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Therapeutic Application of Pineapple Protease (Bromelain): A Review

Authors:

Abstract

Bromelain (EC 3.4.22.32) 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
513
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,
1
Jiangnan University, Wuxi 214122, PR China
Pwani University College - Formerly Kilifi Institute of Agriculture, P.O. Box: 195, Kilifi, Kenya, East Africa
2
Abstract: Bromelain (EC 3.4.22.32) 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
Introduction
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
2
degree the Th cytokines IL-2 and induced interferon-
1
gamma (IFN-() via modulation of the extracellular
Tochi et al.: Bromelain’s Pharmacology
514
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.
-1-
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
515
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
516
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
2
(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.
k
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
517
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
discontinued.
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
components.
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.
References
Abbey, D.M. and F.C. Knoop, 1979. Effect of
chlorpromazine on the secretory activity of
Escherichia coli heat-stable enterotoxin. Infect
Immun., 26: 1000-1003.
Tochi et al.: Bromelain’s Pharmacology
518
Ahle, N.W. and M.P. Hamlet, 1987. Enzymatic frostbiteEmancipator, S., S.R. Chintalacharuvu, N. Urankar Nagy,
eschar debridement by bromelain. Ann. Emerg. Med C. Petersilge and G. Stauder, 1997. Effects of oral
16: 1063-1065. enzymes in collagen II induced arthritis in mice. Int.
Akhtar, N.M., R. Naseer, A.Z. Farooqi, A. Wajahat and M. J. Immunotherapy, 13: 67-74.
Nazir, 2004. Oral enzyme combination versus Engwerda, C.R., D. Andrew, A. Ladhams and T.L. Mynott,
diclofenac in the treatment of osteoarthritis of the2001. Bromelain modulates T cell and B cell
knee - a double-blind prospective randomizedimmune responses in vitro and in vivo. Cell.
study. Clin. Rheumatol., 23: 410-415. Immunol., 210: 66-75.
Ammon, H.P., 2002. Boswellic acids (components ofField, M., 1981. Secretion of electrolytes and water by
frankincense) as the active principle in treatment ofmammalian small intestine. In: Jonhson L.R., (Ed.).
chronic inflammatory disease. Wien. Med.Physiology of gastrointestinal tract. New York:
Wochenschr., 152: 373-378. Raven, pp: 963-982.
Balakrishnan, V., A. Hareendran and N.C. Sukumaran,Gaciong, Z., L. Paczek, K. Bojakowski, K. Socha, M.
1981. Double-blind cross-over trial of an enzymeWisniewski and A. Heidland, 1996. Beneficial effect
preparation in pancreatic steatorrhea. J. Assoc.of proteases on allograft arteriosclerosis in a rat
Phys. Ind., 29: 207-209. aortic model. Nephrol. Dial. Transplant., 11: 987-
Batkin, S., S.J. Taussig and J. Szekerczes, 1985.989.
Inhibition of tumour growth in vitro by bromelain, anGoldstein, N., S. Taussig, J. Gallup and V. Koto, 1975.
extract of the pineapple (Ananas comosus). PlantaBromelain as a skin cancer preventive in hairless
medica, 6: 538-539. mice. Hawaii Med. J., 34: 91-94.
Batkin, S., S.J. Taussig and J. Szekerczes, 1988b.Grabowska, E., K. Eckert, I. Fichtner, K. Schulze-Forster
Antimetastatic effect of bromelain with or without itsand H.R. Maurer, 1997. Bromelain proteases
proteolytic and anticoagulant activity,. J. Cancer Res. suppress growth, invasion and lung metastasis of
Clin. Oncol., 114: 507-508. B16F10 mouse melanoma cells. Int. J. Oncol., 11:
Batkin, S., S.J. Taussig and J. Szekerczes, 1988a.243-248.
Modulation of pulmonary metastasis (LewisGreenberg, R.N., F. Murad, B. Chang, D.C. Robertson
lung carcinoma) by bromelain and extract of theand R.L. Guerrant, 1980. Inhibition of Escherichia
pineapple stem (Ananas comosus). Cancer Invest.,coli heat-stable enterotoxin by indomethacin and
6: 233-234. chlorpromazine. Infect Immun., 29: 908-913.
