains peroxidase, acid phosphatase, several protease inhibitors and organically bound calcium and remains stable over a wide range of pH 2 to 9. Available evidence indicates bromelain is well absorbed orally with its therapeutic effects being enhanced in a dose dependent manner. It has been demonstrated to be safe and an effective food supplement. However, all the mechanisms of its action remain unresolved.
Pakistan Journal of Nutrition 7 (4): 513-520, 2008
ISSN 1680-5194
© Asian Network for Scientific Information, 2008
Therapeutic Application of Pineapple Protease (Bromelain): A Review
Bitange Nipa Tochi , Zhang Wang , Shi - Ying Xu and Wenbin Zhang
1, 2 1 1 1
Department of Food Science and Engineering, School of Food Science and Technology,
Jiangnan University, Wuxi 214122, PR China
Pwani University College - Formerly Kilifi Institute of Agriculture, P.O. Box: 195, Kilifi, Kenya, East Africa
Abstract: Bromelain (EC is a crude extract from the pineapple (Ananas comosus) plant that
contains, among other components various closely related proteinases (stem bromelain, fruit bromelain,
comosain and ananain) demonstrating both in vitro and in vivo several therapeutic properties including
malignant cell growth, thrombus formation, inflammation, control of diarrhoea, dermatological and skin
debridement among others. Bromelain also contains peroxidase, acid phosphatase, several protease
inhibitors and organically bound calcium and remains stable over a wide range of pH 2 to 9. Available
evidence indicates bromelain is well absorbed orally with its therapeutic effects being enhanced in a dose
dependent manner. It has been demonstrated to be safe and an effective food supplement. However, all the
mechanisms of its action remain unresolved.
Key words: Bromelain, pineapple, proteinases, inflammation
Pineapple (Ananas comosus) native to Central and
South America, is grown in several tropical and sub-
tropical countries including Hawaii, India, China, Kenya,
South Africa, Malaysia, the Philippines and Thailand.
It has been used as a medicinal plant in several native
cultures and bromelain has been chemically known
since 1876 (Peckoldt et al., In: Taussig, 1988).
Bromelain obtained from the stems of the pineapple
plant contains all the soluble components of the
pineapple stem in their original properties, which may
involve malignant cell growth, thrombus formation,
inflammation, control of diarrhoea, dermatological and
skin debridement (Cohen, 1964; Taussig and Batkin,
1988; Kelly, 1996; Maurer, 2001).
Heinecke and Gortner (1957) found that bromelain
concentrations is high in pineapple stems necessitating
its extraction and use as a phytomedical compound
because unlike the pineapple fruit which is normally
used as food, the stems are a waste by-product and
thus inexpensive.
The main proteolytic constituents contained in
pharmacological preparations or food supplements of
bromelain (stem bromelain, fruit bromelain and
ananain) are also present in the pineapple fruit (Hale et
al., 2005). Bromelain’s primary component is a
Sulfhydryl proteolytic fraction. Bromelain also contains a
Peroxidase, acid Phosphatase, several protease
inhibitors and organically bound calcium (Kelly, 1996).
Bromelain activity is stable over a wide pH range
(Cohen, 1964; Taussig and Batkin, 1988; Kelly, 1996;
Maurer, 2001; Heinecke and Gortner, 1957; Hale et al.,
2005; Mynott et al., 1999; Cooreman et al., 1976).
Therefore it may not be necessary to enteric-protect the
protease from acid conditions in the stomach. However,
it may be necessary to protect the enzyme from digestion
by acid proteases in the gut. It may be administered with
a buffering agent, for example bicarbonate or in water or
in a solution containing nutrients to assist with
absorption of fluid and nutrients (Mynott et al., 1999).
Several studies have been carried out and results
generated indicate bromelain has useful phytomedical
applications. However, these results are yet to be
amalgamated and critically compared so as to chat the
way forward as to whether bromelain will gain wide
acceptance as a phytomedical supplement. The
purpose of the present paper is to highlight some
relevant contributions regarding bromelain’s
phytomedical applications that have been reported in
recent times.
Anti - inflammatory agent: Botanicals such as Ananas
comosus (Pineapple) and their extracts (bromelain) have
been used clinically as anti-inflammatory agents in
rheumatoid arthritis, soft tissue injuries, colonic
inflammation, chronic pain and asthma (Taussig and
Batkin, 1988; Kelly, 1996; Maurer, 2001; Cooreman et al.,
1976; Izaka et al., 1972; Hale et al., 2005; Jaber, 2002)
and are currently in use as anti-inflammatory agents
(Ammon, 2002; Lemay et al., 2004; Darshan and
Doreswamy, 2004).
The major mechanism of action of bromelain appears to
be proteolytic in nature, although evidence also
suggests an immunomodulatory and hormone like
activity acting via intracellular signalling pathways. In
vitro studies have shown that bromelain can inhibit pre-
incubated with medium alone (PMA) - induced T cell
production of the Th cytokine IL - 4 and to a lesser
degree the Th cytokines IL-2 and induced interferon-
gamma (IFN-() via modulation of the extracellular
Tochi et al.: Bromelain’s Pharmacology
regulated kinase-2 (ERK-2) intracellular signallingprotection techniques. These results could explain
pathway (Mynott et al., 1999). Bromelain has also beenearlier reports that bromelain decreased intestinal
shown to reduce cell surface receptors such asinflammation in human with UC (Kane and Goldberg,
hyaluronan receptor CD44, which is associated with2000).
leukocyte migration and induction of proinflammatoryWalker et al. (2002), in their pilot study while
mediators (Engwerda et al., 2001; Eckert et al., 1999;investigating the effect of bromelain on acute knee pain,
Hale et al., 2002). Manhart et al. (2002) have shownreported significant improvement after a month’s
bromelain to significantly reduce CD4 T lymphocytes,intervention. These results were consistent with earlier
which are primary effectors in animal models ofreports of bromelain supplementation (Uhlig, 1981;
inflammation. Vogler, 1988; Lotti et al., 1993) even though they could
Beneficial effects of bromelain have been suggested ornot be compared directly. Meanwhile Akhtar et al. (2004)
proven in a variety of inflammatory disease and animalin their study where they assessed the efficacy of an oral
models of inflammation. These include immunologicallyenzyme combination (ERC: Enzyme-rutin combination
mediated arteriosclerosis in rat aortic allograftswhich contains rutin and enzymes bromelain and
(Gaciong et al., 1996), the experimental allergictrypsin) versus diclofenac (a non-steroidal anti-
encephalomyelitis (EAE) model for the humaninflammatory drug-NSAID) among patients with knee
autoimmune disease multiple sclerosis (Targoni et al.,osteoarthritis (OA) in a double blind randomized version,
1999; Hale et al., 2005), IgE- mediated perennial allergic found ERC to be as equally efficacious to diclofenac.
