Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bromelain is a mixture of proteinases derived from pineapple stem that is marketed by health food stores as a "digestive aid". A number of studies suggest that bromelain may also have anti-inflammatory activity in vivo, including an anecdotal report describing potential efficacy in inflammatory bowel disease. We and others have previously shown that proteolytically active bromelain removes certain cell surface molecules and affects leukocyte migration, activation, and production of cytokines and inflammatory mediators in vitro. The purpose of this study was to determine whether ingested bromelain retains proteolytic activity within the murine gastrointestinal tract in vivo. The proteolytic activity of bromelain was determined in vitro using model substrates or immunofluorescence assays after administration of various doses and formulations orally to mice. Immune responses against bromelain were detected by enzyme immunoassays. When formulated in antacid, oral bromelain retained substantial proteolytic activity throughout the gastrointestinal tract. Bromelain concentrations within the colon were dependent on both dose and formulation and were sufficient to remove bromelain-sensitive molecules from both leukocytes and colon epithelial cells. Peak activity in the stool was observed 4 h after oral dosing. Although anti-bromelain IgG was detected in both serum and stool after long-term oral therapy, these antibodies did not prevent bromelain proteolytic activity within the gastrointestinal tract. These studies demonstrate that bromelain enzymes can remain intact and proteolytically active within the murine gastrointestinal tract. They provide further support for the hypothesis that oral bromelain may potentially modify inflammation within the gastrointestinal tract via local proteolytic activity within the colonic microenvironment.
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PMID:Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice. 1499 17

Bromelain is an enzymatic complex obtained from pineapple (Ananas comosus) fruits and stem. Thermoseparation of bromelain by poly(ethylene oxide) (PEO)- poly(propylene oxide) (PPO)- poly(ethylene oxide) (PEO) block copolymers aqueous solutions was studied. Triblock copolymers with different EO percentages and different molecular mass were evaluated. Copolymer solutions at different pH values, buffer concentrations and copolymer concentrations were investigated. It was found that cloud point temperature increases as a function of %EO and decreases with copolymer molecular mass, copolymer concentration and buffer concentration. The results showed that all the studied factors influenced enzyme partition. The best conditions were copolymer with 10% EO and molecular mass of 2000 g/mol, temperature of 25 degrees C, copolymer concentration of 5% (w/w), pH 6.0 and salt concentration of 15 mM. Enzyme activity recovery around 79.5%, purification factor around 1.25 and activity partition coefficient around 1.4 were obtained.
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PMID:Bromelain partitioning in two-phase aqueous systems containing PEO-PPO-PEO block copolymers. 1517 61

Bromelain is a complex mixture of proteinases typically derived from pineapple stem. Similar proteinases are also present in pineapple fruit. Beneficial therapeutic effects of bromelain have been suggested or proven in several human inflammatory diseases and animal models of inflammation, including arthritis and inflammatory bowel disease. However, it is not clear how each of the proteinases within bromelain contributes to its anti-inflammatory effects in vivo. Previous in vivo studies using bromelain have been limited by the lack of assays to control for potential differences in the composition and proteolytic activity of this naturally derived proteinase mixture. In this study, we present model substrate assays and assays for cleavage of bromelain-sensitive cell surface molecules can be used to assess the activity of constituent proteinases within bromelain without the need for biochemical separation of individual components. Commercially available chemical and nutraceutical preparations of bromelain contain predominately stem bromelain. In contrast, the proteinase activity of pineapple fruit reflects its composition of fruit bromelain>ananain approximately stem bromelain. Concentrated bromelain solutions (>50 mg/ml) are more resistant to spontaneous inactivation of their proteolytic activity than are dilute solutions, with the proteinase stability in the order of stem bromelain>fruit bromelain approximately ananain. The proteolytic activity of concentrated bromelain solutions remains relatively stable for at least 1 week at room temperature, with minimal inactivation by multiple freeze-thaw cycles or exposure to the digestive enzyme trypsin. The relative stability of concentrated versus dilute bromelain solutions to inactivation under physiologically relevant conditions suggests that delivery of bromelain as a concentrated bolus would be the preferred method to maximize its proteolytic activity in vivo.
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PMID:Proteinase activity and stability of natural bromelain preparations. 1571 Mar 46