Chandler, D.S. and T.L. Mynott, 1998. Bromelain protects Guandalini, S., A. Fasano, M.C. Rao, A. Ferola, G.
piglets from diarrhoea caused by oral challengeMigliavacca and A. Rubino, 1984. Effects of
with K88 positive enterotoxigenic Escherichia coli.loperamide on intestinal ion transport. J. Pediatr.
Gut., 43:196-202. Gastroenterol. Nutr., 3: 593-601.
Cohen, G., 1964. Bromelain therapy in rheumatoidGuandalini, S., A. Fasano, M. Migliavacca, G.
arthritis. Pennsylvania Med. J., 67: 127-131. Marchesano, A. Ferola and A. Rubino, 1987. Effects
Cooreman, W.M., S. Scharpe, J. Demeester and A.of berberine on basal and secretagogue-modified
Lauwers, 1976. Bromelain, biochemical andion transport in rabbit ileum in vitro. J. Pediatr.
pharmacological properties. Pharm. Acta Helv., 4:Gastroenterol. Nutr., 6: 953-960.
73-79. Hale, L.P., J.F. David and F.S. Herman, 2006. Oral
Cravioto, A., R.E. Reyes, R. Ortega, G. Fernandez, R.immunogenicity of the plant proteinase bromelain.
Hernandez and D. Lopez, 1988. Prospective study of Int. Immunopharmacol., 6: 2038-2046.
diarrheal disease in cohort of rural MexicanHale, L.P., 2004. Proteolytic activity and immunogenicity
children: Incidence and isolated pathogens duringof oral bromelain within the gastrointestinal tract of
the first two years of life. Epidemiol. Infect, 101: 123- mice. International Immunopharmacol., 4: 255- 264.
134. Hale, L.P., P.K. Greer, C.T. Trinh and M.R. Gottfried,
Darshan, S. and R. Doreswamy, 2004. Patented anti-2005. Treatment with oral bromelain decreases
inflammatory plant drug development fromcolonic inflammation in the IL-10-deficient murine
traditional medicine. Phytother. Res., 18: 343-357. model of inflammatory bowel disease. Clin.
Desser, L.A., E. Rehberger, E. Kokron and W. Paukovits, Immunol., 116: 135-142.
1993. Cytokine synthesis in human peripheralHale, L.P. and B.F. Haynes, 1992. Bromelain treatment
blood mononuclear cells after oral administration ofof human T cells removes CD44, CD45RA,
poly-enzyme preparations. Oncol., 50: 403-407. E2/MIC2, CD6, CD7, CD8 and Leu 8/LAM1 surface
Eckert, K., E. Grabwska, R. Stange, U. Schneider, K.molecules and markedly enhances CD2- mediated
Eschmann and H.R. Maurer, 1999. Effects of oralT cell activation. J. Immunol., 149: 3809-3816.
bromelain administration on the impairedHale, L.P., P.K. Greer and G.D. Sempowski, 2002.
immunocytotoxicity of mononuclear cells fromBromelain treatment alters leukocyte expression of
mammary tumour patients. Oncol. Rep., 6: 1191-cell surface molecules involved in cellular adhesion
1199. and activation. Clin. Immunol., 104: 183-190.
Tochi et al.: Bromelain’s Pharmacology
519
Hale, L.P., P.K. Greer, C.T. Trinh and C.L. James, 2005. Manhart, N., R. Akomeah, H. Bergmeister, A. Spittler, M.
Proteinase activity and stability of natural bromelain
preparations. Int. Immunopharmacol., 5: 783-793.
Heinecke, R.M. and W.A. Gortner, 1957. Stem bromelain,
a new protease preparation from pineapple plants.
Economic Botany, 11: 225-234.
Heinicke, R.M., M. Van der Wal and M.M. Yokoyama,
1972. Effect of bromelain on human platelet
aggregation. Experientia., 28: 844-845.
Holmgren, J., S. Lange and I. Lonnroth, 1978. Reversal
of cyclic AMP-mediated intestinal secretion in mice
by chlorpromazine. Gastroenterology., 75: 1103-
1108.