rhinitis (Thornhill and Kelly, 2000) and collagen-inducedThese results are consistent with those reported earlier
arthritis in the rat (Rovenska et al., 2001). In their studyby (Vogler, 1988; Klein and Kullich, 2000; Tilwe et al.,
on bromelain’s anti-inflammatory effects in an2001). More so, unlike diclofenac, which exhibits
ovalbumin - induced murine model of allergic airwayinherent toxicities, ERC has a well known superior safety
disease (AAD), Secor et al. (2005) observed thatand tolerable profile (Akhtar et al., 2004).
bromelain demonstrated both anti-inflammatory and
immunomodulatory effects. In this particular study, theyBromelain as an anti-tumour agent: Pharmacological
found that bromelain treatment significantly reduced theagents with modulation of anti-inflammatory, proteolytic,
primary outcomes of murine AAD: Total bronchoalveolar platelet aggregation inhibition and prostaglandin
lavage (BAL) leukocytes (eosinophilis and lymphocytes), synthesis have been considered to be beneficial in
IL-13, CD4 T cells, CD8 T cells and CD4 CD25 T regulating tumour growth and its metastasis (Batkin et
+ + + +
cells, while also altering the CD4 /CD8 ratio. Theseal., 1985; Honn, 1983; Sato et al., 1983). Bromelain, with
+ +
findings indicate that systemic bromelain treatmentsimilar regulating actions, has shown protective
reduces an allergen induced localized airwayproperties on tumour cell growth retardation and lung
inflammatory process. metastasis (Batkin et al., 1985; Batkin et al., 1988a;
Kane and Goldberg (2000) gave a description of twoBatkin et al., 1988b; Taussig and Batkin, 1988).
patients suffering from ulcerative colitis (UC) that wasBatkin et al. (1988b) while studying the antimetastatic
refractory to conventional treatment, who rapidly entered effect of bromelain with or without its proteolytic and
and remained in clinical and endoscopic remission afteranticoagulant activities in the animal model of Lewis
self treatment with oral bromelain obtained from alung carcinoma, reported significant reduction in total
healthy food store. Studies by Hale (2004) show thatnumber of metastasis in both active and inactive
daily treatment with 5mg of oral bromelain significantlybromelain as compared to control groups. This
decreased spontaneous colon inflammation in IL-10 phenomenon had been reported earlier by Batkin et al.
mice. They further did show that anti-inflammatory activity (1985) whose study of three cell lines was done in vitro.
of bromelain is dependent on its proteolytic activity. In both studies, they conclude that bromelain could be
Wen et al. (2006) while studying the effect of bromelainhaving other pharmacological entities besides its
on postoperative defecation in rats, supports Hale’srecognized proteolytic anticoagulant functions.
(2004) findings that proteolytic activity of bromelain in the Recently, study results reported by researchers at the
colonic micro-environment is not only responsible for itsQueensland Institute of Medical Research-QIMR (QIMR,
anti-inflammatory activity but may be involved in the2005), give a window of hope for this phenomenon.
improvement of post operative ileus. That orallyWhile studying bromelain, researchers at QIMR reported
administered bromelain retains its proteolytic activity,the discovery of two proteins they named CCS and CCZ
was previously documented only in the small intestine and found that they could block growth of a broad range
of pigs (Mynott et al., 1996; Chandler and Mynott, 1998). of tumour cells including breast, lung, colon, ovarian and
The bromelain used in this study was enterically melanoma. However, the study is on going and these
protected. In his studies however, Hale (2004)results are not reliable at the moment. Batkin et al. (1985
showed that oral bromelain retains its proteolytic activityand 1988a) noted that in vitro Lewis lung cancer cell
throughout the entire gastrointestinal tract of mice in thegrowth retardation was a necessary correlate to
absence of encapsulation or other classic entericantimetastatic activity. In this regard therefore,
Tochi et al.: Bromelain’s Pharmacology
peroxidase and proteolytic anticoagulant activities maycapable of inhibiting both platelet aggregation in vitro
not be relevant features of bromelain’s antimetastaticand in vivo, as well as platelet-stimulated invasiveness
potential. of tumour cells. Thus what was described and used as
Maurer et al. (1988) found that bromelain may inducefolk medicine by the natives of the tropics over a Century
differentiation of leukemic cells in vitro and proposedago as over time been confirmed to have
this phenomenon as a possible mechanism of action.pharmaceutical applications. However, more research
In their studies, Grabowska et al. (1997) found thatis required to determine the structure and characteristics
B16F10 mouse melanoma cells, pre-incubated in vitroof the two compounds (CCS and CCZ) that were
with bromelain, significantly reduced lung metastaticreported by researchers at the QIMR (QIMR, 2005).
tumour weight to about three times. However, no survival
benefit was seen. Furthermore bromelain diminishedBromelain promotes debridement of burns: Burns are
the capacity of these cells to migrate through ancharacterized by formation of an eschar, which is made
extracellular matrix layer in an in vitro invasion assay and up of burned and traumatized tissue. The eschar not
inhibited the growth of tumour cells in a concentrationonly hinders accurate diagnosis of the burn’s depth but
dependent manner, whereas the anti-proliferation effectalso serves as a medium for bacterial growth and
did not correlate with the proteolytic activity. Earliertherefore a source of infection, contamination and
studies by Goldstein et al. (1975) and Taussig andsepsis of the injury and to the neighbouring originally
Goldstein (1976) reported that bromelain feedingundamaged tissues (Rosenberg et al., 2004). Rapid
enhanced the resistance of mice to the harmful effect ofdebridement considerably reduces morbidity and
UV (Ultra Violet) irradiation. It took twice as long for themortality of severely burned patients. It permits early skin
bromelain fed group to develop pre-cancerous lesionsgrafting and lessens the problems of infection,
as compared to the control group. Finally, humancontamination and sepsis thus abbreviating the
platelets pre-treated in vitro with bromelain lost theirconvalescence period (Maurer, 2001; Sheridan et al.,
capacity to stimulate the invasiveness of several1994; Sheridan et al., 1998; Prasanna et al., 1994;
metastatic tumour cells in the in vitro invasion assay.Monafo, 1974; Nada et al., 1998).