Bromelain, an extract from the pineapple plant, has been demonstrated to show anti-inflammatory and analgesic properties and may provide a safer alternative or adjunctive treatment for osteoarthritis. All previous trials, which have been uncontrolled or comparative studies, indicate its potential use for the treatment of osteoarthritis. This paper reviews the mechanism of its putative therapeutic actions, those clinical trials that have assessed its use in osteoarthritis to date, as well as considering the safety implications of this supplement for osteoarthritis and reviewing the evidence to date regarding the dosage for treating this condition. The data available at present indicate the need for trials to establish the efficacy and optimum dosage for bromelain and the need for adequate prospective adverse event monitoring in such chronic conditions as osteoarthritis.
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PMID:Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. 1584 Dec 58

Bromelain is a mixture of proteinases derived from pineapple stem that is marketed in health food stores as a "digestive aid". Orally administered bromelain was anecdotally reported to induce clinical and endoscopic remission of ulcerative colitis in two patients whose disease was refractory to multi-agent conventional medical therapy. However, the potential efficacy of bromelain in colitis has not yet been tested rigorously in either animals or humans. In this study, the clinical and histologic severity of inflammatory bowel disease (IBD) was determined in IL-10-/- mice treated orally with bromelain in vivo. Daily treatment with oral bromelain beginning at age 5 weeks decreased the incidence and severity of spontaneous colitis in C57BL/6 IL-10-/- mice. Bromelain also significantly decreased the clinical and histologic severity of colonic inflammation when administered to piroxicam-exposed IL-10-/- mice with established colitis. Proteolytically active bromelain was required for anti-inflammatory effects in vivo. Adverse effects of dermatitis, hair loss, and weight loss due to mucositis were rare, dose related, and were not seen in wild-type mice treated orally with up to 1000 mg bromelain/kg/day for 18 weeks. Although the exact mechanisms by which exogenous proteinases affect bowel inflammation have not yet been determined, the results justify additional studies of this complementary biologically based approach to treatment of IBD.
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PMID:Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease. 1593 49

Ileus continues to be a common consequence of abdominal surgery, causing significant patient discomfort and often leading to more serious problems. The therapy available is limited, hence, ileus remains an important clinical problem. Activation of inducible nitric oxide synthase (iNOS) directly modulates intestinal dysmotility after bowel manipulation and plays an essential role in initiating intestinal inflammation. Nuclear factor (NF)-kappaB is known to be a critical component of iNOS gene transcriptional activation in response to inflammatory stimuli. Bromelain is a crude extract from the pineapple stem, which is sold as a nutritional supplement to "promote digestive health" and as an anti-inflammatory medication in some developed countries. Here, we have found that oral administration of bromelain improves decrease in defecation in abdominal postoperative rats. Results showed that bromelain increased the wet weight, dry weight, water content and number of fecal pellets in laparotomized plus mechanically manipulated rats, suggesting improvement of postoperative ileus. Furthermore, bromelain treatment inhibited overexpressed iNOS mRNA and restored down-regulated inhibitor kappaBalpha mRNA in the colon of the postoperative rats. From the in vitro experiments, bromelain inhibits lipopolysaccharide (LPS)-induced nitrite overproduction in macrophage cell lines and LPS-induced NF-kappaB luciferase reporter gene expression in RAW264.7 macrophages transfected with NF-kappaB luciferase reporter gene. Thus, our findings suggest that bromelain improves decrease in defecation in postoperative rats, at least in part, by inhibiting colonic iNOS overexpression via NF-kappaB pathway. Our data indicates that bromelain may benefit patients with postoperative ileus.
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PMID:Bromelain improves decrease in defecation in postoperative rats: modulation of colonic gene expression of inducible nitric oxide synthase. 1613 11

