Research on Bromelain
Nutritional support for wound healing.
Altern Med Rev. 2003 Nov;8(4):359-77.
MacKay D, Miller AL.
Thorne Research, Inc., PO Box 25, Dover, ID 83825, USA. email@example.com
Healing of wounds, whether from accidental injury or surgical intervention,
involves the activity of an intricate network of blood cells, tissue types,
cytokines, and growth factors. This results in increased cellular activity,
which causes an intensified metabolic demand for nutrients. Nutritional deficiencies
can impede wound healing, and several nutritional factors required for wound
repair may improve healing time and wound outcome. Vitamin A is required for
epithelial and bone formation, cellular differentiation, and immune function.
Vitamin C is necessary for collagen formation, proper immune function, and as
a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the
skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain
reduces edema, bruising, pain, and healing time following trauma and surgical
procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic
acid production in the wound. Adequate dietary protein is absolutely essential
for proper wound healing, and tissue levels of the amino acids arginine and
glutamine may influence wound repair and immune function. The botanical medicines
Centella asiatica and Aloe vera have been used for decades, both topically and
internally, to enhance wound repair, and scientific studies are now beginning
to validate efficacy and explore mechanisms of action for these botanicals.
To promote wound healing in the shortest time possible, with minimal pain, discomfort,
and scarring to the patient, it is important to explore nutritional and botanical
influences on wound outcome.
PMID: 14653765 [PubMed - in process]
Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent
fashion in an open study of otherwise healthy adults.
Phytomedicine. 2002 Dec;9(8):681-6.
Walker AF, Bundy R, Hicks SM, Middleton RW.
Hugh Sinclair Unit of Human Nutrition, The University of Reading, UK. firstname.lastname@example.org
There is preliminary clinical evidence to support the contention that the anti-inflammatory
and analgesic properties of bromelain help to reduce symptoms of osteo- and
rheumatoid arthritis. However, there have been no controlled studies of its
effects on joint health in healthy subjects who lack such diagnosis. The current
study investigated the effects of bromelain on mild acute knee pain of less
than 3 months duration in otherwise healthy adults. The study was an open, dose-ranging
postal study in volunteers who had been recruited through newspaper and magazine
articles. Two validated questionnaires (WOMAC knee health Index and the Psychological
Well-Being Index) were completed at baseline and after one month's intervention
with bromelain, randomly allocated to volunteers as either 200 mg or 400 mg
per day. Seventy seven subjects completed the study. In both treatment groups,
all WOMAC symptom dimension scores were significantly reduced compared with
baseline, with reductions in the final battery (total symptom score) of 41 and
59% (P = 0.0001 and <0.0001) in the low and high dose groups respectively.
In addition, improvements in total symptom score (P = 0.036) and the stiffness
(P = 0.026) and physical function (P = 0.021) dimensions were significantly
greater in the high-dose (400 mg per day) compared with the low-dose group.
Compared to baseline, overall psychological well-being was significantly improved
in both groups after treatment (P = 0.015 and P = 0.0003 in the low and high
dose groups respectively), and again, a significant dose-response relationship
was observed. We conclude that bromelain may be effective in ameliorating physical
symptoms and improving general well-being in otherwise healthy adults suffering
from mild knee pain in a dose-dependant manner. Double blind, placebo-controlled
studies are now warranted to confirm these results.
- Clinical Trial
- Randomized Controlled Trial
PMID: 12587686 [PubMed - indexed for MEDLINE]
Nutritional and botanical modulation of the inflammatory cascade--eicosanoids,
cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy.
Integr Cancer Ther. 2002 Mar;1(1):7-37; discussion 37.
Nutritional Solutions, Inc., 2935 North, 1000 East, North Logan, UT 84341,
Emerging on the horizon in cancer therapy is an expansion of the scope of treatment
beyond cytotoxic approaches to include molecular management of cancer physiopathology.
The goal in these integrative approaches, which extends beyond eradicating the
affected cells, is to control the cancer phenotype. One key new approach appears
to be modulation of the inflammatory cascade, as research is expanding that
links cancer initiation, promotion, progression, angiogenesis, and metastasis
to inflammatory events. This article presents a literature review of the emerging
relationship between neoplasia and inflammatory eicosanoids (PGE2 and related
prostaglandins), with a focus on how inhibition of their synthesizing oxidases,
particularly cyclooxygenase (COX), offers anticancer actions in vitro and in
vivo. Although a majority of this research emphasizes the pharmaceutical applications
of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors, these
agents fail to address alternate pathways available for the synthesis of proinflammatory
eicosanoids. Evidence is presented that suggests the inhibition of lipoxygenase
and its by-products-LTB4, 5-HETE, and 12-HETE-represents an overlooked but crucial
component in complementary cancer therapies. Based on the hypothesis that natural
agents capable of modulating both lipoxygenase and COX may advance the efficacy
of cancer therapy, an overview and discussion is presented of dietary modifications
and selected nutritional and botanical agents (notably, omega-3 fatty acids,
antioxidants, boswellia, bromelain, curcumin, and quercetin) that favorably
influence eicosanoid production.
PMID: 14664746 [PubMed - in process]
Respiratory and allergic diseases: from upper respiratory tract infections to
Prim Care. 2002 Jun;29(2):231-61.
Division of Wellness and Chronic Illness, Department of Family Medicine, University
Hospital and Medical Center, Health Sciences Center, State University of New
York at Stony Brook, Stony Brook, NY 11794-8461, USA. email@example.com
Patients with asthma and allergic rhinitis may benefit from hydration and a
diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3
fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds), onions,
and fruits and vegetables (at least five servings a day). Physicians may need
to be more cautious when prescribing antibiotics to children in their first
year of life when they are born to families with a history of atopy. More research
is needed to establish whether supplementation with probiotics (lactobacillus
and bifidobacterium) during the first year of life or after antibiotic use decreases
the risk of developing asthma and allergic rhinitis. Despite a theoretic basis
for the use of vitamin C supplements in asthmatic patients, the evidence is
still equivocal, and long-term studies are needed. The evidence is stronger
for exercise-induced asthma, in which the use of vitamin C supplementation at
a dosage of 1 to 2 g per day may be helpful. It is also possible that fish oil
supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day,
also may be helpful to some patients with asthma. Long-term studies of fish
oil and vitamin C are needed for more definite answers. For the patient interested
in incorporating nutritional approaches, vitamin C and fish oils have a safe
profile. However, aspirin-sensitive individuals should avoid fish oils, and
red blood cell magnesium levels may help in making the decision whether to use
additional magnesium supplements. Combination herbal formulas should be used
in the treatment of asthma with medical supervision and in collaboration with
an experienced herbalist or practitioner of TCM. Safe herbs, such as Boswellia
and gingko, may be used singly as adjuncts to a comprehensive plan of care if
the patient and practitioner have an interest in trying them while staying alert
for drug-herb interactions. No data on the long-term use of these single herbs
in asthma exist. For the motivated patient, mind-body interventions such as
yoga, hypnosis, and biofeedback-assisted relaxation and breathing exercises
are beneficial for stress reduction in general and may be helpful in further
controlling asthma. Encouraging parents to learn how to massage their asthmatic
children may appeal to some parents and provide benefits for parents and children
alike. Acupuncture and chiropractic treatment cannot be recommended at this
time, although some patients may derive benefit because of the placebo effect.