Meanwhile it has been shown that metastasized cells,While surgical debridement is non-selective, chemical
while migrating through the vessels, carry CD44debridement removes only the burned denatured skin
adhesion molecules on their surface by which they(Maurer, 2001; Sheridan et al., 1994; Janzekovic, 1970;
adhere to endothelial cells via the ligand hyaluron.Salisbury, 1990; Miller et al., 1992). Furthermore,
Bromelain preferentially cleaves off CD44 molecules bysurgical excision is painful and exposes patients to the
virtue of its proteolytic activity, thus inhibiting the firstrisks of repeated anaesthesia and significant bleeding.
steps of the metastatic process (Eckert et al., 1999; Hale Enzymatic debridement has been suggested with
et al., 2002; Hale and Haynes, 1992). experimental runs giving positive results. Topical
Maurer (2001) noted that metastasized tumour cellsbromelain (35% in a lipid base) was reported to achieve
carry the receptor (uPAR) for urokinase plasminogencomplete debridement on experimental burns in rats in
activator (uPA), which generates plasmin fromabout 2 days, as compared with collagenase, which
plasminogen. Plasmin degrades the extracellular matrixrequired about 10 days, with no side effects or damage
(ECM), composed of collagen type IV, laminin andto adjacent burned tissue (Klaue et al., 1979). When
fibronectin. Tumour cells also secrete matrixtopical bromelain was used for frostbite eschar removal,
metalloproteinases (MMPs), enabling the malignantno debridement other than of superficial eschar layers
cells to invade through the ECM. Bromelain diminisheswas noted; after two topical applications of bromelain,
uPAR expression and uPA activity, thus inhibiting thefrostbite injuries remained unaffected (Ahle and Hamlet,
invasion step of metastasis. Maurer further notes that1987).
interactions between tumour cells and platelets takeRosenberg et al. (2004), reported complete debridement
place on different levels i.e. intravasal distribution,of the eschar after only one to two brief applications with
adhesion on endothelial cells, invasion andminimal side effects and no blood loss. In the same
extravasation. Platelets he notes, directly bind to tumour study, no specific debridase (a bromelain derived
cells, a process promoted by the release of factors such debriding agent) related morbidity or mortality was
as platelet factor 4, thrombospondin, thrombin andnoted. However, due to incomplete data in a large
gelatinase A from platelets, which facilitate thrombusnumber of subjects, inaccuracies may have been
formation. Apart from this, transforming growth factor- $possible thus calling for more controlled studies to
(TGF-$), produced by both platelets and tumour cells,assess the safety and efficacy of a proteolytic enzyme for
plays an important role: it induces the synthesis of ECMenzymatic skin debridement.
proteins and stimulates the activity of uPA, MMPs and
angiogenesis. Thus, disturbance of the bloodEffects of bromelain on diarrhoea: Diarrhoea is a major
coagulation system may lead to the formation of thrombi cause of illness and death in children and young
by aggregating platelets and tumour cells. Bromelain isanimals (Cravioto et al., 1988; Smith and Lingood, 1982;
Tochi et al.: Bromelain’s Pharmacology
Roselli et al., 2007). Vibro cholerae and enterotoxigenicBromelain improves decrease in defecation in ileus
Escherichia coli (ETEC) are two important
microorganisms that cause diarrhoea Levine et al.
(1983). ETEC produces one or both of a heat-labile
(LT) and/or heat stable enterotoxin (either STa or STb)
and V.cholerae liberate cholera toxin (CT) (Mynott et al.,
1997). To contain this problem, drugs such as
chlorpromazine, nicotinic acid, loperamide and
berberine sulfate have been used in animal models to
inhibit secretion by CT and LT (Guandalini et al., 1984;
Holmgren et al., 1978; Turjman et al., 1978). Berberine,
chlorpromazine and indomethacin also reduce secretion
induced by STa (Greenberg et al., 1980; Abbey and
Knoop, 1979; Guandalini et al., 1987). Despite the
efficacy of these antisecretory compounds in animals,
none are routinely available for use in children and
adults because of adverse side effects or the large
doses required for efficacy (Chandler and Mynott, 1998).
Over time, oral rehydration therapy which has a
significant impact on morbidity and mortality of patients
with acute infectious diarrhoea has been used.
However, oral rehydration therapy does not interfere with
the secretory process nor diminish diarrhoea (Field,
1981). Bromelain has been demonstrated to have anti-
diarrhoea activity (Chandler and Mynott, 1998; Thomson
et al., 2001).
Studies by Mynott et al. (1997) have reported stem
bromelain to show antisecretory properties. Using a
rabbit ileum mounted in using chambers, they showed
that bromelain could prevent net changes in short-circuit
current (Isc) and therefore, fluid secretion mediated by
secretagogues that act through cAMP (cyclic-3, 5-
adenosine monophosphate), cGMP (cyclic-3, 5-
guanosine monophosphate) and calcium-dependent
signalling pathways. Because most toxins that cause
diarrhoea activate one of these pathways, bromelain
would be expected to be an effective anti diarrhoea
nutraceutical drug.
The efficacy of bromelain in this study was 62% in
preventing LT induced secretion, 51% effective against
CT and 35% effective against STa. Bromelain alsogene expression is involved in the improvement by
prevented secretory changes caused by prostaglandin
E, theophylline, calcium-ionophore A23187, 8-Br-cAMP
(8-bromocyclic-3, 5-adenosine monophosphate) and 8-
Br-cGMP (8- bromocyclic-3, 5-guanosine mono-
phosphate), well known intracellular mediators of ion
secretion. The efficacy of bromelain was reported not
caused by reduced tissue viability resulting from its
proteolytic effects on enterocytes, indicated by
experiments measuring uptake of nutrients into
intestinal cells and experiments measuring short circuit
responses to glucose. Meanwhile studies by Roselli et
al. (2007) on the effect of different plant extracts and
natural substances (PENS) against membrane damage
induced by ETEC in pig intestinal cells showed
bromelain to be among those with protective effect.
condition: Postoperative gastrointestinal dysmotility
(ileus) is a common consequence of abdominal surgery
causing significant patient discomfort (nausea, vomiting,
abdominal distension and inability to eat or defecate),
and often leads to more serious problems (acute gastric
dilatation, aspiration, respiratory compromise, cardiac
arrhythmia and perforation). Due to limited therapy
specific for this procedure, ileus remains an important
clinical problem (Wen et al., 2006).
In the US, bromelain is sold in health food stores as a
nutritional supplement to promote digestive health and
as an anti-inflammatory medication for horses (Hale,
2004). It has been used successfully as a digestive
enzyme following pancreatectomy in cases of exocrine
pancreas insufficiency and in other intestinal disorders
(Knill-Jones et al., 1970). Recently, it was reported that
stool discharge improved in some Japanese patients
concomitantly suffering from haemorrhoids and
constipation after using bromelain {private
communication in (Wen et al., 2006). This in essence
suggests that bromelain may improve intestinal
propulsive motility.
