No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
The mechanism of the physiological action of bromelain
Abstract
The pineapple protease, bromelain, selectively inhibits the biosynthesis of proinflammatory prostaglandins, apparently by indirect action.The inhibition of endogenous proteases that accompanies trauma, or prolonged exposure to excessive stress markedly elevates the relative proportions of those prostaglandins responsible for the symptoms of inflammation. It has been demonstrated that bromelain's specificity is similar to that of the endogenous protease plasmin. Bromelain acts on fibrinogen to give products that are similar, at least in effect, to those formed by plasmin. They are small molecular weight active peptides, which regulate prostaglandin biosynthesis and create conditions existing in the healthy organism. It has been shown that a substantial portion of orally administered bromelain is absorbed intact into the bloodstream, thereby elevating the proteolytic and fibrinolytic activity of the blood for hours.The similarity between the beneficial effects of aspirin-type drugs and bromelain, while bromelain causes none of the undesirable side effects of the others, suggests that bromelain acts on the prostaglandin synthetic pathway at a site different from that affected by the non-steroidal anti-inflammatory drugs. While aspirin inhibits the cyclooxygenase and thus the biosynthesis of prostaglandins, it is postulated that bromelain acts further down the arachidonate cascade at the thromboxane synthetase step. Circumstantial evidence suggests that bromelain inhibits the synthesis of the “proinflammatory” prostaglandins without affecting that of the “anti-inflammatory” ones. Bromelain therefore tends to reestablish the balance of the two types of prostaglandins that characterizes the state of the healthy organism.
... Physiologic actions of bromelain include: anti-inflammatory action, smooth muscle relaxation, inhibition of blood platelet aggregation, improved wound healing, and when taken with meals, enhanced digestion. [28][29][30][31][32][33][34][35][36][37][38] Several mechanisms may account for bromelain's widely utilized anti-inflammatory effects: 1) enhanced proteolytic activity at sites of inflammation; 2) fibrinolysis activity via the plasminogen-plasmin system; 3) depletion of kininogen; and 4) inhibition of biosynthesis of pro-inflammatory prostaglandins and induction of PGE-1 accumulation. 29,31,32,38 While bromelain has been demonstrated to be absorbed intact (up to 40% of ingested amount), the proteolytic actions are inhibited by serum factors, 31,32 suggesting that the first mechanism has only limited effect under normal circumstances. ...
... [28][29][30][31][32][33][34][35][36][37][38] Several mechanisms may account for bromelain's widely utilized anti-inflammatory effects: 1) enhanced proteolytic activity at sites of inflammation; 2) fibrinolysis activity via the plasminogen-plasmin system; 3) depletion of kininogen; and 4) inhibition of biosynthesis of pro-inflammatory prostaglandins and induction of PGE-1 accumulation. 29,31,32,38 While bromelain has been demonstrated to be absorbed intact (up to 40% of ingested amount), the proteolytic actions are inhibited by serum factors, 31,32 suggesting that the first mechanism has only limited effect under normal circumstances. The latter three mechanisms are closely interrelated, since after tissue injury, the kinin, complement, fibrinolytic and clotting systems are all activated. ...
... [28][29][30][31][32][33][34][35][36][37][38] Several mechanisms may account for bromelain's widely utilized anti-inflammatory effects: 1) enhanced proteolytic activity at sites of inflammation; 2) fibrinolysis activity via the plasminogen-plasmin system; 3) depletion of kininogen; and 4) inhibition of biosynthesis of pro-inflammatory prostaglandins and induction of PGE-1 accumulation. 29,31,32,38 While bromelain has been demonstrated to be absorbed intact (up to 40% of ingested amount), the proteolytic actions are inhibited by serum factors, 31,32 suggesting that the first mechanism has only limited effect under normal circumstances. The latter three mechanisms are closely interrelated, since after tissue injury, the kinin, complement, fibrinolytic and clotting systems are all activated. ...
Carpal tunnel syndrome (CTS) is a neuropathy caused by entrapment and compression of the median nerve as it passes through the carpal tunnel in the wrist, leading to a decrease in nerve transmission to and from the hand. Symptoms include pain, numbness, tingling, aching, and loss of motor and sensory function in the first three digits of the hand. These symptoms are typically worse at night and can awaken the individual. CTS is more common in women than men, and is a common occurrence in occupations involving repetitive motions of the upper extremity. A vitamin B6 deficiency has been found in many patients with CTS, and treatment with B6 or its bioactive form, pyridoxal 5' phosphate, is helpful in the majority of cases. Addressing the individual's occupational biomechanical and/or ergonomic factors, in addition to manual manipulation and the therapeutic use of anti-inflammatory substances such as bromelain can be of significant benefit and may decrease the need for carpal tunnel release surgery. (Alt Med Rev 1997;2(1):26-35)
... It has beenshownthat this fibrinolytic agent promotes reabsorption of edema in the blood circulation (6); it reduces swelling, bruising, pain, and healing time after trauma and surgical procedures (5). Evidence has shown that bromelain digests fibrin, thus allowing the elimination of edema (7). Indirectly, bromelain increases the time required for the conversion of prothrombin into thrombin, and thus activating plasminogen into plasmin; by these means, it prevents the formation of fibrin (7). ...
... Evidence has shown that bromelain digests fibrin, thus allowing the elimination of edema (7). Indirectly, bromelain increases the time required for the conversion of prothrombin into thrombin, and thus activating plasminogen into plasmin; by these means, it prevents the formation of fibrin (7). All these cause a reduction in vascular permeability. ...