For patients with allergic rhinitis, there are no good clinical research data
on the use of quercetin and vitamin C. Similarly, freeze-dried stinging nettle
leaves may be tried, but the applicable research evidence also is poor. Further
studies are needed to assess the efficacy of these supplements and herbs. Homeopathic
remedies based on extreme dilutions of the allergen may be beneficial in allergic
rhinitis but require collaboration with an experienced homeopath. There are
no research data on constitutional homeopathic approaches to asthma and allergic
rhinitis. Patients with COPD are helped by exercise, pulmonary rehabilitation,
and increased caloric protein and fat intake. Vitamin C and n-3 supplements
are safe and reasonable; however, studies are needed to establish their efficacy
in COPD. On the other hand, there are convincing data in favor of N-acetyl-cysteine
supplementation for the patient with COPD at doses ranging between 400 and 1200
mg daily. Red blood cell magnesium levels may guide the use of magnesium replacement.
The use of L-carnitine and coenzyme Q10 in patients with COPD needs further
study. The addition of essential oils to the dietary regimen of patients with
chronic bronchitis is worth exploring. Patients with upper respiratory tract
infections can expect a shorter duration of symptoms by taking high doses of
vitamin C (2 g) with zinc supplements, preferably the nasal zinc gel, at the
onset of their symptoms. Adding an herb such as echinacea or Andrographis shortens
the duration of the common cold. The one study on Elderberry's use for the flu
was encouraging, and the data on the homeopathic remedy Oscillococcinum interesting,
but more studies should be performed. Saline washes may be helpful to patients
with allergic rhinitis and chronic sinusitis. Patients also may try the German
combination (available in the United States) of elderberry, vervain, gentian,
primrose, and sorrel that has been tested in randomized clinical trials. Bromelain
is safe to try; the trials of bromelain supplementation were promising but were
never repeated. The preceding suggestions need to be grounded in a program based
on optimal medical management. Patients need to be well educated in the proper
medical management of their disease and skilled at monitoring disease stability
and progress. Asthmatic patients need to monitor their bronchodilator usage
and peak flow meter measurements to step up their medical treatment in a timely
manner, if needed. Patients welcome physician guidance when exploring the breadth
of treatments available today. A true patient-physician partnership is always
empowering to patients who are serious about regaining their function and health.
PMID: 12391710 [PubMed - indexed for MEDLINE]
Administration of proteolytic enzymes bromelain and trypsin diminish the number
of CD4+ cells and the interferon-gamma response in Peyer's patches and spleen
in endotoxemic balb/c mice.
Cell Immunol. 2002 Feb;215(2):113-9.
Manhart N, Akomeah R, Bergmeister H, Spittler A, Ploner
M, Roth E.
Department of Surgical Research, University Vienna, Austria. firstname.lastname@example.org
Recent publications revealed that bromelain exerts a marked effect on T-cell
response by inhibiting T-cell signal transduction. These experimental studies
may help to explain former clinical investigations showing that Phlogenzym (PHL),
a preparation consisting of the proteases bromelain and trypsin and the antioxidant
rutosid, ameliorate certain diseases with an underlying inflammatory process.
In this study, we showed that orally administered PHL significantly reduced
lymphocyte subpopulations in Peyer's patches (PPs) of healthy and endotoxemic
mice. Similarly, the number of splenic lymphocytes in endotoxin-boostered mice
was significantly lowered by PHL. The effect of PHL was more pronounced on T
cells than on B cells leading especially to a diminution of CD4+ cells. Moreover,
PHL pretreatment decreased IFN-gamma mRNA in PPs and spleen of endotoxemic mice.
These results reveal that PHL may ameliorate inflammatory process by reducing
the number of CD4+ cells and by diminishing INF-gamma mRNA levels.
PMID: 12202148 [PubMed - indexed for MEDLINE]
Effects of sources of protein and enzyme supplementation on protein digestibility
and chyme characteristics in broilers.
Br Poult Sci. 2002 Jul;43(3):424-31.
Yu B, Lee TT, Chiou PW.
Department of Animal Science, National Chung-Hsing University, 250 Kuo-Kuang
Road, Taichung 402, Taiwan.
1. The purpose of this study was to evaluate the effects of protein source
and enzyme supplementation on protein digestibility and chyme characteristics
in broilers. 2. One hundred and twenty growing (13 d old) and 60 finishing (34
d old) Arbor Acre strain commercial male broilers were selected and placed into
individual metabolic cages. 3. The experiment was a 5 x 2 factorial arrangement
with 5 different sources of protein: casein, fish meal, soybean meal (SBM),
soy protein concentrate (SPC), maize gluten meal (MGM) and two levels of protease
(bromelain), 0 and 65 CDU/kg diets. 4. The diets were iso-nitrogenous and semi-purified,
with Cr2O3 as an indicator for determination of ileal digestibility and chyme
characteristics. 5. Apparent ileal protein digestibility (AIPD) in both growing
and finishing chickens was highest on the casein diet, followed by fish meal,
SBM, SPC and MGM. 6. Enzyme inclusion did not improve protein digestibility,
but significantly decreased the digesta pH value in the gizzard and increased
pH in the ileum in the 3-week-old broilers. 7. The digesta pH values in the
gizzard and duodenum were significantly lower in the SBM and fish meal groups
compared with the other protein groups. The molecular weight distribution pattern
of the soluble protein in the chyme of the gastrointestinal (GI) segments showed
a similar trend, regardless of the enzyme inclusion or the stage of growth.