In another study, the combination of ox bile, pancreatin
and bromelain was shown to be effective in lowering
stool fat excretion in patients with pancreatic
steatorrhoea. In addition, this combination resulted in a
gain in weight in most cases as well as enhanced
subjective feeling of well being. Symptomatic
improvement was also noted in relation to pain,
flatulence and stool frequency (Balakrishnan et al.,
1981). In a recent study, Wen et al. (2006) did show that
treatment with 500 mg/kg bromelain significantly
increased wet weight and water content of faecal pellets
to near normal levels in postoperative rats. The results
suggest that bromelain may play an important role in
treatment of ileus. In the same study, bromelain
treatment was shown to significantly suppress
overexpression of colonic iNOS mRNA, accompanied by
improvement of decrease in defecation in postoperative
rats. It is therefore suggested that modulation of iNOS
bromelain of the decreased defecation in postoperative
rats, at least in part, by inhibiting colonic iNOS gene
expression probably through NF- B pathway.
Bromelain inhibits thrombus formation: Studies have
indicated that bromelain prevents aggregation of human
blood platelets in vivo and in vitro, prevents or minimizes
the severity of angina pectoris and transient ischemic
attacks (TIA), is useful in the prevention and treatment of
thrombosis and thrombophlebitis, may break down
cholesterol plaques and exerts a potent fibrinolytic
activity (Taussig and Nieper, 1979; Kelly, 1996).
Furthermore, it has been suggested that bromelain
increases vessels wall permeability to oxygen and
nutrients while increasingly thinning blood both of which
aid in these conditions (Kelly, 1996).
Tochi et al.: Bromelain’s Pharmacology
Heinicke et al. (1972) were the first to report thatonset of these diseases (Wiest-Ladenburger et al.,
bromelain prevents aggregation of blood platelets. In1997; Emancipator et al., 1997; White et al., 1991). Later,
their study carried among human volunteers with aHale (2004) unexpectedly found bromelain to exhibit
history of heart attack or stroke or with people havingstrong immunogenicity following oral dosing. In further
high aggregation values, as well as with health subjects, studies following this phenomenon, Hale et al. (2006)
oral administration of bromelain (160-1000 mg per day)reported that repeated exposure was necessary for
decreased aggregation of blood platelets in all thedevelopment of anti-bromelain antibodies, with
subjects. Later studies by Nieper (1978), whoexposure period ranging from 3 to 6 weeks on a dose
administered 400-1000 mg per day of bromelain to 14dependent manner.
patients with angina pectoris resulted in the
disappearance of symptoms in all patients within 4 to 90
days but reappeared after bromelain administration was
Metzig et al. (1999) showed that pre-incubation of human
platelets with 10ug/ml bromelain completely prevents
thrombin induced platelet aggregation in vitro and also
reduced the adhesion of thrombin stimulated,
fluorescently labelled platelets to bovine aorta
endothelial cells. Similarly, they reported that oral (60
mg/kg) and intravenous (30 mg/kg) bromelain inhibited
in vivo thrombus formation in a model of laser-induced
thrombosis in rats. The ability of bromelain to
influence these conditions could be due to its ability to
breakdown fibrinous plaques. Bromelain has been
shown to dissolve arteriosclerotic plaque in rabbit aorta
in vivo and in vitro (Taussig and Nieper, 1979). Later,
Hale et al. (2002) showed that in vitro bromelain
treatment of leukocytes in whole blood proteolytically
altered 14 of 59 leukocyte makers studied. It is important
to note that bromelain induced loss of CD41 and
CD42a via proteolysis would be expected to decrease
platelet function and thus inhibit thrombus formation.
Bromelain gives strong immunogenicity: Bromelain
has been shown to remove T-cell CD44 molecules from
lymphocytes among other bromelain sensitive
molecules (Hale et al., 2002; Eckert et al., 1999; Hale
and Haynes, 1992; Roep et al., 2002; Desser et al.,
1993). Munzig et al. (1994) did show that highly purified
bromelain protease F9 reduced the expression of CD44
to about 10 times more than the crude bromelain,
achieving about 97% inhibition of CD44 expression.
Roep et al. (Roep et al., 2002) reported that protease
treatment reduced expression of cell surface receptors
on T-cells and antigen-presenting cells. Previously,
reduction of CD44 expression on lymphocytes of
patients with multiple sclerosis during protease therapy
had been reported (Munzig et al., 1994; Stauder et al.,
1997; Hale and Haynes, 1992).
Roep et al. (2002) suggested that the generation of
soluble forms of adhesion molecules by proteolytic
cleavage could act as an additional benefit for
immonomudulatory function of protease treatment.
However, they noted that the quality of immune activation
plays an important role during chronic autoimmunity.
Earlier, animal models for rheumatoid arthritis and Type
1 diabetes protease treatment prevented or delayed the
Bromelain application in dermatological disorders:
Bromelain among other fruit extracts from apricots,
apples, peaches, pears, papayas, pomegranates,
cherries, kiwis, tangerines and oranges have been
described to play an important role in treating
dermatological disorders (Murad, 2003). Ozlen (1995)
has disclosed a cosmetic composition containing at
least one alpha-hydroxy acid, salicylic acid and at least
one digestive enzyme derived from fruit. Preferably the
digestive enzyme is a mixture of bromelain and papain.
Bromelain is disclosed as being typically obtained from
pineapple and papain is disclosed as being typically
obtained from dry papaya latex. The compositions are
allegedly useful for treating various cosmetic conditions
or dermatological disorders, such as lack of adequate
skin firmness, wrinkles and dry skin.
Conclusion: Bromelain being a plant extract, contains
various components such as proteinases, peroxidises,
phosphatises, protease inhibitors and organically bound
calcium whose ratio to each other might vary according
to soil composition, climate conditions during plant
growth, geographical location where the pineapple was
grown, pineapple variety and the process of extraction.
These factors might contribute to the variations of
bromelain’s pharmacological activities.
Proteolytic activity of bromelain has been shown to play
only a part in its pharmacological activity while other
factors such as immunomodulatory, hormone like
properties, fibrinolytic activity and uncharacterised
components such as CCS and CCZ complement
towards its pharmacological activity. However, there is
need for further investigation on the uncharacterised
Bromelain’s activity remains stable over a wide pH
range which explains why its activity has been found to
be effective over the entire gastrointestinal tract. Since it
is safe and non toxic, there is need to investigate how it
can be incorporated in foods. On our view, if successfully
incorporated in foods, it could become more acceptable
as a nutraceutical product than it now is.