Honn, K.V., 1983. Inhibition of tumor cell metastasis by
modulation of the vascular prostacyelin
/thromboxane A2 system. Clin. Exp. Metastasis, 1:
103-114.
Izaka, K.I., M. Yamada, T. Kawano and T. Suyama, 1972.
Gastrointestinal absorption and anti-inflammatory
effect of bromelain. Jpn. J. Pharmecol., 4: 519-534.
Jaber, R., 2002. Respiratory and allergic diseases:
From upper respiratory tract infections to asthma.
Prim. Care, 2: 231-261.
Janzekovic, Z., 1970. A new concept in the early excision
and immediate grafting of burns. J. Trauma. 10:
1103-1108.
Kane, S. and M.J. Goldberg, 2000. Use of bromelain for
mild ulcerative colitis. Ann. Int. Med., 132: 680.
Kelly, G.S., 1996. Bromelain: A literature review andMurad, H., 2003. Method of treating dermatological
discussion of its therapeutic applications. Altern.
Med. Rev., 1: 243-257.
Klaue, P., G. Dilbert and G. Hinke, 1979. In: Bromelain:
Biochemistry, pharmacology and medical use.
Cellular and Molecular Life Sciences 58: 1234-
1245.
Klein, G. and W. Kullich, 2000. Short term treatment of
painful osteoarthritis of the knee with oral enzymes:
A randomised, double - blind study versus
diclofenac. Clin. Drug Invest., 19: 15-23.
Knill - Jones, R.P., H. Pearce and J. Batten, 1970.
Comparative trial of Nutrizym in chronic pancreatic
insufficiency. Br. Med. J., 4: 21.
Lemay, M., M.A. Murray, A. Davies, H. Roh-Schmidt and
R.K. Randolph, 2004. In vitro and ex vivo
cyclooxygenase inhibition by a hops extract,. Asian
Pac. J. Clin. Nutr., 13: S110.
Levine, M.M., J.B. Kaper, R.E. Black and M.L. Clements,
1983. New knowledge on pathogenesis of bacterial
enteric infections as applied to vaccine
development. Microbiol. Rev., 47: 510-550.
Lotti, T., V. Mirone, C. Imbimbo, F. Corrado, G. Corrado,
F. Garofalo and I. Scaricabarozzi, 1993. Controlled
clinical studies of nimesulide in the treatment of
urogenital inflammation. Drugs 46 Suppl, 1: 144-
146.
Ploner and E. Roth, 2002. Administration of
proteolytic enzymes bromelain and trypsin diminish
the number of CD4+ cells and interferon-gamma
response in Peyer's patches and spleen in
endotoxemic balb/c mice. Cell. Immunol., 2: 113-
119.
Maurer, H.R., M. Hozumi, Y. Honma and J. Okabe-Kado,
1988. Bromelain induces the differentiation of
leukemic cells in vitro: An explanation for its
cytostatic effects? Planta Medica, 54: 377-381.
Maurer, H.R., 2001. Bromelain: Biochemistry,
pharmacology and medical use. Cell. Mol. Life Sci.,
58: 1231-1245.
Metzig, C., E. Grabowska, K. Eckert, K. Rehse and H.R.
Maurer, 1999. Bromelain proteases reduce human
platelet aggregation in vitro, adhesion to bovine
endothelial cells and thrombus formation in rat
vessels in vivo. In vivo, 13: 7-12.
Miller, J.G., H.R. Carruthers and D.A. Burd, 1992. An
algorithmic approach to the management of
cutaneous burns. Burns., 18: 200-211.
Monafo, W.W., 1974. Tangential excision. Clin. Plast
Surg., 1: 591-601.
Munzig, E., K. Eckert, T. Harrach, H. Graf and H.R.
Maurer, 1994. Bromelain protease F9 reduces the
CD44 mediated adhesion of human peripheral
blood lymphocytes to human umbilical vein
endothelial cells. FEBS Lett., 351: 215-218.
disorders with fruit extracts. In: Patent, U.S. (Ed.).
http://www.freepatentsonline.com/. U.S., 1-38.
Mynott, T.L., R.K. Luke and D.S. Chandler, 1996. Oral
administration of protease inhibits enterotoxigenic
Escherichia coli receptor activity in piglet small
intestine. Gut., 38: 28-32.