8. The molecular weight profile of soluble protein changed dynamically in the
casein fed broilers from the gizzard to ileum and the low molecular weight proteins,
< 7 kDa, reached maximum levels at the ileum. The molecular weight profile
of the soluble protein in the SBM and SPC changed between the jejunum and the
ileum and in the intermediate molecular soluble protein weight (7 to 10 kDa)
was significantly decreased. This indicated that the hydrolysis process began
from the middle to the posterior end of the small intestine. 9. Similar profiles
were also shown with fish meal protein. The pattern of distribution, however,
did not show any prominent change in the GI segments of the MGM group. 10. The
pepsin, trypsin and chymotrypsin protease activity in the gizzard and duodenum
were highest in the casein group and lowest in the MGM group as compared with
the other protein groups. 11. The rate change in the patterns of molecular weight
distribution in soluble protein and the digestive enzyme activity provide indications
of the partial digestibility of different protein sources. The exogenous enzyme,
bromelain, did not show any beneficial effect on protein digestion.
PMID: 12195802 [PubMed - indexed for MEDLINE]
Efficacy and tolerability of oral enzyme therapy as compared to diclofenac
in active osteoarthrosis of knee joint: an open randomized controlled clinical
J Assoc Physicians India. 2001 Jun;49:617-21.
Tilwe GH, Beria S, Turakhia NH, Daftary GV, Schiess
Department of Medicine, GS Medical College and KEM Hospital, Mumbai.
OBJECTIVE: To compare the efficacy and tolerability of an oral enzyme preparation
(Phlogenzym) with that of an NSAID (diclofenac) in the treatment of active osteoarthrosis.
METHODS: Prospective, randomized, controlled, single-blind study of seven weeks
duration at a tertiary care centre wherein 50 patients aged 40-75 years, with
activated osteoarthrosis of knee joint were randomized to receive phlogenzym
tablets (2-3 tablets, bid) or diclofenac sodium 50 mg bid for three weeks. RESULTS:
At the end of therapy (three weeks) and at follow-up visit at seven weeks there
was reduction in pain and joint tenderness and swelling in both groups, and
slight improvement in the range of movement in the study group. The reduction
in joint tenderness was greater (p < 0.05) in the study group receiving phlogenzym.
CONCLUSION: Phlogenzym is as efficacious and well tolerated as diclofenac sodium
in the management of active osteoarthrosis over three weeks of treatment.
- Clinical Trial
- Randomized Controlled Trial
PMID: 11584936 [PubMed - indexed for MEDLINE]
Preliminary comparison of bromelain and Ibuprofen for delayed onset muscle
Clin J Sport Med. 2002 Nov;12(6):373-8.
Stone MB, Merrick MA, Ingersoll CD, Edwards JE.
Indiana State University, Terre Haute 47809, USA. email@example.com
OBJECTIVE: The purpose of this study was to determine whether a common bromelain
regimen or common ibuprofen regimen are effective in resolving pain and muscle
dysfunction associated with delayed onset muscle soreness of the elbow flexors.
DESIGN: A randomized, double-blinded, repeated measures design was used for
this study. SETTING: The study was performed in the Sports Injury Research Lab
at an NCAA Division I university. PARTICIPANTS: Forty subjects who had not participated
in an upper body resistance-training program 3 months prior to the study, suffered
pain or injury in the nondominant arm, or experienced an adverse response to
nonsteroidal anti-inflammatory drugs or pineapple (bromelain source) were recruited.
Thirty-nine subjects finished the study. INTERVENTIONS: Active range of motion
(ROM), perceived pain, and peak concentric torque measurements of the nondominant
arm were taken prior to and 24, 48, 72, and 96 hours following an eccentric
exercise protocol of the elbow flexors. Subjects were assigned to one of four
treatment groups (bromelain 300 mg t.i.d., ibuprofen 400 mg t.i.d., placebo
t.i.d., and control) and began treatment immediately following the exercise
protocol. MAIN OUTCOME MEASURES: No differences among treatments were observed
for any of the dependent variables at any time. ROM deficits and pain peaked
between 48 and 72 hours. Peak torque deficiencies were observed between 24 and
72 hours. CONCLUSIONS: Ingestion of bromelain and ibuprofen had no effect on
elbow flexor pain, loss of ROM, or loss of concentric peak torque as a result
of an eccentric exercise regimen.
- Clinical Trial
- Randomized Controlled Trial
PMID: 12466693 [PubMed - indexed for MEDLINE]
Bromelain treatment alters leukocyte expression of cell surface molecules involved
in cellular adhesion and activation.
Clin Immunol. 2002 Aug;104(2):183-90.
Hale LP, Greer PK, Sempowski GD.
Department of Pathology, Duke University, Durham, NC 27710, USA.
Bromelain is a natural proteinase preparation derived from pineapple stem that
is marketed for oral use as a digestive aid and as an antiinflammatory agent.
Bromelain treatment in vitro has been previously shown to selectively remove
certain cell surface molecules that may affect lymphocyte migration and activation.
This study reports the effects of bromelain on a broad range of cell surface
molecules and on lymphocytes, monocytes, and granulocytes under physiologically
relevant conditions. In vitro bromelain treatment of leukocytes in whole blood
proteolytically altered 14 of 59 leukocyte markers studied. Constitutively expressed
bromelain-sensitive molecules included CD7, CD8alpha, CD14, CD16, CD21, CD41,
CD42a, CD44, CD45RA, CD48, CD57, CD62L, CD128a, and CD128b. The proteolytic
effect of bromelain increased as the concentration of plasma decreased, with
EC50 ranging from >1000 microg/ml for 100% plasma to approximately 1 microg/ml
in the absence of plasma, indicating the presence of an inhibitor of bromelain
in plasma. alpha2-macroglobulin purified from plasma mimicked the inhibitory
effect of whole plasma on bromelain activity. If proteolysis is required for
the antiinflammatory actions of oral bromelain, these data suggest that the
required concentrations are more likely to be achieved locally in the gastrointestinal
tract or in other tissue sites where the plasma concentration is low, rather
than in the bloodstream. The cell surface molecules altered by bromelain are
involved in leukocyte homing and cellular adhesion and activation. Thus bromelain
could potentially exert an antiinflammatory effect by multiple mechanisms, including
alterations in leukocyte migration and activation.
PMID: 12165279 [PubMed - indexed for MEDLINE]
In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in
the inflammatory exudate in rats.
Pharmacology. 2002 May;65(2):83-6.
Gaspani L, Limiroli E, Ferrario P, Bianchi M.
Department of Pharmacology, University of Milan, Italy.