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... [12] It has a medical usage as an anti-inflammatory agent in colonic inflammation, arthritis, soft tissue injuries, chronic pain, and asthma. [13] The primary component of bromelain is a sulfhydryl proteolytic fraction. It is rich in protease inhibitors, peroxidase, acid phosphatase, several protease inhibitors, and calcium. ...
... The anti-inflammatory action of bromelain depends on the proteolytic activity. [13] Papain, a cysteine protease isolated from the latex of papaya fruit, was used in the medical field. It is a proteolytic enzyme that has anti-bacterial, anti-inflammatory, and anti-oxidant properties. ...
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Objectives: Inflammatory bowel diseases (IBDs) are a multiple inflammatory status in small intestines and colon. Bromelain and Papain were cysteine proteases enzymes extracted from pineapple and papaya, and possess antioxidant and anti-inflammatory characteristics. Therefore, this comparative work aimed to examine the anti-inflammatory and antioxidant effect of bromelain and papain in intestinal inflammation of rats and to evaluate the most potent effect of both types of enzymes. Methods: Forty rats were used in this study (8 rats/group), G1: control group, G2: (Indo group) intestinal inflammation was induced by two doses of Indomethacin (7.5 mg/kg body weight) apart 24 h. G3: (Indomethacin + Bromelain) intestinal inflamed rats treated by oral dose of bromelain (1000 mg/kg/day). G4: (Indomethacin + Papain) intestinal inflamed rats treated by oral dose of papain (800 mg/kg/day). G5: (Indomethacin + Sulfasalazine) intestinal inflamed rats treated by oral dose of sulfasalazine (500 mg/kg/day). Oxidative stress and inflammatory markers were measured along with histological assessment. Results: Indomethacin-induced intestinal inflammation (in both Jejunum and Ileum) characterized by increased oxidative stress biomarkers: Xanthine oxidase, Catalase, Glutathione reductase, and Protein carbonyl and Inflammatory biomarkers: Tumor necrosis factor-α, Interleukin-10, Monocyte chemoattractant protein-1, Nuclear factor-kappa β, C-reactive protein, and Prostaglandin E2, as compared to control rats. On the other hand, administering either bromelain or Papain would effectively decrease symptoms of intestinal inflammation and modulate biomarkers of oxidative stress and pro-inflammatory cytokines. Conclusion: Comparing results revealed that bromelain showed the most potent protective effect and possesses an apparent role in protection against the development of intestinal inflammation.
... Crude bromelain (crude extract from pineapple) contains many cysteine and other components, including phosphatases, glucosidases, peroxidases, cellulases, glycoproteins, carbohydrates, nucleases, protease inhibitors, and organically bound calcium(De Lencastre Novaes , 2016& Tochi , 2008. ...
ABSTRACT The study aims at biosynthesis of nanoparticles from silver, iron, copper, and ammonium and aqueous and ethanolic extracts of two parts (core and pomace) of pineapple fruit and to assess the effectiveness of the prepared extracts and nanoparticles as antibacterial against two species of oral bacteria (Enterococcus faecalis and Streptococcus sanguis). Aqueous and ethanolic extracts were prepared for pomace and core of pineapple fruit in order to prepare nanoparticles of silver, iron, copper, and ammonium by adding solutions of silver nitrate, ferric sulfate, copper sulfate and ammonium sulfate. Black sediments formed for silver particles and a slight change in the brown color of the iron particles, and the copper particles appeared in turquoise color, and the ammonium particles appeared in a light pink color. The prepared nanoparticles were diagnosed using a (UV-visible) spectrophotometer, which showed absorption peaks of the nanoparticles from aqueous and ethanolic extracts for two pineapple parts (core & pomac) absorbance peaks were measured at (306 nm for Ag Nps , 348nm for Fe Nps , 198 nm for Cu Nps , 205 nm for NHNps) Infrared spectroscopy (FTIR) showed the effective groups of each of the aqueous and alcoholic extracts of pineapple parts, as well as the active groups of the prepared nanoparticles The most important aggregates for the two parts of the pineapple fruit (core, pomace) were: (O-H) bonding group between 3319-3000 cm and the (CH) bonding group the peak vibrated at 2933 and 1627- 1635 cm -1. As for the nanoparticles, strong peak vibrations involved groups of hydroxyl around the broad peak at 3348 cm. The strong band at 1635 cm -1 II corresponds to a 1-degree amine group with N - H bond. The peak is 1338 cm - 1 for silver nanoparticles and the Fe-O bond group in Fe3O4 shows characteristic peaks around 560-580 cm -1 and bending vibration of the group. The Fe-OH is between 3200-3600 cm-1 for iron nanoparticles and in the copper nanoparticles, a strong peak around 600-800 cm -1 corresponds to the Cu-O stretching vibration in CuO and a weak peak around 3400-3500 cm -1 is associated with the O-H stretching vibration of the surface hydroxyl groups on the copper nanoparticles and in the ammonium nanoparticles it showed a strong peak about 3300-3500 cm-1 corresponds to the N-H stretching vibration in NH3 . The Energy Dispersive X-Ray Analysis (EDX) device showed that concentration of the metal used for the synthesis of the nanoparticles, in addition to the presence or absence of impurities of other minerals, and the Scanning Electron Microscope (SEM) device was used to described the external shape of the formed nanoparticles and their size showed whether they were dispersed or in the form of agglomerations, where the silver nanoparticles appeared in an elliptical to spherical shape, and the iron nanoparticles appeared in a shape similar to the appearance of shattered rocks, while the copper nanoparticles were observed as smooth and highly crystalline in nature it has a great tendency to aggregate, and the ammonium particles appeared approximate to the shape of platelets. The antibacterial effect of prepared nanoparticles and aqueous and alcoholic extracts of pineapple fruit was studied by the turbidity measurement method, where three concentrations (1:1, 1:2, 1:4) of the aqueous extract and three concentrations of the ethanolic extracts (1:1, 1:10, 1:011) were used, for all prepared extracts and nanoparticles. The turbidity was measured by using a spectrophotometer at 530-nanometer wavelength, where the results showed that the aqueous extract of both parts (core, pomace) have a higher effect than the ethanolic extract of (core, pomace), and the results of silver nanoparticles from the aqueous and alcoholic extracts of (core, pomace) have the higher effect among the different prepared nanoparticles. The effect of III extracts and nanoparticles of iron, copper and ammonium, which also showed an inhibitory effect on bacteria, but in lower proportions than silver nanoparticles .