Objectives: To evaluate the anti-inflammatory and analgesic effect of Bromelain (pineapple extract) administered orally in the postoperative after extraction of impacted lower molars.
Study Design: This is a prospective, placebo-controlled, unicentric, double-blind study; the sample size was 34 patients. The pre and postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included inflamtion, pain and oral aperture, as well as the need for analgesics. One group received bromelain 150mg per day for three days and 100mg on days 4 to 7. The other group received placebo in the same dosage. All outcomes werrecorded quantitatively and analyzed with the Mann-Whitney U test for independent samples.
Results: Although there were no statistically significant differences between the treatment groups, a trend towards less inflammation and improved oral aperture was observed in the group that received bromelain, compared to the group that received placebo. This trend can be attributed completely to random reasons, since there is no statistical difference in the results.
Conclusions: Further studies are necessary to analyze different administration patterns and doses of bromelain for the use in the postoperative of impacted third molars.
Key words:Tooth extraction, third molar, postoperative period, bromeline, clinical study.
... Additionally, research indicates that atherosclerotic plaques are stabilized by a fibrous cap primarily composed of collagen. The proteolytic activity of bromelain could theoretically lead to the degradation of this collagen, potentially compromising the stability of the plaque [82]. This destabilization may increase the risk of plaque rupture, which is a critical event that can precipitate acute cardiovascular events, such as myocardial infarction [83]. ...
Background
The use of complementary and alternative medicine is becoming increasingly important in the prevention and management of complications related to diabetes.
Methods
A comprehensive literature search was conducted across major databases (EMBASE, Scopus, PubMed, Google Scholar, Web of Science, Cochrane Library) up to December 2024. The search focused on studies examining the effect of bromelain on glycemic control, lipid profiles, and related mediators in diabetes.
Key findings
Bromelain supplementation demonstrated positive effects on key metabolic markers. Bromelain may stimulate AMPK in muscle cells, enhancing glucose uptake and utilization, potentially lowering blood glucose levels, and benefiting individuals with diabetes. Although direct evidence of bromelain’s impact on incretin levels is limited, its ability to modulate gastrointestinal function and improve nutrient absorption could indirectly influence incretin secretion. Moreover, Peptides or smaller amino acids resulting from bromelain’s proteolytic activity enter the bloodstream and potentially enhance nutrient absorption, which plays an important role in evaluating the therapeutic potential of bromelain in diabetes management.
Conclusion
Bromelain supplementation is effective in improving glycemic and lipid indices in diabetes. However, further research is needed to clarify the underlying mechanisms, including bromelain’s potential interaction with the incretin system and its role in modulating insulin resistance through various pathways.
... It interacts with lipoxygenases, increasing plasmin production. Plasmin's fibrinolytic action reduces localised oedema and the synthesis of pro-inflammatory prostaglandins [6,7]. ...
... Bromelain is a glycoprotein with an oligosaccharide in its molecular structure consisting of xylose, mannose, fucose, and N-acetyl glucosamine. Bromelain has strong medicinal potency and contains many proteinase inhibitors [10,11]. Bromelain is extracted from the juice of cooled pineapple that passes through various downstream procedures resulting in the production of a yellow powder. ...
Bromelain is a protein digestive enzyme obtained from the extract of pineapple (steam, fruit, and leaves). It is a cocktail of several thiol endopeptidases and other components like peroxidase, cellulase, phosphatase, and several protease inhibitors. It is a glycoprotein with an oligosaccharide in its molecular structure that contains xylose, fucose, mannose, and N-acetyl glucosamine. Many approaches have been used in the extraction and purification of bromelain like filtration, membrane filtration, INT filtration, precipitation, aqueous two-phase system, ion-exchange chromatography, etc. This enzyme is widely used in the food industry for meat tenderization, baking, cheese processing, seafood processing, etc. However, this enzyme also expands its applicability in the food industry. It is reported to have the potential for the treatment of bronchitis, surgical trauma, sinusitis, etc. The in vitro and in vivo studies showed that it possesses fibrinolytic, anti-inflammatory, antithrombotic, anti-edematous activity, etc. The human body absorbed bromelain without any side effects or reduction in its activity. However, in some cases, it shows side effects in those patients who are allergic to pineapple. To minimize such adverse effects bromelain is immobilized inside the nanoparticles. This paper gives an overview of the production, purification, and application of this industrially important enzyme in the food and pharmaceutical industry. It also discusses the various immobilization strategies used to enhance its efficiency.
... It inhibits the synthesis of the "proinflammatory" prostaglandins without affecting that of the "antiinflammatory" properties. 9 Previously done studies have shown the effect of orally administered bromelain in reducing the postsurgical complications; these studies suggested few mechanisms of actions such as -(1) Altering pain mediators such as bradykinin, (2) Inhibiting the synthesis of pro-inflammatory prostaglandins, mainly PGE2 and (3) Its fibrinolytic action aids in the reabsorption of edema into the blood circulation. 4 Tejpal singh et.at. ...
Surgical removal of third molars is still the most common routine surgical procedure done by oral and maxillofacial surgeons which is usually associated with postoperative sequelae. In order to avoid or minimize post-surgical complications such as swelling, pain and trismus, patients are advised to use proteolytic enzyme and NSAID’s along with routine antibiotics.