Mynott, T.L., S. Guandalini, F. Raimondi and A. Fasano,
1997. Bromelain prevents secretion caused by
Vibrio cholerae and Escherichia coli Enterotoxins in
rabbit Ileum In vitro. Gastroenterol., 113: 175-184.
Mynott, T.L., A. Ladhams, P. Scarmato and C.R.
Engwerda, 1999. Bromelain, from pineapple stems,
proteolytically blocks activation of extracellular
regulated kinase-2 in T cells. J. Immunol., 163:
2568-2575.
Nada, Y., K. Sasaki, M. Nozaki, M. Takeuchi, X. Chen and
H. Nakazawa, 1998. The effect of early burn wound
excision on regional gastric blood flow in rats.
Burns, 24: 519-524.
Nieper, H.A., 1978. Effect of bromelain on coronary heart
disease and angina pectoris. Acta Med. Empirica.,
5: 274-278.
Ozlen, S.N., 1995. Cosmetic composition containing
alpha hydroxyacids, salicyclic acid and enzyme
mixture of bromelain and papain. In: Patent, U.S.
(Ed.). http://www.freepatentsonline.com/. United
States: Longevity Network Ltd. Handerson, Nev 1-6.
Tochi et al.: Bromelain’s Pharmacology
520
Peckoldt, T. and G. Peckoldt., In: Taussig, S.J. and S.Stauder, G., B. Donnerstag, U. Baumhackl and E.
Batkin, 1988. Bromelain, the enzyme complex of
pineapple (Annanus comosus) and its clinical
application: An update. J. Ethnopharmacol., 22: 191-
203.
Prasanna, M., K. Singh and P. Kumar, 1994. Early
tangential excision and skin grafting as a routine
method of burn wound management: An experience
from a developing country. Burns., 20: 446-450.
QIMR, 2005. Pineapple stems that show anti-tumour
activity. Medical Research News: The Queensland
Institute of Medical Research.
Roep, B.O., N.K. van den Engel, A.G.S. van Halteren, G.
Duinkerken and S. Martin, 2002. Modulation of
autoimmunity to beta-cell antigens by proteases.
Diabetologia., 45: 686-692.
Roselli, M., M.S. Britti, H.I. Le, H. Marfaing, W.Y. Zhu and
E. Mengheri, 2007. Effect of different plantwirkung beim karzinom. Krebsgeschehen 8: 81-87.
extracts and natural substances (PENS) against
membrane damage induced by enterotoxigenic
Escherichia coli K88 in pig intestinal cells. Toxicol.
in vitro., 21: 224-229.
Rosenberg, L., O. Lapid, A. Bogdanov-Berezovsky, R.
Glesinger, Y. Krieger, E. Silberstein, A. Sagi, K.
Judkins and A.J. Singer, 2004. Safety and efficacy of
a proteolytic enzyme for enzymatic burn
de´bridement: A preliminary report. Burns., 30: 843-
850.
Rovenska, E., K. Svik, M. Stancikova and J. Rovensky,
2001. Inhibitory effect of enzyme therapy and
combination therapy with cyclosporin A on collagen-
induced arthritis. Clin. Exp. Rheumatol., 19: 303-
309.
Salisbury, R.E., 1990. In: Thermal burns. McCarthy J.G.,
(Ed.). Plastic surgery, 1: 787-830.
Sato, M., T. Narisawa, M. Sano, T. Takahashi and A.
Goto, 1983. Growth inhibition of transplantable
murine colon adenocarcinoma 38 by indomethacin.
J. Cancer Res. Clin. Oncol., 106: 21-36.
Secor, E.R. Jr., W.F. Carson IV, M.M. Cloutier, L.A.
Guernsey, C.M. Schramm, C.A. Wu and R.S. Thrall,
2005. Bromelain exerts anti-inflammatory effects in
an ovalbumin-induced murine model of allergic
airway disease. Cell. Immunol., 237: 68-75.
Sheridan, R.L., R.G. Tompkins and J.F. Burke, 1994.
Management of burn wounds with prompt excision
and immediate closure (see comments). J.