... Experimental and clinical research has shown that bromelain offers a variety of benefits, such as speeding up the healing of wounds, debriding burns, and reducing pain. In addition to anti-inflammatory effects, it also possesses anti-edema, anti-coagulant, and platelet aggregation inhibitory features [10,11]. The pH range of 4.5 to 9.5 is where bromelain is most active. ...
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Background Periodontitis is a persistent inflammatory condition. Eliminating the infection and reducing its risk factors are the first steps in treating periodontitis. When the anti-infective therapy is complete, there may still be deep periodontal pockets and prolonged inflammation. Surgical pocket reduction or elimination is indicated under these circumstances. We aimed to evaluate the effect of bromelain on bleeding on probing (BOP), gingival index (GI), and plaque index (PI) after pocket elimination surgery. Methods This double-blind randomized placebo-controlled trial included 28 candidates for pocket elimination surgery referred to the private office of a periodontist in Bandar Abbas, Iran, from April 18 to August 18, 2021. Patients’ general characteristics, such as age and sex, were recorded. Additionally, periodontal indices including BOP, PI, GI, and pocket probing depth (PPD) were evaluated in all subjects. All patients underwent pocket elimination surgery. Afterwards, they were randomized into two groups. The first group received 500 mg Anaheal (bromelain) capsules twice a day before meal for one week. The second group received placebo, prepared in similar shape and color by the same pharmaceutical company. BOP, PI, GI, and PPD were assessed four weeks after completion of the treatment course (five weeks after surgery). Results Four weeks after intervention, BOP was significantly lower with Anaheal compared to placebo (0% vs. 35.7%, P = 0.014). However, there was no significant difference in GI between groups (P = 0.120). Mean PI was lower (17.71 ± 2.12 vs. 18.28 ± 2.49) and mean PPD higher (3.10 ± 0.71 vs. 2.64 ± 0.45) in the Anaheal group, but the differences did not reach statistically significant levels (P = 0.520 and P = 0.051, respectively). Conclusions One-week treatment with Anaheal at a dose of 1 g/d after pocket elimination surgery resulted in significantly lower BOP compared to placebo. Trial registration Iranian Registry of Clinical Trials (IRCT), IRCT20201106049289N1. Registered 06/04/2021. Registered prospectively, .
... Since ancient times, bromelain has been used for treating bowel conditions, relieving osteoarthritis, improving the absorption of antibiotics, shortening labour and helping the body to get rid of fat. [7] However, there is limited literature to show its effect on angiogenesis, which is important for tissue regeneration and wound healing. Zebrafish has the potential to regenerate tissues such as heart, brain and muscle, which is not possible in mammals. ...
Background: Bromelain is a complex mixture of protease enzyme extract from the fruit or stem of the pineapple plant and it has a history of folk medicine use. It is known to have a wide range of biological actions and it is most commonly used as an anti-inflammatory agent, though scientists have also discovered its potential as an anticancer and antimicrobial agent, it has been reported to have positive effects on the respiratory, digestive, circulatory systems and potentially on the immune system. This study was designed to investigate the antidepressant potential of Bromelain in the chronic unpredictable stress (CUS) model of depression. Methods: We studied the antioxidant activity, and neuroprotective effect of Bromelain by analyzing the fear and anxiety behavior, antioxidants, and neurotransmitter levels, and also by analyzing the histopathological changes. Adult male Wistar albino rats were divided into 5 groups, Control; Bromelain; CUS; CUS + Bromelain, CUS + fluoxetine. Animals of the CUS group, CUS + Bromelain group, and CUS + Fluoxetine group were exposed to CUS for 30 days. Animals of the Bromelain group and CUS + Bromelain group were treated orally with 40mg/kg Bromelain throughout the period of CUS whereas, the positive control group was treated with fluoxetine. Results: Results showed a significant decrease in oxidative stress marker (lipid peroxidation), and the stress hormone cortisol, in Bromelain-treated CUS-induced depression. Bromelain treatment in CUS has also resulted in a significant increase in neurotransmitter levels, which indicates the efficacy of Bromelain to counteract the monamine neurotransmitter changes in depression by increasing their synthesis and reducing their metabolism. In addition, the antioxidant activity of Bromelain prevented oxidative stress in depressed rats. Also, hematoxylin and eosin staining of hippocampus sections has revealed that Bromelain treatment has protected the degeneration of nerve cells by chronic unpredictable stress exposure. Conclusion: This data provides evidence for the antidepressant-like action of Bromelain by preventing neurobehavioral, biochemical, and monoamine alterations.
... Since ancient times, bromelain has been used for treating bowel conditions, relieving osteoarthritis, improving the absorption of antibiotics, shortening labour and helping the body to get rid of fat. [7] However, there is limited literature to show its effect on angiogenesis, which is important for tissue regeneration and wound healing. Zebrafish has the potential to regenerate tissues such as heart, brain and muscle, which is not possible in mammals. ...
Full-text available
Objectives Diabetes mellitus is a chronic metabolic disease that is characterised by hyperglycaemia, altered lipids, carbohydrates and protein metabolism, and in the long-term, with eye, kidney, cardiovascular and neurological complications. Poor wound healing is one of the major complications faced by diabetes mellitus patients. Angiogenesis is critical for tissue regeneration and wound healing. Impaired angiogenesis may lead to poor blood flow to the wound and hence delayed wound healing. Hence, it is important to find an antidote to speed up wound healing. Hence, this study focuses on the proangiogenic potential of bromelain in the caudal fin regeneration of diabetic zebrafish. Materials and Methods Zebrafish were divided into control, Diabetic and Diabetic + Bromelain treated groups. Diabetes mellitus was induced using multiple doses of streptozotocin (350 mg/kg b.w./i.p.) on days 1, 3, 5, 12 and 19. Glucose levels were estimated on day 21 to confirm the induction of diabetes mellitus, and then, the caudal fin was amputated. After the amputation of the caudal fin, bromelain was administered orally at a dosage of 40 mg/kg b.w. on every alternate day for 15 days. Body weight, blood glucose level, total area and percentage of fin regeneration were observed on day 36. Images were compared and areas of regeneration were analysed with the help of Image J software. One-way analysis of variance followed by Tukey’s multiple comparison tests was used to analyse the data. Results A significant increase in the blood glucose level was observed in the diabetic group compared with control. A significant decrease in the percentage of tail regeneration and area of regeneration was observed in diabetic fishes compared to the control. Bromelain treatment has significantly increased the percentage and area of regeneration and significantly decreased the blood glucose level in the treatment group compared with the control. Conclusion The study confirms that bromelain can promote tissue regeneration; hence, it can be used to improve wound healing, which is one of the most common complications in diabetes mellitus.