The effects of bromelain were examined in rats with subcutaneous carrageenin-induced
inflammation. After oral in vivo administration, bromelain (10 and 20 mg/kg
p.o.) induced a significant decrease of both PGE(2) and substance P concentrations
in the exudate. When added to the inflammatory exudate in vitro, the drug (25,
50, 100 microg/ml) did not affect PGE(2) concentrations and induced an increase
in the substance P levels. Our data indicate that bromelain reduces the production
of two key mediators of inflammation. This effect does not seem to be related
to a direct action of the drug on PGE(2) and SP released in the exudate in response
to the inflammatory stimulus. Copyright 2002 S. Karger AG, Basel
PMID: 11937778 [PubMed - indexed for MEDLINE]
Bromelain: biochemistry, pharmacology and medical use.
Cell Mol Life Sci. 2001 Aug;58(9):1234-45.
Department of Biochemistry, Molecular Biology and Biotechnology, Institute
of Pharmacy, Freie Universitat Berlin, Germany. firstname.lastname@example.org
Bromelain is a crude extract from the pineapple that contains, among other
components, various closely related proteinases, demonstrating, in vitro and
in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities.
The active factors involved are biochemically characterized only in part. Due
to its efficacy after oral administration, its safety and lack of undesired
side effects, bromelain has earned growing acceptance and compliance among patients
as a phytotherapeutical drug. A wide range of therapeutic benefits has been
claimed for bromelain, such as reversible inhibition of platelet aggregation,
angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis,
pyelonephritis and enhanced absorption of drugs, particularly of antibiotics.
Biochemical experiments indicate that these pharmacological properties depend
on the proteolytic activity only partly, suggesting the presence of nonprotein
factors in bromelain. Recent results from preclinical and pharmacological studies
recommend bromelain as an orally given drug for complementary tumor therapy:
bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity
of monocytes against tumor cells from patients and by inducing the production
of distinct cytokines such as tumor necrosis factor-a, interleukin (Il)-1beta,
Il-6, and Il-8. In a recent clinical study with mammary tumor patients, these
findings could be partially confirmed. Especially promising are reports on animal
experiments claiming an antimetastatic efficacy and inhibition of metastasis-associated
platelet aggregation as well as inhibition of growth and invasiveness of tumor
cells. Apparently, the antiinvasive activity does not depend on the proteolytic
activity. This is also true for bromelain effects on the modulation of immune
functions, its potential to eliminate burn debris and to accelerate wound healing.
Whether bromelain will gain wide acceptance as a drug that inhibits platelet
aggregation, is antimetastatic and facilitates skin debridement, among other
indications, will be determined by further clinical trials. The claim that bromelain
cannot be effective after oral administration is definitely refuted at this
PMID: 11577981 [PubMed - indexed for MEDLINE]
Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in
Cancer Chemother Pharmacol. 2001 Jul;47 Suppl:S10-5.
Desser L, Holomanova D, Zavadova E, Pavelka K, Mohr
T, Herbacek I.
Institute of Cancer Research, University of Vienna, Austria. email@example.com
Therapy with oral proteolytic enzymes (OET) with combination drug products
containing papain, bromelain, trypsin, and chymotrypsin has been shown to be
beneficial in clinical settings such as radiotherapy-induced fibrosis, bleomycin
pneumotoxicity and immunosuppression in cancer, all of which are nowadays known
to be accompanied by excessive transforming growth factor-beta (TGF-beta) production.
It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in
serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) from
the "slow" form into the "fast" form, whereby the "fast"
form binds and inactivates TGF-beta irreversibly. In this study we have investigated
the effect of OET on the concentration of TGF-beta1 in serum of patients with
rheumatoid arthritis (RA) (n = 38), osteomyelofibrosis (OMF) (n = 7) and herpes
zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta1
levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA).
We have demonstrated that in healthy volunteers and in patients there exists
a correlation between active and latent TGF-beta1 in serum (r=0.8021; P<0.0001).
Treatment with OET had no significant effect on TGF-beta1 concentration in healthy
volunteers or patients with a normal level of TGF-beta1. In patients with elevated
TGF-beta1 concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P
< 0.005), in OMF (P < 0.05) and in HZ (P < 0.05). Conclusion: These
results support the concept that OET is beneficial in diseases characterized
in part by TGF-beta1 overproduction.
PMID: 11561866 [PubMed - indexed for MEDLINE]
Therapy with proteolytic enzymes in rheumatic disorders.
Leipner J, Iten F, Saller R.
Department of Natural Medicine, University Hospital, Zurich, Switzerland.
Plant extracts with a high content of proteolytic enzymes have been used in
traditional medicine for a long time. Besides herbal proteinases, 'modern' enzyme
therapy includes pancreatic enzymes. The therapeutic use of proteolytic enzymes
is empirically based, but is also supported by scientific studies. This review
provides an overview of preclinical and clinical trials of systemic enzyme therapy
in rheumatic disorders. Studies of the use of proteolytic enzymes in rheumatic
disorders have mostly been carried out on enzyme preparations consisting of
combinations of bromelain, papain, trypsin and chymotrypsin. The precise mechanism
of action of systemic enzyme therapy remains unresolved. The ratio of proteinases
to antiproteinases, which is affected by rheumatic diseases, appears to be influenced
by the oral administration of proteolytic enzymes, probably via induction of
the synthesis of antiproteinases or a signal transduction of the proteinase-antiproteinase
complex via specific receptors. Furthermore, there are numerous alterations
of cytokine composition during therapy with orally administered enzymes resulting
from immunomodulatory effects, which might be an indication of the efficacy
of enzyme therapy. The results of various studies (placebo-controlled and comparisons
with nonsteroidal anti-inflammatory drugs) in patients with rheumatic diseases
suggest that oral therapy with proteolytic enzymes produces certain analgesic
and anti-inflammatory effects. However, the results are often inconsistent.
Nevertheless, in the light of preclinical and experimental data as well as therapeutic
experience, the application of enzyme therapy seems plausible in carefully chosen
patients with rheumatic disorders.
PMID: 11784210 [PubMed - indexed for MEDLINE]
[Systemic enzyme therapy in the treatment and prevention of post-traumatic and
Acta Chir Orthop Traumatol Cech. 2001;68(1):45-9.
Kamenicek V, Holan P, Franek P.
Chirurgicke oddeleni nemocnice, Bilovec.