Intensive Care Med., 9: 6-17.
Sheridan, R., J. Remensnyder, K. Prelack, L. Petras and Modulation of colonic gene expression of inducible
M. Lydon, 1998. Treatment of the seriously burned
infant. J. Burn Care Rehabil., 19: 115-118.
Smith, H.W. and M.A. Lingood, 1982. Further
observations on Escherichia coli enterotoxins with
particular regard to those produced by atypical piglet
strains and by calf and lamb strains: The
transmissible nature of these enterotoxins and of a
k antigen possessed by calf and lamb strains. J.
Med. Microbiol., 5: 243-250.
Buschmans, 1997. Use of oral enzymes in multiple
sclerosis: Phenotyping of peripheral blood
lymphocytes from MS patients under long-term
treatment with orally administered hydrolytic
enzymes. Int. J. Immunotherapy, 13: 135-137.
Targoni, O.S., M. Tary-Lehmann and P.V. Lehmann,
1999. Prevention of murine EAE by oral hydrotic
enzyme treatment. J. Autoimmune., 12: 191-198.
Taussig, S.J. and H.A. Nieper, 1979. Bromelain: Its use
in prevention and treatment of cardiovascular
disease, present status. J IAPM, 6: 139-151.
Taussig, S.J. and S. Batkin,1988. Bromelain, the enzyme
complex of pineapple (Ananas comosus) and its
clinical application: An update. Ethnopharmacol.,
22: 191-203.
Taussig, S.J. and N. Goldstein, 1976. Bromelain -
Thomson, A.B., M. Keelan, A. Thiesen, M.T. Clandinin, M.
Ropeleski and G.E. Wild, 2001. Small bowel review:
normal physiology. Part 1. Digestive Dis, Sci., 46:
2567-2587.
Thornhill, S.M. and A.M. Kelly, 2000. Natural treatment of
perennial allergic rhinitis, Altern. Med. Rev., 5: 448-
454.
Tilwe, G.H., S. Beria, N.H. Turakhia, G.V. Daftary and W.
Schiess, 2001. Efficacy and tolerability of oral
enzyme therapy as compared to diclofenac in active
osteoarthrosis of knee joint: An open randomized
controlled clinical trial. J. Assoc. Physicians India.,
49: 617-621.
Turjman, N., G.S. Gotterer and T.R. Hendrix, 1978.
Prevention and reversal of cholera enterotoxin
effects in rabbit jejunum by nicotinic acid. J. Clin.
Invest., 61: 1155-1160.
Uhlig, G., 1981. Schwellungsprophylaxe nach exogenen
Trauma. Z Allgemeinmed, 57: 127-131.
Vogler, W., 1988. Enzymtherapie beim Weichteilr-
heumatismus. Natur - Ganzheits - Med., 1: 27.
Walker, A.F., R. Bundy, S.M. Hicks and R.W. Middleton,
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: 681-686.
Wen, S., T.H.W. Huang, G.Q. Li, J. Yamahara, B.D.
Roufogalis and Y. Li, 2006. Bromelain improves
decrease in defecation in postoperative rats:
nitric oxide synthase. Life Sci., 78: 995-1002.
White, R.B., L. Lowrie, S.S. Iskandar, M.E. Lamm and
S.N. Emancipator, 1991. Target enzyme therapy of
experimental glomerulonehpritis in rats. J. Clin.
Invest., 87: 1819-1827.
Wiest-Ladenburger, U., W. Richter, P. Moeller and B.O.
Boehm, 1997. Protease treatment delays diabetes
onset in diabetes - prone nonobese diabetic (NOD)
mice. Int. J. Immunotherapy., 13: 75-78.