50 patients who have bilateral symmetrical impacted mandibular third molars were included in the study. Post operatively, all patients were given antibiotics and analgesics for 5 days. Patients were given bromelain for 5 days after the procedure on one side and trypsin-chymotrypsin for 5 days on the other side with an interval of 21 days between the two procedures. Patients were recalled on day 1, day 3 and day 7 for assessment of post- operative trismus, pain and swelling based on measuring inter-incisal distance, visual analogue scale and, facial reference points.
Data was gathered and statistical assessment was done using SPSS software by using descriptive statistics and chi square test.
The conclusion drawn from the study was that bromelain has a significant effect on swelling, mouth opening and pain after surgical removal of impacted third molar than chymotrypsin. We suggest its usage in reduction of swelling and pain post operatively after surgical removal of third molar. However further studies with larger sample size and randomizations are required to confirm the same.
... However, these results are yet to be amalgamated and critically compared so as to make out whether bromelain will gain wide acceptance as a phytomedicinal supplement [8]. Bromelain acts on fibrinogen giving products that are similar, at least in effect, to those formed by plasmin [9]. Experiment in mice showed that antacids such as sodium bicarbonate preserve the proteolytic activity of bromelain in the gastrointestinal tract [10]. ...
Bromelain is a protein digesting enzyme that can be purchased commercially from the Ananas comosus (pineapple) fruit or stem. Bromelain from the fruit and bromelain from the stem are prepared differently and have different enzymatic compositions. Bromelain usually refers to the "stem bromelain." Bromelain is made up of a variety of thiol endopeptidases as well as other enzymes and inhibitors such as phosphatase, glucosidase, peroxidase, cellulase, and esterase. Bromelain has been shown to have fibrinolytic, anti-oedematous, antithrombotic, and anti-inflammatory properties in vitro and in vivo studies. Bromelain is highly absorbable in the body, retaining its proteolytic activity while causing no significant side effects. Bromelain is responsible for a variety of therapeutic benefits, including angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis treatment, wound debridement, and improved drug absorption, particularly antibiotics. It also helps with osteoarthritis, diarrhoea, and a variety of cardiovascular problems. Bromelain also has anticancer properties and promotes cell death through apoptosis. This study examines bromelain's key properties and therapeutic applications, as well as its possible mechanism of action.
... Bromelain is known to possess antiinflammatory activity and has been shown to reduce blood viscosity, prevent the aggregation of blood platelets, and improve ischemia/reperfusion (I/R) injury in a skeletal muscle model (Juhasz et al. 2008). Bromelain acts on fibrin to facilitate fibrinolysis, thus helping to dissolve the clot and minimize the risk of arterial thrombosis (Taussig 1980;Kelly 1996). A recent study reported that bromelain is a potent anti-inflammatory compound evaluated against wound in rats (Fathi et al. 2020). ...
Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) – induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.
... Following contact with toxins and pathological substances such as BPA, the normal and physiological activities of the entire cell are disrupted, and lipid peroxidation occurs. In these cases, cell membranes such as plasma membranes, nuclear membranes, and mitochondria are prone to damage (30). With plasma membrane disintegration, cell cohesion is completely lost, thereby leading to premature cell death. ...
Background: Bisphenol A (BPA) is an endocrine-disrupting agent with a weak estrogenic effect. BPA causes testicular damage by reducing the activity of antioxidant enzymes. Bromelain (BROM) is a natural compound derived from pineapple, which is widely used as a dietary supplement with antioxidant properties. Objectives: The present study aimed to investigate the possible therapeutic effects of BROM on the testicular damage induced by BPA administration. Methods: This study was conducted on 40 adult male mice, which were divided into four groups of control (daily treatment with olive oil), BPA (600 mg/kg), BROM (70 mg/kg), and BPA + BROM. The treatments were administered orally for 35 consecutive days. Following that, the animals were euthanized by cervical dislocation, their testes were dissected, and morphometric evaluations (length, width, and thickness of testis) were performed. The epididymal tail was cut to release the sperms for sperm parameter assessment (count and motility). Afterwards, the testes were fixed in buffered formalin for histological examinations (number, diameter, and wall thickness of seminiferous tubules and the counts of spermatogenic, Sertoli, and Leydig cells). Results: All the indices of testicular morphology decreased significantly (P < 0.05) following BPA administration compared to the controls. In addition, the sperm parameters and Leydig and Sertoli cell counts indicated significant decremental effects on the animals administered with BPA compared to the controls (P < 0.05). After the administration of BROM in the BPA + BROM group, all the testicular morphometric indices increased significantly (P < 0.05) compared to the animals administered with BPA alone. These indices were the morphometric values of the testes, sperm parameters, cell counts, and seminiferous morphometric properties. Conclusions: According to the results, BROM could reduce the debilitative effects of BPA on the testes of the mice and protect the reproductive health of the animals against BPA-induced toxicity.
... Circumstantial evidence indicates the synthesis of the "proinflammatory" prostaglandins inhibited with bromelain without influencing the "anti-inflammatory" prostaglandins. Therefore, bromelain helps to restore the equilibrium of the two prostaglandins, which define the condition of the healthy organisms [44]. Though bromelain can be used in a wide range of areas (discussed in Table 1), the most traditional and established use of it is as an anti-inflammatory agent. ...
Bromelain is an effective chemoresponsive proteolytic enzyme derived from pineapple stems. It contains several thiol endopeptidases and is extracted and purified via several methods. It is most commonly used as an anti-inflammatory agent, though scientists have also discovered its potential as an anticancer and antimicrobial agent. It has been reported as having positive effects on the respiratory, digestive, and circulatory systems, and potentially on the immune system. It is a natural remedy for easing arthritis symptoms, including joint pain and stiffness. This review details bromelain’s varied uses in healthcare, its low toxicity, and its relationship to nanoparticles. The door of infinite possibilities will be opened up if further extensive research is carried out on this pineapple-derived enzyme.