PURPOSE OF THE STUDY: The authors concentrate on the use of enzyme therapy
in traumatology. They monitored SET efficiency in the treatment and prophylazis
of swelling in the postoperative period after the internal fixation of fractures
of long bones and compared it with the effect of standard antiswelling seu antioedematous
drugs on the basis of aescin. MATERIAL: A group of 60 patients was followed
after the fixation of long bones. The average age was 42 years (range, 12-79
years). Fractures were treated by intrameduilary fixation or by external fixators.
The patients were split into two groups. In 30 patients only Phlogenzym was
administered for the treatment and prevention of posttraumatic and postoperative
swelling. Another 30 patients--the control group--were treated by standard antioedematic
drugs on the basis of aescin. The same analgesics were applied in both groups.
METHODS: The group of patients with systemic enzyme therapy were treated by
Phlogenzym in the dosage 3 times 3 tablets in the first three days after operation
and subsequently 3 times 2 tablets in the remaining follow-up period. In the
postoperative period the changes of operated limb volume was monitored. The
circumference of a limb was measured in the area of the largest oedema and 10
cm distally. Then the volume of this part of limb was calculated as the volume
of conical frustum. The measurements were performed on postoperative days 1,
3, 5, 7, 10 and 14. The volume value of the 1st day was used as starting value
(100%). The values of subsequent measurements were then compared to this starting
value in both group of patients. Evaluation of the resorption of traumatic and
postoperative haematoma and analgesis effect of Phlogenzym was also made. RESULTS:
In the group of patients who were administered with Phlogenzym after operation
the reduction of the posttraumatic and postoperative swelling was continuous
and significantly faster in compared with patients of the control group. A remarkable
difference was revealed by the measurement on 5th postoperative day--in patients
treated by Phlogenzym the starting value of the volume of the operated in limb
was reduced on average by almost 8%. In contrast, in the control group treated
by standard drugs this value slightly increased above 100%. At the end of the
first postoperative week the monitored volume was on average reduced by 12%
in the SET group compared with 1.45% in the control group. At the end of the
follow-up--on 14th postoperative day the volume was reduced in the SET group
by almost 17% compared with 9% in the control group. There was also an evidently
good analgesic effect of the drug. The total consumption of analgesics of patients
in the SET group was significantly lower, particularly in the early postoperative
period. In the course of the follow-up of both groups no marked differences
were recorded in the changes of the volume of operated limbs in dependence on
the method of fixation applied (intramedullary or external), sex of the patient
or on the affected limb (lower or upper). The patients tolerated Phlogenzym
very well, only one female patient suffered temporarily from poor digestion
which, however, did not require to interrupt the administration of the drug.
No other undesirable effects occurred. DISCUSSION: Fixation of long bones belongs
to the most frequent operations in traumatological and orthopaedic departments
of all levels. One of the factors which may have an unfavourable effect on the
final result of fixation is a prolonged post-trauma or postoperative swelling.
The results of the study prove a clearly positive effect of system enzymotherapy
on the reduction of oedema accompanying the trauma and inflammation. The study
proved a statistical significance of the acceleration of the reduction of oedema
in patients treated by Phlogenzym as compared to the control group treated by
a standard antioedematous drugs. CONCLUSION: The authors verified that systemic
enzyme therapy could influence significantly the results of traumatological
surgery. Simple administration per os, efficient oedema reduction and thus accelerated
healing, antiophlogistic and analgesic effect--all these advantages justify
the application of this therapeutic method what can be recommended as a part
of the complex treatment in traumatology with both conservative and surgical
- Clinical Trial
- Controlled Clinical Trial
PMID: 11706714 [PubMed - indexed for MEDLINE]
Bromelain is an accelerator of phagocytosis, respiratory burst and Killing of
Candida albicans by human granulocytes and monocytes.
Eur J Med Res. 2001 May 29;6(5):193-200.
Brakebusch M, Wintergerst U, Petropoulou T, Notheis
G, Husfeld L, Belohradsky BH, Adam D.
Dr. von Haunersches Kinderspital, Abtl. fur antimikrobielle Therapie und Infektionsimmunologie,
Munich, Germany. Myga.Brakebusch@lrz.tum.de
OBJECTIVE: The aim of this study was to examine the influence of immuno modulating
agents like bromelain and trypsin (e.g. Wobenzym on granulocyte and monocyte
functions in healthy volunteers and patients with disorders of the humoral immuno
system X-linked agammaglobulinaemia (XLA) and common variable immuno deficiency
(CVID) and to find out whether the unspecific immunity could be improved by
these enzymes. METHODS: In a whole-blood assay kinetics of phagocytosis, respiratory
burst and killing (PBK) were measured in blood samples incubated with and without
bromelain and trypsin (B/T) using Candida albicans as target organism. The time-reaction
curves were analysed determining their gradient (T1) and their onset (T2) as
well as the half effect time (HET). RESULTS: Phagocytes from patients with XLA
showed a significantly accelerated basal phagocytosis (reduction of HET by 24%
p < 0.001) compared to healthy controls. After incubation with B/T (10 microg/ml
each) speed of phagocytosis was nearly doubled (phagocyte activity p < 0.0001,
Candida uptake p < 0.003), T2 of respiratory burst was reduced by 65 % (p
< 0.0001) and killing was accelerated by 27% (p < 0.046). However, the
maximal activities of all kinetics were not altered. Incubation of phagocytes
from healthy controls with B/T accelerated phagocytosis to a level comparable
to that of untreated phagocytes from patients with XLA and also accelerated
reactive oxygen species (ROS) production (reduction of HET by 28%, p < 0.012).
In contrast to phagocytes from patients with XLA, phagocytes of patients with
CVID showed a similar stimulation by B/T like healthy controls. Further experiments
with the single substances showed that bromelain was the active compound. CONCLUSION:
Our data suggest, that bromelain possesses immuno stimulatory properties. Phagocytes
of XLA patients appear to be particularly susceptible to this stimulation.
PMID: 11410400 [PubMed - indexed for MEDLINE]
Inhibitory effect of enzyme therapy and combination therapy with cyclosporin
A on collagen-induced arthritis.
Clin Exp Rheumatol. 2001 May-Jun;19(3):303-9.
Rovenska E, Svik K, Stancikova M, Rovensky J.