... In addition, bromelain also has some anti-cancer effects and promotes cancer cells apoptosis [15,16]. In vivo and in vitro studies have shown that bromelain can reduce the symptoms of cardiovascular diseases [17,18]. Moreover, it has anticoagulant and fibrinolytic properties which have been used in the treatment of thromboembolism, as well as in the treatment of thrombophlebitis. ...
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Diosmin and bromelain are bioactive compounds of plant origin with proven beneficial effects on the human cardiovascular system. We found that diosmin and bromelain slightly reduced total carbonyls levels and had no effect on TBARS levels, as well as slightly increased the total non-enzymatic antioxidant capacity in the RBCs at concentrations of 30 and 60 µg/mL. Diosmin and bromelain induced a significant increase in total thiols and glutathione in the RBCs. Examining the rheological properties of RBCs, we found that both compounds slightly reduce the internal viscosity of the RBCs. Using the MSL (maleimide spin label), we revealed that higher concentrations of bromelain led to a significant decrease in the mobility of this spin label attached to cytosolic thiols in the RBCs, as well as attached to hemoglobin at a higher concentration of diosmin, and for both concentrations of bromelain. Both compounds tended to decrease the cell membrane fluidity in the subsurface area, but not in the deeper regions. An increase in the glutathione concentration and the total level of thiol compounds promotes the protection of the RBCs against oxidative stress, suggesting that both compounds have a stabilizing effect on the cell membrane and improve the rheological properties of the RBCs.
... Bromelain is an enzyme found in pineapple by-products with a broad commercial application (Sharma et al., 2019;Upadhyay et al., 2010). In addition, Tochi et al. (2008) indicated that the Bromelain absorption by cells depended on the percentage of inclusion in animal feed. ...
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Pineapple is a commodity and economic fruit with a high market potential worldwide. Almost 60 % of the fresh pineapple, such as peels, pulp, crowns and leaves, are agricultural waste. It is noteworthy that the waste has a high concentration of crude fibre, proteins, ascorbic acid, sugars and moisture content. The pineapple waste utilisation in animal feed has recently drawn the attention of many investigators to enhance growth performance and concomitantly reduce environmental pollution. Its inclusion in animal feed varies according to the livestock, such as feed block, pelleted or directly used as a roughage source for ruminants. The pineapple waste is also fermented to enrich the nutrient content of poultry feed. To date, the inclusion of pineapple waste in animal feed is optimistic only not for livestock but also for farmed fish. Indeed, it is an ideal strategy to improve the feed supply to the farm. This paper aims to overview the source, nutritional composition, and application of pineapple waste in animal feed. The recent findings on its effect on animal growth performance, nutrition and disease control are discussed comprehensively and summarised. The review also covers its benefits, potential impacts on sustainable farming and future perspectives.
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Bromelain is a proteolytic enzyme derived from the pineapple plant (Ananas comosus). Bromelain can be extracted from pineapple stems and fruits. Additionally, it can be derived from pineapple wastes such as the core, crown, and peel. Various extraction and purification methods such as reverse micellar system, aqueous two-phase system, chromatographic techniques, and membrane filtration have been used in order to produce high-quality bromelain. Bromelain has been used clinically since 1876 and was first introduced as a therapeutic agent in 1957. Bromelain has gained increasing acceptance and compliance among patients as a phytotherapeutic drug due to its safety and lack of undesirable side effects. Bromelain is regarded as a nutrient that promotes wound healing due to the presence of several closely related proteinases that exhibit anti-inflammatory, fibrinolytic, and debridement properties.
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Pruritus is a common and distressing skin disorder and treatment of itch is a daily problem for millions of people. Available therapies are ineffective and there is an urgent need for new topical treatments to relieve itch. Studies were undertaken to identify the optimal concentration of a natural therapeutic for the relief of itch and to assess the safety of this agent in dermal application with six volunteers. In the initial study, six volunteers with self-diagnosed atopic dermatitis applied a lotion containing concentrations ranging from 5 to 25 weight percent of 1200 Gelatin Dissolving Units (GDU) bromelain to their skin and noted any discomfort caused to the area and the amount of symptomatic relief that was obtained. Based on this study, 15 weight percent of 1200 GDU bromelain suspended in lotion was selected for further testing. For the safety study, a total of thirty subjects were randomized into three pools and participants in each pool applied the lotion to their arms, backs, or legs on a daily basis. After four weeks, all the participants had completed the study and none had reported an adverse event. The lotion was found to be safe and effective when applied topically on a daily basis.
In Hawaii, people experience high sunlight exposure, contributing to an increased risk of sunburn. Additionally, most parts of pineapples are discarded, contributing to food waste and microbial spoilage, and we wanted to determine whether bromelain sourced from pineapple could be repurposed as a treatment to protect skin cells from UV damage. Bromelain from pineapple can be used to treat symptoms of sunburn, which occurs when UV rays damage the DNA in cells. Therefore, we hypothesized that bromelain extracted from various parts of the pineapple (crown, flesh, skin, and stem) would protect the skin cells from cell death caused by UV damage. Also, we expected bromelain from the stem, which is known to contain the highest concentration of bromelain, to be the most effective in protecting skin cells from UV-induced cell death. The effect of purified bromelain powder on skin cell survival was analyzed using the PrestoBlue cell viability assay to compare the protective effect of pineapple extracts on UV-induced cell death. We also examined the expression level of tumor necrosis factor-α (TNF-α), which is a pro-inflammatory marker. The results indicated that bromelain protected skin cells from UV-dependent cell death and increased the mRNA expression level of TNF-α. Additionally, bromelain had a more protective effect when it was used as a pre-treatment method than post-treatment. Overall, this study suggests that bromelain may provide some protection to the skin from UV-induced cell death. Thus, further studies may investigate its application in sunscreen products to improve protection.
Oral hydrolytic enzymes in combination with rutosid have been applied in MS patients for more than 20 years. We investigated whether immunological alterations in MS patients are influenced by enzyme treatment. We determined the phenotypes of specific lymphocytic antigens in 12 patients with relapsing-remitting MS, who were known to be under long-term treatment with oral hydrolytic enzymes (Phlogenzym®). Matched untreated (i.e., only treated for symptoms) MS patients (n = 18) and healthy volunteers (n = 10) served as controls. For phenotyping, the following lymphocytic antigens were measured: CD4, CD8, CD3, CD2, CD19, CD56, CD14, CD45, CD45RA, CD45RO, CD25, CD54 and HLA-DR. Tests were carried out with a panel of different fluorescence-conjugated murine monoclonal antibodies and subsequent two color flow-cytometry. Data is expressed as percentage gated cells. Symptomatically treated patients had increased CD4, CD19, CD2 and CD45RO, CD54 and CD56. These changes were influenced by hydrolytic enzymes in the following manner: CD8 was markedly decreased; CD4, CD2, CD25, CD-45-RO, CD-45RA, CD56 slightly decreased. Furthermore, a statistically significant decrease was found for CD45 and CD54. From these results the conclusion can be drawn that positive clinical findings in MS patients under oral hydrolytic enzymes are causatively linked to a decrease in inflammatory activity.