... Microorganisms has the presence of alkaline phosphatase in their periplasmic space that is external to the cell membrane getting released during either starvation or in the presence of phosphate molecule in the media, which has higher rate of activity, resistance to inactivation, denaturation and degradation (Junior et al., 2008). Micro organisms such as E. coli., Bacillus sp, Pseudomonas sp, Xanthomonas sp, Enterobacter sp, Acidovorans sp, Azotobacter sp, Arthrobactersp, Acetobacter sp, Vibrio sp, Aspergillus sp Chladosporium sp, Mucor spp, Fusarium sp, Curvularia sp (Von Tigerstrom., 1984, Prada, Curtze and Brenchley., 1996, Angkawidjaja et al., 2006, Sharipova, Balaban and Mardanova, 1998, Micrococcus sodonensis (Glew and Heath, 1971), Alkophilic bacterium (Nomoto et al., 1988), Alcaligenes faecalis (Behera et al., 2017), Haloarcula marismortui (Goldman et al., 1990),Sphingobacterium antarcticus (Chattopadhyay et al., 1995), Geobacillus thermodenitrificans T2 (Zhang et al., 2008), Thermotoga neapolitana (Dong and Zeikus, 1997), Bacillus thuringiensis MB497 (Ambreen et al., 2020), Pyrococcus abyssi (Zappa et al., 2001), Pencillium expansum (Dahot et al., 1986), Neurospora crassa (Pereira et al., 1995), Anabaena oryzae (Singh et al., 2006), Chlorella vulgaris (Durrieu and Tran-Minh, 2002) has the capacity to produce this enzyme. Alkaline phosphatase present in humans is categorized into four groups depending on the location where it is predominately expressed is given in table 1. ...
... • Effects of Bromelain on Diarrhoea: Bromelain neutralizes some of the effects of specific intestinal pathogens like Vibrio cholera and Escherichia coli, and their enterotoxins are responsible for causing diarrhoea in animals (Gomes et al., 2016;Nipa Tochi et al., 2008). Bromelain interacts with intestinal secretory signalling pathways, including adenosine 3: 5-cyclic monophosphatase, guanosine 3: 5 -cyclic monophosphatase, and calcium-dependent signalling cascades. ...
Chapter
Tannin acyl hydrolase is also known as tannase. Tannase acts upon ester and depside linkages in gallotannins,ellagitannins, complex tannins and gallic acid esters to gallic acid that finds application in the food processing industry due to its antioxidant activity. Tannins are present in every part of plant in the form of secondary metabolite. The animal sources of tannase include bovine intestine and ruminal mucus. Although tannase has a long history with numerous publications, it is still considered as an expensive industrial enzyme. Tannase derived from microorganisms have wide applications in various industries, due to their abundance and ease to produce. Organisms like bacteria, fungi and yeast produce tannase enzyme which can be used for various applications. The fungi isolated from various sources produce more tannase enzyme. There are various fermentation and purification processes to produce tannase enzyme using microorganisms.It is extensively used in food, animal feed, pharmaceutical, beverage, brewing, tannery and chemical industry. Main application of tannase is elaboration of instantaneous tea, acorn wine and gallic acid production. It is also used as clarifying agent in juice and coffee flavored beverages. Gallic acid is used in pharmaceutical industry as an intermediary compound for the synthesis of trimethoprim antibiotic. In chemical industry it is used as substrate for the chemical or enzymatic synthesis of propylgallate and other antioxidant compounds used in food processing industry. This chapter deals about the application of tannase in various fields. Keywords:Tannase, Tannin, Gallic acid, Food Industry, Pharmaceutical, Brewery, Tannery.
... Bromelin merupakan komponen utama dari enzim proteolitik sulfhidril. Bromelin juga mengandung peroksidase, asam fosfatase, sebagian inhibitor protease dan mampu berikatan dengan kalsium (Tochi et al. 2008). Bromelin terdapat dalam buah maupun limbah nanas. ...
... Enzim ini stabil pada rentang pH 4.5-9.8 (Tochi et al. 2008, Bhattacharyya 2008. Aktivitas bromelin optimum pada suhu 50 °C dan aktivitas nya menurun jika berada pada suhu diatas suhu 50 °C. ...