Research Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 01 Piest'any,
Slovak Republic. firstname.lastname@example.org
OBJECTIVE: There is increasing interest in the use of combination therapy for
rheumatoid arthritis and in the possibility of combining the conventional drug
approach with newer antirheumatic therapy. The present study investigates the
efficacy of long-term prophylactic enzyme therapy and combination therapy with
cyclosporin A in rats with collagen-induced arthritis. METHODS: Rats with collagen-induced
arthritis were administered the following drugs: cyclosporin A (5 mg/kg/day
and 10 mg/kg/day orally); a mixture of enzymes containing pure substances (bromelain,
trypsin, rutin) in the same ratio as in Phlogenzym (PHL, 150 mg/kg, twice daily
intrarectally); and a combination of 5 mg/kg/day cyclosporin A plus 300 mg/kg/day
PHL for a period of 50 days from the immunization. Levels of serum albumin,
serum nitrite/nitrate concentrations, changes in hind paw swelling and bone
erosions were measured in the rats as variables of inflammation and destructive
arthritis-associated changes. RESULTS: Treatment with 10 mg/kg cyclosporin A,
as well as combination therapy with half dosages of cyclosporin A (5 mg/kg)
plus PHL significantly inhibited both inflammation and destructive arthritis-associated
changes. Significant differences in favor of combination therapy with 5 mg/kg
CsA + 300 mg/kg PHL as compared to 5 mg/kg CsA alone were seen in hind paw swelling.
Also, reduction of the radiographic scores was more significant in the combination
therapy group. Five mg cyclosporin A or PHL alone reduced the disease markers
studied to a lesser extent, and in the case of enzyme therapy this occurred
at a later stage of arthritis development. CONCLUSION: Our results show the
inhibitory effect of enzyme therapy on collagen-induced arthritis in rats, as
well as the efficacy of cyclosporin A given in low doses in combination with
enzyme therapy, which may be useful in the treatment of rheumatoid arthritis.
PMID: 11407084 [PubMed - indexed for MEDLINE]
Enzyme and combination therapy with cyclosporin A in the rat developing adjuvant
Int J Tissue React. 1999;21(4):105-11.
Rovenska E, Svik K, Stancikova M, Rovensky J.
Research Institute for Rheumatic Diseases, Piest'any, Slovak Republic. email@example.com
Recent knowledge of the pathophysiology of rheumatoid arthritis and the mechanism
of drug effects have enabled the use of new drugs and drug combinations in rheumatoid
arthritis therapy. This study investigates the efficacy of both enzyme therapy
and combined therapy with cyclosporin in rats with adjuvant arthritis. Rats
with adjuvant-induced arthritis were administered either cyclosporin A (2.5
or 5.0 mg/kg/day per os), a mixture of enzymes (Phlogenzym (PHL); 45 mg/kg twice
daily intrarectally), or a combination of 2.5 mg cyclosporin A and 90 mg PHL
for a period of 40 days from the adjuvant application. Levels of serum albumin,
changes in hind paw swelling and bone erosions were measured in rats as variables
of inflammation and arthritis-associated destructive changes. Treatment with
5 mg of cyclosporin A, as well as with the combination therapy with cyclosporin
A plus PHL, significantly inhibited both the inflammation and destructive arthritis-associated
changes. However, 2.5 mg of cyclosporin A and PHL alone inhibited these disease
markers, although to a lesser extent and at a later stage of arthritis development.
The results show the inhibitory effect of enzyme therapy on rat adjuvant arthritis,
as well as the efficacy of a low dose of cyclosporin A given in combination
with enzyme therapy, which may be useful in the treatment of rheumatoid arthritis.
PMID: 10761540 [PubMed - indexed for MEDLINE]
Natural treatment of perennial allergic rhinitis.
Thornhill SM, Kelly AM.
Altern Med Rev. 2000 Oct;5(5):448-54.
Northwestern Health Sciences University College of Chiropractic, Bloomington,
MN 55431, USA.
Perennial allergic rhinitis is an IgE-mediated inflammatory disorder of the
nasal mucosa characterized by paroxysms of sneezing, nasal congestion, pruritis,
and rhinorrhea. The condition may be caused by certain environmental agents,
food sensitivities, structural abnormalities, metabolic conditions, or synthetic
drugs. Recent health impairment outcome studies on allergic rhinitis sufferers
reveal a measurable decline in physical and mental health status and the inability
to perform daily activities. Antihistamines, decongestants, anticholinergic
agents, and corticosteroid drug therapy, alone or in combination, are typically
used in the treatment of allergic rhinitis. Reported adverse side effects include
sedation, impaired learning/memory, and cardiac arrhythmias. Therapeutic strategies
should seek to decrease the morbidity already associated with this condition.
Urtica dioica, bromelain, quercetin, N-acetylcysteine, and vitamin C are safe,
natural therapies that may be used as primary therapy or in conjunction with
PMID: 11056414 [PubMed - indexed for MEDLINE]
Bromelain proteases reduce human platelet aggregation in vitro, adhesion to
bovine endothelial cells and thrombus formation in rat vessels in vivo.
In Vivo. 1999 Jan-Feb;13(1):7-12.
Metzig C, Grabowska E, Eckert K, Rehse K, Maurer HR.
Institute of Pharmacy, Free University of Berlin, Germany.
The thiol protease, bromelain, an extract from pineapple stem, was suggested
to have antithrombotic and anticoagulant activities in vivo. We studied the
effects of bromelain on cell size distribution of isolated human platelets in
vitro by Coulter Counter measurements. Preincubation of platelets with bromelain
(10 micrograms/mL) completely prevented the thrombin (0.2 U/mL) induced platelet
aggregation. Papain was less active in preventing platelet aggregation. In vitro,
bromelain (0.1 microgram/mL) reduced the adhesion of bound, thrombin stimulated,
fluorescent labeled platelets to bovine aorta endothelial cells. In addition,
preincubation of platelets with bromelain, prior to thrombin, activation, reduced
the platelet adhesion to the endothelial cells to the low binding value of unstimulated
platelets. On the basis of mass concentrations, the proteases papain and trypsin
were as effective as bromelain. Using a laser thrombosis model, the in vivo
effects of orally and intraveneously applied bromelain on thrombus formation
in rat mesenteric vessels were studied. Bromelain, orally applied at 60 mg/kg
body weight, inhibited the thrombus formation in a time dependent manner, the
maximum being after 2 hours in 11% of arterioles and 6% of venoles. Intravenous
application at 30 mg/kg was slightly more active in reducing thrombus formation
in arterioles (13%) and venoles (5%), suggesting that orally applied bromelain
is biologically active. These results may help to explain some of the clinical
effects observed after bromelain treatment in patients with thrombosis and related
PMID: 10218125 [PubMed - indexed for MEDLINE]
Effects of oral bromelain administration on the impaired immunocytotoxicity
of mononuclear cells from mammary tumor patients.