It has recently been demonstrated that proteolytic enzyme treatment modulates certain immune-mediated diseases. We have, therefore, studied the effect of administration of a protease mixture in the NOD mouse, an elegant animal model for autoimmune insulin-dependent diabetes mellitus (IDDM). Female NOD mice were fed proteolytic enzymes from age 6 weeks to 10 weeks, within the subclinical phase of IDDM. Once a week animals received intragastrically 1 mg Phlogenzym® (n = 10 mice) or 0.5 mg Phlogenzym® (n = 10) in 0.5 ml saline or saline only (n = 10). Mice were followed for development of IDDM up to week 23. At week 21, all control animals were diabetic, whereas 25% of the treated mice were still normoglycemic at the end of the observation period. No significant appearance of autoantibodies against either isoform of the important islet cell antigen glutamic acid decarboxylase (GAD), GAD65 and GAD67, was observed in the mouse sera as determined by a highly sensitive radioimmunoassay. The histopathological examination of pancreatic islets showed signs of insulitis in all mice with a tendancy of milder insulitis in the protease-treated groups.
Three groups of randomly selected mice were immunized and boosted with Type II collagen; age-matched nonimmunized controls were maintained. Beginning on day 28, groups were given 120 mg/kg oral Phlogenzym® twice daily, 40 mg/kg oral ibuprofen twice daily, or no therapy. Swelling of the footpads, measured with a tensioning caliper generally appeared on day 21, and was identical in the three immunized groups until day 31; subsequently, mice given Phlogenzym® or ibuprofen had significantly less swelling than the untreated mice, with no difference between the two therapies. At sacrifice, there was severe joint degeneration in the untreated groups at 42 and 49 days, with ankylosis in 3 of 8 untreated mice examined at 49 days. Joint degeneration was moderate at day 42 and moderate to severe at day 49 in the ibuprofen-treated mice, but mild at day 42 and generally mild at day 49 in Phlogenzym®-treated mice (chi-squared = 5.8, p < 0.05). Computer morphometry revealed an average cartilage thickness of 720 μm in normals, 630 μm in Phlogenzym®-treated diseased mice, 380 μm in ibuprofen-treated diseased mice, and 290 μm in untreated diseased mice (F = 9.8, p < 0.01). Radiographic scores correlated with the pathologic scores. We conclude that Phlogenzym® protects articular cartilage significantly better than ibuprofen in this murine model of rheumatoid arthritis, despite equal antiinflammatory potency.
latory effects. In this study, we show for the first time that extracellular proteases may also block signal transduction. We show that bromelain, a mixture of cysteine proteases from pineapple stems, blocks activation of ERK-2 in Th0 cells stimulated via the TCR with anti-CD3e mAb, or stimulated with combined PMA and calcium ionophore. The inhibitory activity of bromelain was dependent on its proteolytic activity, as ERK-2 inhibition was abrogated by E-64, a selective cysteine protease inhibitor. However, inhibitory effects were not caused by nonspecific proteolysis, as the protease trypsin had no effect on ERK activation. Bromelain also inhibited PMA-induced IL-2, IFN-g, and IL-4 mRNA accumulation, but had no effect on TCR-induced cytokine mRNA production. This data suggests a critical requirement for ERK-2 in PMA-induced cytokine production, but not TCR-induced cytokine production. Bromelain did not act on ERK-2 directly, as it also inhibited p21ras activation, an effector molecule upstream from ERK-2 in the Raf-1/MEK/ERK-2 kinase signaling cascade. The results indicate that bromelain is a novel inhibitor of T cell signal transduction and suggests a novel role for extracellular proteases as inhibitors of intracellular signal transduction pathways. The Journal of Immunology, 1999, 163: 2568 -2575.
First introduced as a therapeutic compound in 1957, bromelain's actions include: (1) inhibition of platelet aggregation; (2) fibrinolytic activity; (3) anti-inflammatory action; (4) anti-tumor action; (5) modulation of cytokines and immunity; (6) skin debridement properties; (7) enhanced absorption of other drugs; (8) mucolytic properties; (9) digestive assistance; (10) enhanced wound healing; and (11) cardiovascular and circulatory improvement. Bromelain is well absorbed orally and available evidence indicates that it's therapeutic effects are enhanced with higher doses. Although all of its mechanisms of action are still not completely resolved, it has been demonstrated to be a safe and effective supplement. (Alt Med Rev 1996;1(4):243-257)
Objective: To compare the short-term efficacy and tolerability of an oral enzyme therapy with the NSAID diclofenac in patients with symptomatic osteoarthritis of the knee (gonarthritis). Methods: In a double-blind clinical trial, 73 patients with painful gonarthritis were randomised to receive 3 weeks of treatment with an oral enzyme preparation (Phlogenzym®) containing bromelain, trypsin and rutin (n = 36), or the NSAID diclofenac (n = 37). Efficacy was primarily evaluated using the Lequesne index (measuring pain and function of the affected knee). Other investigations included assessment of pain symptoms using a visual analogue scale (VAS), global assessment of efficacy and tolerability (by both patients and one physician), and various laboratory parameters. Patients were evaluated at baseline, at weekly intervals throughout the 3-week treatment period, and at 7 weeks (i.e. 4 weeks after discontinuing therapy). Results: The Lequesne index improved continuously in both groups: from 13.56 at baseline to 3.10 after 3 weeks (end of therapy) to 2.05 at 7 weeks (follow-up) in the enzyme group, and from 14.04 to 3.50 to 2.24, respectively, in the diclofenac group. Statistical evaluation showed the treatment groups to be equivalent; the lower bound of the 95% confidence interval of the Mann-Whitney estimator was above 0.44 (the limit for equivalence) at all time points. Global assessment of efficacy and tolerability of the drugs was ‘very good’ or ‘good’ for the majority patients. Conclusions: Short-term evaluation indicates that oral enzymes may be considered an effective and safe alternative to NSAIDs such as diclofenac in the treatment of painful gonarthritis.