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Enzim bromelin adalah enzim proteolitik yang memiliki kemampuan menghidrolisis protein sehingga bisa berperan sebagai antibakteri. Enzim bromelin dapat diisolasi dari kulit, buah, bonggol Nanas (Ananas comosus (L.) Merr ). Tujuan penelitian ini adalah untuk mendapatkan konsentrasi enzim bromelin dari kulit dan bonggol buah Nanas dalam menghambat pertumbuhan Staphylococcus aureus. Bromelin diisolasi dengan cara ekstraksi dengan buffer pospat, dipurifikasi dengan ammonium sulfat 60%. Uji aktivitas antibakteri enzim bromelin dari kulit dan bonggol Nanas terhadap bakteri Staphylococcus aureus dilakukan secara invitro menggunakan difusi cakram dengan mengukur zona hambat. Konsentrasi enzim bromelin yang digunakan adalah 1 %, 2%, 3% dan 4% dengan antibiotik kloramfenikol sebagai kontrol positif. Enzim bromelin dari kulit dan bonggol Nanas pada konsentrasi 4% menghambat pertumbuhan Staphylococcus aureus dengan zona hambat masing masing 19,23 mm dan 18,30 mm. Konsentrasi hambat minimum enzim bromelin dari kulit dan bonggol Nanas adalah 1% dengan zona hambat masing-masing 11,45 mm dan 12,24 mm. Enzim bromelin dari kulit dan bonggol Nanas memberikan aktivitas yang sama dalam menghambat pertumbuhan bakteri Staphylococcus aureus. Kata kunci : Bromelin; Kosentrasi Hambat Minumum; Presipitasi Amonium Sulfat. ABSTRACT The Bromelains are proteolytic enzymes that have the ability to hydrolyze proteins so they can act as antibacterial. Bromelain enzymes can be isolated from the peel, fruit, and stem of pineapple (Ananas comosus (L.) Merr). The purpose of this study was to obtain the concentration of bromelain enzymes from the peel and stem of Pineapple in inhibiting the growth of Staphylococcus aureus. Bromelain was isolated by extraction with phosphate buffer, purified with 60% of ammonium sulfate. Antibacterial activity tests of bromelain enzymes from the peel and stem of pineapple against Staphylococcus aureus were carried out in vitro using disc diffusion by measuring clear zones. The bromelain enzyme concentration used was 1%, 2%, 3% and 4% with chloramphenicol antibiotics as a positive control. The results showed that bromelain enzymes from peel and stem of pineapple at 4% concentration inhibited the growth of Staphylococcus aureus with inhibition zones of 19.23 mm and 18.30 mm respectively. The minimum inhibitory concentration of bromelain enzymes from peel and stem of pineapple was 1% with inhibition zones of 11.45 mm and 12.24 mm respectively. Bromelain enzymes from the peel and stem of pineapple provide the same activity in inhibiting the growth of Staphylococcus aureus bacteria. Keywords : Bromelain; minimum inhibition concentration; ammonium sulfate precipitation
... Bromelain, derived from pineapple [Ananas comosus (L.) Merr.], a Bromeliaceae specie, is a crude preparation known for containing at least four well-studied peptidases: stem bromelain, fruit bromelain, comosain, and ananain (Tochi et al., 2008;Arshad et al., 2014). This enzyme mixture finds diverse applications, including its use in food tenderization, beverages, baking, cosmetic products, preparation of protein hydrolysates, animal feed, tooth whitening, and various sectors of the textile and pharmaceutical industries (Arshad et al., 2014;Manzoor et al., 2016). ...
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The aim of this work was to evaluate the biological activity of protein isolates from the native Bromelia serra (BS) and cultivated bromeliad Ananas comosus (AC) on phytopathogenic microorganisms. Samples of AC were obtained from the experimental station of the Universidad Nacional del Nordeste in Corrientes, Argentina and of BS from natural forests also in Corrientes, Argentina. Extracts of stem and leaves of AC and leaves of BS were processed through a precipitation with acetone, the pellet was re-suspended in autoclaved buffers and called protein isolates. The antimicrobial activity was evaluated by the disc diffusion technique, using phytopathogenic bacteria. However, an inhibition zone was not observed in any of the treatments with protein isolates, unlike the positive control with Streptomycin. The minimum inhibitory concentration of bacterial growth was determined by broth microdilution technique. The results showed that the protein isolates did not inhibit bacterial growth. Furthermore, antifungal activity against Fusarium oxysporum was evaluated by MTT method, but no significant inhibition was observed either. Although the protein extracts did not show biological activity against the microorganisms evaluated, future experiments will continue the evaluation by using other microorganisms. In addition, after a purification scheme will be established, different operational conditions and tests will be used with pure enzymes instead of their extracts.