... [9] Bromelain acts on fibrinogen giving products that are similar, at least in effect, to those formed by plasmin. [8] Mice model revealed that antacids such as sodium bicarbonate preserve the proteolytic activity of bromelain in the gastrointestinal tract. [10] Bromelain is considered as a food supplement and is freely available to the general public in health food stores and pharmacies in the USA and Europe. ...
S Bromelain is a protease enzyme derived from the stems of pineapples that is composed of a mixture of different thiol endopeptidases and other components. Bromelain is a mixture of different thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors. [14] In vitro and in vivo studies demonstrate that bromelain exhibits various anti edematous, antithrombotic, and anti-inflammatory activities. Bromelain is considerably absorbable in the body without losing its proteolytic activity and without producing any major side effects. Bromelain accounts for many therapeutic benefits like the treatment of angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics. It also relieves osteoarthritis, diarrhea, and various cardiovascular disorders. Bromelain also shows some potential in anti-cancerous activities and promotes cell death by apoptosis. The paper reviews the important properties and therapeutic applications of bromelain, along with the possible mode of action.
... The commercial form of Bromelain has no chemical analog, because if the enzyme is purified extremely, it loses its characteristics and natural properties. The main ingredient of Bromelain consists of proteolytic enzymes, though trace amounts of phosphatase acid, peroxidase, and several types of protein inhibitors are also found [8,9]. Among the effects of Bromelain are, antiinflammatory effect, and reduction of swelling and pain [10]. ...
Objective: To evaluate the effect of Anaheal (Bromelain) drug on the periodontal clinical indices in nonsurgical periodontal treatment of patients with chronic periodontitis. Material and Methods: In this double blind clinical trial, 80 patients with chronic moderate periodontitis and a healthy systemic status were chosen, and divided into two 40-subject groups. Thereafter, the standard treatment of periodontitis including scaling and root planning in one session by the unit operator was performed for all patients. Eventually, one group of the patients was administered Bromelain medication (500-mg capsule twice a day) one hour before food, while the other group was given placebo. Four and eight weeks after the treatment, the clinical periodontal indicators were measured and recorded in both groups. The data were assessed using descriptive statistics and analytical test methods (Mann-U-Whitney and Chi-square). P value less than 0.05 was considered statistically significant. Results: Gingival index, probing depth and plaque index before the treatment were similar in both groups (Anaheal and placebo). However, four and eight weeks after the treatment, the three studied indices were significantly lower in the Anaheal group as compared to the placebo (p<0.05). The index of bleeding on probing was also similar before the treatment and four weeks after the treatment in both groups. However, eight weeks after the treatment, this index was significantly lower in the Anaheal group as compared to the placebo group (p<0.05). Conclusion: Administration of oral Anaheal medication after nonsurgical periodontal treatments reduced all the clinical periodontal indices among patients with chronic periodontitis as compared to the control group. Therefore, it can be a suitable substitute for the common oral industrial antibiotics. © 2018, Association of Support to Oral Health Research (APESB). All rights reserved.
... Rutoside is a powerful anti-oxidants and effectively combat the harmful free radicals such as nitric oxide, released during the inflammatory process 22,23 . ...
... Codiase is also shown to exhibit antiplatelet activity [65]. Bromelain is known for its ability to activate factor XII and prekallikrein, and to hydrolyse cholesterol [68]. ...
The main function of proteases in any living organism is the cleavage of proteins resulting in the degradation of damaged, misfolded and potentially harmful proteins and therefore providing the cell with amino acids essential for the synthesis of new proteins. Besides this main function, proteases may play an important role as signal molecules and participate in numerous protein cascades to maintain the vital processes of an organism. Plant proteases are no exception to this rule. Moreover, in contrast to human-encoded enzymes, many plant proteases possess exceptional features such as higher stability, unique substrate specificity and a wide pH range for enzymatic activity. These valuable features make plant-derived proteolytic enzymes suitable for many biomedical applications, and furthermore, the plants can serve as factories for protein production. Plant proteases are already applied in the treatment of several pathological conditions in the human organism. Some of the enzymes possess antitumour, antibacterial and antifungal activity. The collagenolytic activity of plant proteases determines important medical applications such as the healing of wounds and burn debridement. Plant proteases may affect blood coagulation processes and can be applied in the treatment of digestive disorders. The present review summarizes recent advances and possible applications for plant proteases in biomedicine, and proposes the further development of plant-derived proteolytic enzymes in the biotechnology and pharmaceutical industries.
... Rutoside is a powerful anti-oxidants and effectively combat the harmful free radicals such as nitric oxide, released during the inflammatory process 22,23 . ...
Millions of patients worldwide with chronic musculoskeletal symptoms are on long term therapy with non-steroidal anti- inflammatory drugs (NSAIDs). But the unfortunate fact is that these drugs have common and potentially severe adverse effects, including renal impairment, gastrointestinal complications and cardiotoxicity. The cardiotoxic effect produced by these drugs is particularly worrying because many patients have both cardiovascular disease and musculoskeletal disease. Clinicians and medical researchers worldwide are in general agreement that pharmacologic pain treatment for musculoskeletal conditions is unsatisfactory and the irrationale use of NSAIDs in such conditions is adding the agony of the patients. Thus new drugs are needed to replace NSAIDs to treat musculoskeletal diseases. Newer natural and safer alternatives identified in recent past are Bromelain, Trypsin and Rutoside. Their combination to treat inflammatory diseases is a coming out with promising results.