Oncol Rep. 1999 Nov-Dec;6(6):1191-9.
Eckert K, Grabowska E, Stange R, Schneider U, Eschmann
K, Maurer HR.
Institut fur Pharmazie der Freien Universitat Berlin, Berlin, Germany.
The protease bromelain from pineapple was suggested for adjuvant therapy of
malignant diseases. We studied immunological effects of an orally applied bromelain
drug on 16 breast cancer patients in comparison with healthy donors. Bromelain
was applied for 10 days with a daily dose of 3000 F.I.P. units and the immunocytotoxicity
of blood monocytes and lymphocytes against the leukemic K562 and MDA-MB-231
mammary carcinoma target cells was determined in vitro. In addition, the expression
of the cell surface markers CD44, CD16, CD11a and CD62L on lymphocytes and the
secretion of IL-2 and IL-1beta from monocytes was measured. Patients leukocytes
expressed lower bMAK-, MAK-, NK- and LAK-cell activities, compared with those
from healthy donors. Orally applied bromelain increased the reduced bMAK- and
MAK-cell activity of patients monocytes about 2-fold. When the patients were
classified on the basis of bromelain effects on the monocytic cytotoxicity into
bromelain responders and nonresponders, about 40% of the patients responded
to bromelain with an increase of cytotoxicity from 7.8% to 54% (bMAK-cell activity)
and from 16% to 47% (MAK-cell activity). Bromelain was less effective on the
higher cytotoxicity of monocytes from healthy donors, but stimulated the secretion
of IL-1beta from monocytes. In contrast, patient monocytes secreted no detectable
IL-1beta, before, during and after bromelain treatment. Bromelain had no effects
on the impaired patients NK- and LAK-cell activity, but reduced the LAK-cell
activity of healthy donors. No IL-2 was found in the supernatants of untreated
and treated lymphocytes from healthy donors. Bromelain reduced the expression
of CD44, but weakly increased CD11a and CD62L expression on patient lymphocytes,
whereas CD16 remained unchanged. In vitro bromelain application to lymphocytes
had similar effects, with greater reduction rates of CD44 and CD16 expression.
As to coagulation parameters in plasma of healthy donors, the activated partial
thromboplastin time was increased from 38 to 46 sec, leaving prothrombin time
and plasminogen unchanged. These data suggest, that orally applied bromelain
stimulates the deficient monocytic cytotoxicity of mammary tumor patients, which
may partially explain its proposed antitumor activity.
PMID: 10523679 [PubMed - indexed for MEDLINE]
[Reducing pain by oral enzyme therapy in rheumatic diseases]
Wien Med Wochenschr. 1999;149(21-22):577-80.
Klein G, Kullich W.
Sonderkrankenanstalt fur rheumatische Erkrankungen und Herz-Kreislaufkrankheiten
der PVArb, Saalfelden.
Proteolytic enzymes have analgesic, effects, besides the wellknown antiinflammatory
and edema-reducing properties. These analgesic effects are based on the inhibition
of inflammation and in addition to that on direct influences on the nociceptors.
All that explains the therapeutical effects of such enzymes in degenerative-rheumatic
and soft tissue rheumatic diseases in which inflammatory or immunologic processes
are not in the forefront. In recent years a significant reduction of pain in
various rheumatic diseases, concerning these aspects, was shown in several clinical
studies. The clinical trial in patients with periarthritis of shoulder showed
statistical equivalence of pain reduction, whether they were treated with phlogenzym
or diclofenac. Likewise in the trial of patients suffering from painful osteoarthritis
of the knee, there was a statistical equivalence of the pain-scores, comparing
diclofenac and enzymes. The study of painful vertebral syndromes again resulted
in equivalence of the treatment with NSAIDs compared to therapy with enzymes.
- Clinical Trial
- Randomized Controlled Trial
- Review, Tutorial
PMID: 10666820 [PubMed - indexed for MEDLINE]
Prevention of murine EAE by oral hydrolytic enzyme treatment.
J Autoimmun. 1999 May;12(3):191-8.
Targoni OS, Tary-Lehmann M, Lehmann PV.
Institute of Pathology, School of Medicine, Case Western Reserve University,
Cleveland, Ohio, 44106, USA.
Clinical trials that test the efficacy of Phlogenzym (consisting of the hydrolytic
enzymes bromelain and trypsin and the anti-oxidant rutosid) as a treatment for
T cell-mediated autoimmune diseases including multiple sclerosis (MS), type
1 diabetes and rheumatoid arthritis are presently ongoing. We tested the effects
of Phlogenzym treatment in the murine model for MS, experimental allergic encephalomyelitis
(EAE), a disease induced in SJL mice by immunization with proteolipid protein
(PLP) peptide 139-151. Oral administration of Phlogenzym resulted in complete
protection from EAE. In Phlogenzym-treated mice, the dose response curve of
the PLP:139-151-specific T cell response was shifted to the right, that is,
the primed T cells required higher peptide concentrations to become activated.
Additionally, the T cell response to this peptide was shifted towards the T
helper 2 cytokine profile. Both effects are consistent with an increased T cell
activation threshold. In support of this interpretation, we found that the accessory
molecules CD4, CD44, and B7-1 (all of which are involved in T cell co-stimulation)
were cleaved by Phlogenzym, while CD3 and MHC class II molecules (which are
involved in the recognition of antigens by T cells) and LFA-1 were unaffected.
These data show the efficacy of oral Phlogenzym treatment in an animal model
of T cell-mediated autoimmune disease and suggest that the protective effect
might be the result of an increase in the activation threshold of the autoreactive
T lymphocytes brought about by the cleavage of accessory molecules involved
in the interaction of T cells and antigen presenting cells. Copyright 1999 Academic
PMID: 10222028 [PubMed - indexed for MEDLINE]
Protein-G binding material from synovial fluid of rheumatoid arthritis patients
induces unorthodox autoantibodies (IgG1 rheumatoid factor) in NZB, NZW and (NZB
x NZW)F1 mice.
Eur J Immunol. 1994 Mar;24(3):684-91.
Abedi-Valugerdi M, Ridderstad A, Lettesjo H, Strom H,
Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm
Our previous studies have demonstrated that injection of rheumatoid arthritis
(RA) synovial fluid (SF) induces a marked increase mainly of IgG1 antibody-producing
cells in autoimmune disease prone (NZB x NZW)F1 mice but not in CBA mice. In
the present study, the in vivo effect of RA-SF on autoantibody production was
tested in different strains of mice. Injection of RA-SF induced the production
of unorthodox autoantibodies (IgG1 rheumatoid factor, RF) in young (NZB x NZW)F1
mice as well as in their parental strains NZB and NZW, but not in normal mice
(CBA) or in mice with severe combined immunodeficiency, indicating that the
response is not caused by a conventional immune response against RA-SF material.