... Another absorbing nutraceutical agent is Bromelain. Much evidence in vitro and in vivo indicates the possible use of Bromelain in the therapeutic field [11,12]. Studies show that the use of supplements in combination with Bromelain, due to its neuroprotective, anti-inflammatory, and antioxidant role, including the ability to protect against hypoxia and angiogenesis, allows protection in the management of retinopathies such as DR and DME [13,14]. ...
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Diabetic macular edema (DME) represents the most common cause of sight loss in diabetic patients. It is characterized by swelling and thickening of the macula due to sub-and intra-retinal fluid accumulation in the macula, triggered by the breakdown of the inner blood-retinal barrier due to vessel glycosylation and inflammation. Therefore, antioxidant agents like nu-traceuticals as adjuvant or prophylactic tools to standard therapies can become another weapon in the therapy of DME. Cur-cumin and Bromelain have shown in vitro and in vivo antioxidant, anti-inflammatory, and antiproliferative activity. This study aimed to explore the effectiveness of curcumin-based drugs in oral administration followed by SMLP in diabetic patients with clinically significant DME. Methods: We enrolled 24 eyes, both naïve or not naïve, patients, older than 50 years old, with clinically significant DME and a central macular thickness (CMT) of 350 um or more measured by optical coherence tomography with a minimum follow up of 6 months. Fifteen patients were assigned to subthreshold micropulse laser photocoagulation (SMLP); the other nine patients were assigned to subthreshold micropulse laser photocoagulation associated with oral administration of a cur-cumin-based drug. Results: at the 4-month follow-up, the group of patients treated with sub-threshold micropulse laser associated with curcu-2 JScholar Publishers J Ophthalmol Open Access 2024 | Vol 8: 102 min-based drug showed a lower mean CMT at OCT, compared to the group treated with laser alone. We found the same at the 6-month follow-up, with statistical significance. Conclusions: Our study found no retreatment was necessary for patients who underwent SMLP and oral curcumin-based therapy. These patients experienced a significant decrease in CMT, confirmed at the OCT fovea B-scan at 4 and 6 months. Patients who underwent SMLP alone instead were found to have developed an increase in CMT, and retreatments were performed .
... These molecules play crucial roles in leukocyte trafficking, cellular adhesion, and the induction of pro-inflammatory mediators, and they exert immunomodulatory effects on T cells. Bromelain also regulates proinflammatory prostaglandins by inhibiting thromboxane A2 and prostaglandin E. Additionally, it modulates p-selectin-mediated neutrophil recruitment [25] and regulates the blood levels of bradykinin and also plasma fibrinogen [26]. These mechanisms make bromelain potentially effective against various conditions associated with inflammation. ...
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Citation: Colletti, A.; Procchio, C.; Pisano, M.; Martelli, A.; Pellizzato, M.; Cravotto, G. An Evaluation of the Effects of Pineapple-Extract and Bromelain-Based Treatment after Mandibular Third Molar Surgery: A Randomized Three-Arm Clinical Study. Nutrients 2024, 16, 784. Abstract: A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf ®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf ® , purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study's conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf ® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery.
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A three-arm, randomized, placebo controlled clinical study has been performed to evaluate the effects of a lyophilized pineapple extract titrated in bromelain (Brome-Inf®), and purified bro-melain on pain, swelling, trismus and quality of life (QoL) after the surgical removal of the lower third molars. Moreover, the need for non-steroidal anti-inflammatory drugs (NSAIDs) has also been evaluated and compared with a placebo group. The study included 42 people that required the extraction of a single mandibular third molar under local anesthesia. The patients were ran-domized and distributed to receive Brome-Inf®, purified bromelain or placebo and started the treatment the day of surgery and continued it for the next 7 days. The primary outcome was the requirement of NSAIDs in the three groups. The outcome variables were pain, swelling and trismus, which were measured postoperatively at 1, 3, and 7 days. The differences in the efficacy of the freeze-dried pineapple extract and single-component bromelain were also evaluated. At the end of the study, the assumption of ibuprofen (from days 1-7) was statistically higher in the placebo group (p
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