Bromelain is a general name for a family of sulfhydryl-containing, proteolytic enzymes from the pineapple plant. The aim of the present study was to investigate the influence of bromelain on platelet count, platelet aggregation and platelet activity in vitro. Blood samples were taken from the antecubital vein of 10 healthy male non-smokers. Platelet count decreased after incubation with 2.5 and 5 mg bromelain/ml from 277 +/- 17 platelets/nl before to 256 +/- 21 and 247 +/- 19 platelets/nl after the treatment. The ADP and TRAP-6 induced platelet aggregation led to a significant decrease after the incubation with 2.5 mg (ADP: 48.6 +/- 25.7%; TRAP-6: 49.6 +/- 28.9%) or 5 mg (ADP: 5.0 +/- 4.6%; TRAP-6: 9.0 +/- 4.9%) bromelain/ml in comparison to control (ADP: 81.4 +/- 5.0%; TRAP-6: 77.4 +/- 10.4%). The percentage of unstimulated CD62P positive platelets which were investigated by flow cytometry was minimally higher after incubation with 5 mg bromelain/ml (0.57 +/- 0.48% PC) in comparison to control (0.22 +/- 0.11% PC), but after TRAP-6 stimulation the incubation with 5 mg bromelain/ml led to a remarkable decrease in comparison to the untreated control (50.4 +/- 20.2 to 0.9 +/- 0.8% PC). The changes of CD62P (TRAP-stimulated) and the results of platelet aggregation after incubation with bromelain in vitro may demonstrate the potential of bromelain as a substance for platelet inhibition.
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PMID:The influence of bromelain on platelet count and platelet activity in vitro. 1630 85

Bromelain inhibitor VI (BI-VI) is a cysteine proteinase inhibitor from pineapple stem and a unique two-chain inhibitor composed of two distinct domains. BI-VI's inhibitory activity toward the target enzyme bromelain is maximal at pH 4 and shows a bell-shaped pH profile with pKa values of about 2.5 and 5.3. This pH profile is quite different from that of bromelain, which is optimally active around pH 7. In the present article, to characterize the acidic limb, we first expressed the recombinant inhibitors designed to lose two putative hydrogen bonds of Ser7(NH)-Asp28(beta-CO2H) and Lys38(NH)-Asp51(beta-CO2H) and confirmed the existence of the hydrogen bonds by two-dimensional nuclear magnetic resonance (NMR). Moreover, it was revealed that these hydrogen bonds are not the essential electrostatic factor and some ionizable groups would be responsible for the acidic limb in the pH-inhibition profile. On the other hand, to characterize the basic limb, we examined the pH-dependent inhibition using the cysteine proteinase papain, some of whose properties differ from those of bromelain, and compared the data with the corresponding data for bromelain. The result suggests that the basic limb would be affected by some electrostatic factors, probably some carboxyl groups in the target proteinase.
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PMID:Characterization of the acidic and basic limbs of a bell-shaped pH profile in the inhibitory activity of bromelain inhibitor VI. 1631 42

Oral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNgamma and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction.
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PMID:Dose-dependent induction of IL-6 by plant-derived proteases in vitro. 1636 38

Bromelain has been reported to have anti-inflammatory and immunomodulatory effects. It has been cross-linked with organic acids and polysaccharides by gamma irradiation. The cross-linked (CL)-bromelain preparation resisted an acidic environment of pH 3 for 2 h and preserved 80% of its enzyme activity. Pretreatment of rats with CL-bromelain intragastrically for 7 days significantly reduced serum cytokine production induced by injected i.p. with 2.5 mg/kg of lipopolysaccharide (LPS). Bromelain significantly reduced serum glutamate-oxalacetate transaminase induced by LPS. The anti-inflammatory effect of CL-bromelain was correlated with reduced LPS-induced NF-kappaB activity and cyclooxygenase 2 (COX-2) mRNA expression in rat livers. In addition, CL-bromelain dose-dependently inhibited LPS-induced COX-2 mRNA and prostaglandin E2 (PGE2) in BV-2 microglial cells. CL-Bromelain also suppressed the LPS-activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). In conclusion, the anti-inflammatory effects of the CL-bromelain preparation in vivo and in vitro suggest its therapeutic potentials.
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PMID:Cross-linked bromelain inhibits lipopolysaccharide-induced cytokine production involving cellular signaling suppression in rats. 1653 95


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