... Bromelain seems to exert a wide range of therapeutic benefits; it is known to enhance absorption of drugs, particularly antibiotics [68,69]. Bromelain acts on fibrinogen giving products that are similar, at least in its effect, to those formed by plasmin [70]. Experiment in mice showed that antacids such as sodium bicarbonate preserve the proteolytic activity of bromelain in the gastrointestinal tract [71]. ...
The nonhormonal medical treatment can be divided into empirical, when the cause has not been identified, and nonempirical, if the pathogenic mechanism causing male infertility can be solved or ameliorated. The empirical nonhormonal medical treatment has been proposed for patients with idiopathic or noncurable oligoasthenoteratozoospermia and for normozoospermic infertile patients. Anti-inflammatory, fibrinolytic, and antioxidant compounds, oligo elements, and vitamin supplementation may be prescribed. Infection, inflammation, and/or increased oxidative stress often require a specific treatment with antibiotics, anti-inflammatory drugs, and/or antioxidants. Combined therapies can contribute to improve sperm quality.
... L. (V.) braziliensis, which gradually acquires its status of virulence necessary for mammalian infection. Generally, the presence of cathepsin-like in Leishmania sp inhibits biosynthesis of proinflammatory prostaglandins [52], thereby reducing clotting efficiency [53] and the possibility of influencing immune response in vertebrate hosts [8]. Furthermore, cathepsin L, but not cathepsin B, has the potential to generated kinins from high and low molecular weight kininogens -vasoactive peptides [54]. ...
Leishmania (Viannia) braziliensis presents adaptive protease-dependent mechanisms, as cysteine proteinases B (CPB). This work focuses on the expression of three cpb gene isoforms and CPB enzymatic activity during the parasite differentiation. Relative expression levels of LbrM.08.0810 gene was assessed, showing a higher quantity of transcripts in the logarithmic promastigotes phase than in the stationary promastigotes phase (> 1.5 times). The cbp gene tends to decrease during acid pH shock and increases when the temperature rises (> 1.3 times). LbrM.08.0820 and LbrM.08.0830 genes showed similar expression profiles to LbrM.08.0810 gene, with overall lower levels. The proteolytic activity shows a gradual increase during parasite's differentiation, with low levels in samples of logarithmic promastigotes phase (3.2 ± 0.08 mmol min-¹.mg protein⁻¹) to a peak of activity after 72 hours of incubation at 32ºC (4.2 ± 0.026 mmol min⁻¹.mg protein⁻¹), followed by a subsequent decrease of 68 % of peak activity levels after 96 hours of incubation at 32ºC (2.8 ± 0.37 mmol min⁻¹.mg protein⁻¹). These activities were also measured in presence of selective inhibitors for cysteine proteinases, as Z-Phe-Phe-fluoromethyl ketoneand and trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane, proving their source as cathepsin-like proteinases. These results indicate a modulation of cathepsin L-like expression during the L. (V.) braziliensis in vitro differentiation induced by acid pH and high temperature, for the first time.
... L. (V.) braziliensis, which gradually acquires its status of virulence necessary for mammalian infection. Generally, the presence of cathepsin-like in Leishmania sp inhibits biosynthesis of proinflammatory prostaglandins [52], thereby reducing clotting efficiency [53] and the possibility of influencing immune response in vertebrate hosts [8]. Furthermore, cathepsin L, but not cathepsin B, has the potential to generated kinins from high and low molecular weight kininogens -vasoactive peptides [54]. ...
... (10) Bromelain's specificity is similar to that of the endogenous protease plasmin which degrades fibrin to stimulate the synthesis of anti-inflammatory prostaglandins (7) and subsequently limits the spread of the coagulation process. (11,12) Bromelain may explain the possible mechanism linking impaired fibrinolysis and atherosclerosis associated with CVD in diabetes. (13) A systematic review suggested that there is more significant evidence from animal studies on the effect of bromelain on cardiovascular systems in animal models. ...
Objective
To assess whether the dietary supplement (bromelain) has the potential to reduce plasma fibrinogen and other cardiovascular disease (CVD) risk factors in patients with diabetes.
Methods
This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain (1,050 mg/day) on plasma fifibrinogen. This randomized controlled trial (RCT) recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years (standard deviation (SD), 12.62 years)] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg (3×350 mg) of either bromelain or starch-fifilled placebo capsules, two to be taken (2×350 mg) after breakfast and another (350 mg) after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks.
Results
The change in the fifibrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L (standard deviation (SD) 0.86g/L) compared with the mean reduction of 0.36 g/L (SD 0.96 g/L) for the placebo group. However, there was no signifificant difference in the mean change in fifibrinogen between the placebo and bromelain groups (mean difference=0.23g/L (SD 0.22 g/L), =0.291). Similarly, the difference in mean change in other CVD risk factors (blood lipids, blood pressure), blood glucose, C-reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically signifificant. Statistical differences in fifibrinogen between bromelain and placebo groups before the trial despite randomization may have inflfluenced the results of this study.
Conclusion
This RCT failed to show a benefificial effect in reducing fifibrinogen or inflfluencing other selected CVD risk factors but suggests other avenues for subsequent research on bromelain.
... These enzymes modulate arachidonate pathway in such a way that thromboxane production is decreased with no effect on cyclooxygenase. This leads to decrease in oedema and inflammation [10]. Enzymes such as rutin are strong antioxidants and effectively combat the harmful free radicals such as nitric oxide released during inflammatory process [11]. ...