IgG1 RF production was rapidly induced and reached high levels already on day
7 and lasted for more than 90 days. The induction of IgG1 RF was not the result
of polyclonal activation, since RA-SF did not stimulate the production of other
antibodies, such as autoantibodies against double-stranded DNA, bromelain-treated
mouse red blood cells, myosin, transferrin, cytochrome c, thyroglobulin or myoglobin
or antibodies reactive with the hapten TNP. To elucidate the identity of the
active substance in RA-SF, responsible for IgG1 RF production, bound and unbound
material of RA-SF, eluted from a protein-G column was injected into (NZB x NZW)F1
mice. Only the protein-G binding material was active, indicating that the effect
is mediated by autoantibodies or immune complexes in the synovial fluid. Further
studies demonstrated that identical concentrations of protein obtained from
a pool of normal human IgG or SF from seronegative RA and non-RA arthritides
patients did not contain the same activity.
PMID: 8125137 [PubMed - indexed for MEDLINE]
Reactivity of mouse antibodies against bromelain-treated mouse erythrocytes
with thrombin-treated mouse platelets.
Immunology. 1989 Mar;66(3):335-8.
Department of Microbiology and Immunology, Shimane Medical University, Japan.
The reactivity of mouse antibodies against bromelain-treated mouse erythrocytes
(BrMRBC) with mouse platelets before and after thrombin treatment was assessed
by flow cytometry. Anti-BrMRBC antibodies could bind to thrombin-treated platelets,
although normal platelets were also weakly reactive with the antibodies. The
binding of anti-BrMRBC antibodies to platelets was confirmed by complement-dependent
lysis. It is suggested that thrombin-activated platelets may be a real target
for anti-BrMRBC antibodies.
PMID: 2467876 [PubMed - indexed for MEDLINE]
On the pharmacology of bromelain: an update with special regard to animal studies
on dose-dependent effects.
Planta Med. 1990 Jun;56(3):249-53.
Bromelain, a standardized complex of proteases from the pineapple plant, is
absorbed unchanged from the intestine of animals at a rate of 40%; in animal
experiments it was found to have primarily anti-edema, antiinflammatory, and
coagulation-inhibiting effects. These effects are due to an enhancement of the
serum fibrinolytic activity and inhibition of the fibrinogen synthesis, as well
as a direct degradation of fibrin and fibrinogen. Bromelain lowers kininogen
and bradykinin serum and tissue levels and has an influence on prostaglandin
synthesis, thus acting antiinflammatory. In in vitro and in animal studies,
experimentally induced tumours could be inhibited by bromelain. Although many
studies do not give extensive statistical data, the effects of bromelain in
animal studies seem to be dose-dependent. Further investigations have to be
PMID: 2203073 [PubMed - indexed for MEDLINE]
Activation of murine autoreactive b cells by interleukin 1-like factors released
from synovial inflammatory cells of rheumatoid arthritis patients.
Bazzichi L, Soletti AL, Ciompi ML, Garzelli C.
Institute of Medical Pathology, University of Pisa.
The effect of interleukin 1 (IL-1)-like factor(s), produced by cells isolated
from the synovial fluids of rheumatoid arthritis (RA) patients, on an in vitro
murine model of spontaneous autoimmunity, i.e., the development of plaque-forming
cells (PFC) to bromelain-treated mouse red blood cells (Br-MRBC) in mouse peritoneal
cell (PC) cultures, has been investigated. It has been found that IL-1-containing
culture supernatants from cells isolated from joint fluids of RA patients, as
well as recombinant IL-1, determine a marked increase in anti-Br-MRBC PFC development.
Moreover, factor(s) of 10-20 KD molecular weight, with IL-1-like biological
activity, capable of increasing the anti-Br-MRBC PFC development in mouse PC
cultures, have been demonstrated in joint fluids from RA patients. The finding
that synovial inflammatory cells produce factors that activate autoreactive
B cells further supports the role of autoimmunity in the pathogenesis of rheumatoid
arthritis, as self-perpetuing disorder.
PMID: 1932507 [PubMed - indexed for MEDLINE]
Isolation of a fibrinolysis enzyme activator from commercial bromelain.
Arch Int Pharmacodyn Ther. 1981 Nov;254(1):157-67.
Ako H, Cheung AH, Matsuura PK.
A fibrinolysis enzyme activator was isolated from commercial bromelain. This
enzyme preparation is used medicinally. A by-product of bromelain production,
the acetone still residue, was used as a starting material to develop an isolation
scheme which began with reversed phase chromatography, was followed by ion exchange
chromatography, and ended with ultrafiltration. It had polarity and ion exchange
properties similar to those of a neutral amino acid. The active substance has
no intrinsic fibrinolytic activity but appears to enhance the activity of one
of the fibrinolytic enzymes. The presence of the fibrinolysis enzyme activator
in commercial bromelain may explain some of the physiological and clinical effects
observed following the oral administration of the enzyme preparation.
PMID: 7199897 [PubMed - indexed for MEDLINE]
Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis
in heart patients.
Med Hypotheses. 1980 Nov;6(11):1123-33.
It has been established that a bromelain plasminogen activator will produce
plasmin in rat experiments. In addition the plasmin cleaves Hageman factor in
a way that leads to a strong release of kallikrein but a weak release of thrombin.
A possible mechanism is suggested to explain how the body can maintain thrombin
at a level too low to cause platelet aggregation but adequate to stimulate release
of prostaglandins and enzymes for more than 24 hours from a single dose of the
pineapple enzymes. Since bromelain therapy leads to formation of platelets with
increased resistance to aggregation, it is obvious that the dominant endogenous
prostaglandins being produced must be from the group that increases platelet
cyclicAMP levels (prostacyclin, PGE1, etc.). The combination of fibrinolytic
and antithrombic properties appear to be effective and two large scale tests
on heart patients have shown a practically complete elimination of thrombosis.
PMID: 6256612 [PubMed - indexed for MEDLINE]
Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical
application. An update.
J Ethnopharmacol. 1988 Feb-Mar;22(2):191-203.
Taussig SJ, Batkin S.
Department of Food Science and Human Nutrition, School of Tropical Agriculture,