Enzymes are complex macromolecules of amino acids which biocatalyse various body processes. The aim of this study is to evaluate the effect of oral enzymes for control of infection and inflammation in post operative septoplasty cases. 40 patients planned for septoplasty under general anaesthesia were taken up for study. 20 patients were included in group E and were given a combination of oral enzymes postoperatively. Remaining 20 patients were included in group D and were given diclofenac and paracetamol combination postoperatively. Patients were evaluated post operatively after 1, 2 and 4 weeks for post operative pain , swelling , congestion , patient satisfaction and other criterias. The results showed that pain and swelling was significantly less in oral enzymes group . There was less nasal obstruction , discharge and more patient satisfaction in enzyme group. There were less complications in enzyme group. So it can be concluded that oral enzymes are more effective for control of infection and inflammation in post operative septoplasty cases.
... Rutoside is a powerful anti-oxidants and effectively combat the harmful free radicals such as nitric oxide, released during the inflammatory process 22,23 . ...
... In the environment of the sandfly gut, a pH near neutrality may be favorable for the catalysis of some substrates necessary to the promastigotes nutrition. Also, it is known that enzymes that hydrolyze the pEFLpNan substrate can inhibit the biosynthesis of proinflammatory prostaglandins (Taussig 1980) and reduce clotting efficiency by affecting fibrinogen (Livio et al. 1978). Moreover, our results indicated that the proteinases are capable of hydrolyzing different peptide bonds, since they were capable of degrading substrates having multiple (gelatin) or defined peptide bonds (pEFLpNan). ...
Leishmania (Viannia) braziliensis is the major
causative agent of American tegumentary leishmaniasis, a
disease that has a wide geographical distribution and is a
severe public health problem. The cysteine proteinase B
(CPB) from Leishmania spp. represents an important
virulence factor. In this study, we characterized and localized
cysteine proteinases in L. (V.) braziliensis promastigotes. By
a combination of triton X-114 extraction, concanavalin Aaffinity,
and ion exchange chromatographies, we obtained an
enriched fraction of hydrophobic proteins rich in mannose
residues. This fraction contained two proteinases of 63 and
43 kDa, which were recognized by a CPB antiserum, and
were partially sensitive to E-64 in enzymatic assays with the
peptide Glu-Phe-Leu. In confocal microscopy, the CPB
homologues localized in the peripheral region of the parasite.
This data together with direct agglutination and flow
cytometry assays suggest a surface localization of the CPB
homologues. The incubation of intact promastigotes with
phospholipase C reduced the number of CPB-positive cells,
while anti-cross-reacting determinant and anti-CPB antisera
recognized two polypeptides (63 and 43 kDa) derived from
phospholipase C treatment, suggesting that some CPB
isoforms may be glycosylphosphatidylinositol-anchored.
Collectively, our results suggest the presence of CPB
homologues in L. braziliensis surface and highlight the need
for further studies on L. braziliensis cysteine proteinases,
which require enrichment methods for enzymatic detection
... However, these results are yet to be amalgamated and critically compared so as to make out whether bromelain will gain wide acceptance as a phytomedical supplement [8]. Bromelain acts on fibrinogen giving products that are similar, at least in effect, to those formed by plasmin [9]. Experiment in mice showed that antacids such as sodium bicarbonate preserve the proteolytic activity of bromelain in the gastrointestinal tract [10]. ...
Bromelain belongs to a group of protein digesting enzymes obtained commercially from the fruit or stem of pineapple. Fruit bromelain and stem bromelainare prepared differently and they contain different enzymatic composition. "Bromelain" refers usually to the "stem bromelain." Bromelain is a mixture of different thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors. In vitro and in vivo studies demonstrate that bromelain exhibits various fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities. Bromelain is considerably absorbable in the body without losing its proteolytic activity and without producing any major side effects. Bromelain accounts for many therapeutic benefits like the treatment of angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics. It also relieves osteoarthritis, diarrhea, and various cardiovascular disorders. Bromelain also possesses some anticancerous activities and promotes apoptotic cell death. This paper reviews the important properties and therapeutic applications of bromelain, along with the possible mode of action.
... In the environment of the sandfly gut, a pH near neutrality may be favorable for the catalysis of some substrates necessary to the promastigotes nutrition. Also, it is known that enzymes that hydrolyze the pEFLpNan substrate can inhibit the biosynthesis of proinflammatory prostaglandins (Taussig 1980) and reduce clotting efficiency by affecting fibrinogen (Livio et al. 1978). Moreover, our results indicated that the proteinases are capable of hydrolyzing different peptide bonds, since they were capable of degrading substrates having multiple (gelatin) or defined peptide bonds (pEFLpNan). ...
Leishmania (Viannia) braziliensis is the major causative agent of American tegumentary leishmaniasis, a disease that has a wide geographical distribution and
is a severe public health problem. The cysteine proteinase B (CPB) from Leishmania spp. represents an important virulence factor. In this study, we characterized and localized cysteine proteinases in L. (V.) braziliensis promastigotes. By a combination of triton X-114 extraction, concanavalin A-affinity, and ion exchange chromatographies, we
obtained an enriched fraction of hydrophobic proteins rich in mannose residues. This fraction contained two proteinases of
63 and 43kDa, which were recognized by a CPB antiserum, and were partially sensitive to E-64 in enzymatic assays with the
peptide Glu-Phe-Leu. In confocal microscopy, the CPB homologues localized in the peripheral region of the parasite. This data
together with direct agglutination and flow cytometry assays suggest a surface localization of the CPB homologues. The incubation
of intact promastigotes with phospholipase C reduced the number of CPB-positive cells, while anti-cross-reacting determinant
and anti-CPB antisera recognized two polypeptides (63 and 43kDa) derived from phospholipase C treatment, suggesting that
some CPB isoforms may be glycosylphosphatidylinositol-anchored. Collectively, our results suggest the presence of CPB homologues
in L. braziliensis surface and highlight the need for further studies on L. braziliensis cysteine proteinases, which require enrichment methods for enzymatic detection.
... In summary, despite the high trypanocidal profiles, our results indicated that b-lapachone and Epoxy-a-lap affects T. cruzi through different pathways since they may act as inhibitors of different proteinases groups. b-Lapachone inhibits thiol-containing proteinases and probably affects T. cruzi during infection of mammal cells as well as in biosynthesis of proinflammatory prostaglandins reducing clotting efficiency (Livio et al., 1978; Taussig, 1980). Meanwhile Epoxy-a-lap affects serine-proteinases and interferes on the mammalian host cell invasion and infection establishment (Caler et al., 1998). ...
In this study we compared the effects of naphthoquinones (α-lapachone, β-lapachone, nor-β-lapachone and Epoxy-α-lap) on growth of Trypanosoma cruzi epimastigotes forms, and on viability of VERO cells. In addition we also experimentally analyzed the most active compounds inhibitory profile against T. cruzi serine- and cysteine-proteinases activity and theoretically evaluated them against cruzain, the major T. cruzi cysteine proteinase by using a molecular docking approach. Our results confirmed β-lapachone and Epoxy-α-lap with a high trypanocidal activity in contrast to α-lapachone and nor-β-lapachone whereas Epoxy-α-lap presented the safest toxicity profile against VERO cells. Interestingly the evaluation of the active compounds effects against T. cruzi cysteine- and serine-proteinases activities revealed different targets for these molecules. β-Lapachone is able to inhibit the cysteine-proteinase activity of T. cruzi proteic whole extract and of cruzain, similar to E-64, a classical cysteine-proteinase inhibitor. Differently, Epoxy-α-lap inhibited the T. cruzi serine-proteinase activity, similar to PMSF, a classical serine-proteinase inhibitor. In agreement to these biological profiles in the enzymatic assays, our theoretical analysis showed that E-64 and β-lapachone interact with the cruzain specific S2 pocket and active site whereas Epoxy-α-lap showed no important interactions. Overall, our results infer that β-lapachone and Epoxy-α-lap compounds may inhibit T. cruzi epimastigotes growth by affecting T. cruzi different proteinases. Thus the present data shows the potential of these compounds as prototype of protease inhibitors on drug design studies for developing new antichagasic compounds.
... We propose that through the combined use of enzymatic activity and gene expression approaches the expression of CPs is modulated during successive in vitro passages of L. (V. ) braziliensis promastigotes, suggesting that these enzymes might be involved with adaptive and selective changes during the life cycle of this parasite. Additionally, the decrease in pEFLpNan substrate hydrolysis may indicate a decrease of promastigote virulence in mammalian infection, since thiol-containing proteinases can inhibit the biosynthesis of proinflammatory prostaglandins (Taussig, 1980) and reduce clotting efficiency by affecting fibrinogen (Livio et al., 1978). ...
Cysteine proteinases are an important virulence factor in Leishmania parasites. In this study we analyzed the cysteine proteinase expression of infective Leishmania (Viannia) braziliensis promastigotes, examining the expression induced by successive in vitro passages in culture. We observed that this parasite presents a decrease in its virulence over BALB/c macrophages, after successive passages in culture, but still they present proteinase activity, being capable of hydrolyzing the substrate pGlu-Phe-Leu-p Nitroanilide at pH 7.0. This proteinase activity also decreases in the course of the successive passages. Additionally, the decrease in the amount of CPB proteins following successive passages of promastigotes was verified by immunoblotting assays, using an anti-CPB antiserum. Real-time PCR assays were performed to assess the relative cpb expression when compared to a housekeeping gene in promastigote cDNA preparations from the first, fourth and seventh passages. Interestingly, the data indicate a relative increase in cpb gene transcripts as the promastigotes were maintained under in vitro culture: 2.2 times higher for fourth and 2.7 times higher for seventh passages when compared to the first passage. Thus, the information gathered here shows that the expression of cysteine proteinases is modified during in vitro cultivation of L. (V.) braziliensis promastigotes.
... In the field of antidoping research, interest has recently focused on proteases that can be discreetly added by athletes to urine specimens at some point during the collection procedure to mask the application of hormones such as EPO. A good number of bacterial alkaline proteases are very common and inexpensive and are present in various household products, with major applications as detergent enzymes [82,83,85,86] and nutritional supplements [87]. Hence, their misuse for urine manipulation is likely and efficient [88]. ...
According to the World Anti-doping Agency (WADA) Code for the collection of sport urine samples, no stabilization method is applied in the sample collection equipment system in order to prevent degradation of urine compounds. However, urine sample transport conditions are not always consistent with proper storage and handling of samples. During this period, microorganisms present in the sample rapidly increase in number and may affect sample constituents. Furthermore, the possibility of intentional contamination of sports samples during sample collection with microbes or proteolytic enzymes in order to adulterate samples by masking the abuse of prohibited substances cannot be excluded. Consequently, urine samples should be stabilized with a suitable method in a way that protects the integrity of the samples. The present study, conducted within the framework of a WADA research grant, examines physical and chemical methods of preventing microbial or other deterioration in urine samples for doping control purposes.
Emerging on the horizon in cancer therapy is an expansion of the scope of treatment beyond cytotoxic approaches to in clude 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 relation ship 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 sug gests 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, andoxi dants, boswellia, bromelain, curcumin, and quercetin) that favorably influence eicosanoid production.
Background:
This study aimed to compare the analgesic effects of Ibuprofen and bromelain after periodontal surgery.
Methods:
A double-blinded crossover clinical trial was conducted on 22 patients needing two crown lengthening surgeries without bone surgery or with limited bone surgery on two quadrants of the maxilla, with control and test sides. Each quadrant was randomly assigned to bromelain (500 GUD) or ibuprofen (400 mg). Immediately after the surgery and 6 hours after it, the first dose of the drugs was packaged in the same capsules in A and B. Postoperative pain was evaluated during the first 8 hours and on the following day using a visual analog scale (VAS).
Results:
Using the VAS, the Ibuprofen group showed significantly lower mean pain scores than the bromelain group at 4 hours (P=0.047). In contrast, there were no significant differences between the two groups at 2, 6, 8, 10, 12, 24, and 48 hours (P>0.05).
Conclusion:
The effectiveness of bromelain for pain control following periodontal surgery was comparable to that of Ibuprofen. Therefore, bromelain can be an efficient replacement for ibuprofen in managing pain after periodontal surgery, especially in patients with gastric ulceration and increased bleeding tendency.
Bromelain, a dietary supplement of cysteine protease family having promising results against thrombosis is gaining attention. Yet poor mechanical stability, gastric instability, high oral dose and poor patient compliance restricted its clinical application. Therefore, acid stable bromelain loaded hybrid solid lipid nanoparticles (Br-HNPs) were fabricated and characterized for their contribution to in-vivo stability and therapeutic efficacy in thrombosis management. Comprehensive optimization of various process and formulation variables ensued the formation of nano-sized (120.56±40.12nm) Br-HNPs with entrapment efficiency of 86.32±5.56%. Spherical core shell framework of Br-HNPs prolonged drug release and provided in-vivo and storage stability at room temperature. Br-HNPs significantly inhibited platelet aggregation without affecting bleeding time and dissolved thrombus at 1.91-fold higher efficacy compared to bromelain. Furthermore, Br-HNPs prevented hypercoagulation states and suppressed cytokines production significantly (p<0.05) contributing to its antiplatelet activity. These findings indicated that Br-HNPs could serve a promising alternative to commercial therapies for management of thrombotic disorders.
The purposes of this study were to produce prototypes of new chemo-mechanical caries removal reagents that contained bromelain and orange oil and to evaluate their effectiveness and quality for caries removal and the influence on resin filling after caries removal. Sixty extracted human permanent teeth with cervical dentinal caries were used in this study. BO reagent I containing 10% bromelain and 10% orange oil and BO reagent II containing 10% bromelain and 20% orange oil were produced for this study. All specimens were classified into three groups and for each group either BO reagents or Carisolv were used to remove caries. After caries removal, all specimens in each group were divided into 5 non-EDTA and 15 EDTA treatment teeth. The cavity surfaces of 5 non-EDTA and 5 EDTA treatment teeth were observed by stereomicroscopy and scanning electron microscopy (SEM). Other specimens were filled with resin composite and 5 teeth were selected in each group, and then a micro-leakage test was performed. After the micro-leakage test, all samples were longitudinally bisected with a diamond saw disc, and observed by stereomicroscopy and SEM. Five residual teeth in each group were immersed in 4 N HCL to resolve dentin and the condition of their resin tag was observed by SEM. No significant difference in surface structure was found among the three groups. The surfaces of non-EDTA treatment cavities showed a remaining smear layer in all groups, while the smear layer had been completely removed after EDTA treatment. The results of the micro-leakage test of each group were also equivalent. Sufficient bonding between resin composite and dentin was confirmed in all groups by SEM. The time required for caries removal by treatment with BO reagents was shorter than that by Carisolv treatment where BO reagent II showed the statistically shortest time. The presence of resin tags was confirmed by SEM in all groups. These results indicated that BO reagents can remove caries and do not influence the bonding between resin composite and dentin. In conclusion, the new reagent, especially BO reagent II, is expected to be an effective agent for caries removal.
Lumbar spine osteoarthritis with 40-85% prevalence, degeneration of spine with remarkable narrowing of disc space and osteophytes formation trigger pain in lower back. Pain in lower portion of back is now considered to be the second most commonly treated health issue in primary health care setups. This pain causes disability, functional loss and job absentees. Commonly pain is managed pharmacologically by NSAIDS but resulted in severe gastric side effects. The purpose of this trial was to appraise the properties of bromelain and papain, the vegetal proteolytic enzymes, in comparison with standard drug on LBP patients. Forty men and women with lumbar spine osteoarthritis were recruited and divided into group 1, received aceclofenac 100mg tablet b.i.d as standard treatment, group 2, patients treated with aceclofenac 100 mg tablet b.i.d and enzyme supplements 250 mg b.i.d for 6 weeks. All the participants were evaluated for their body mass index, vital signs and liver/kidney enzymes before and after treatment. Moreover intensity of pain were also measured through visual analogue scale (VAS) and oswestry low back pain questionnaire (ODI) before treatment (0 week), 3rd week and 6th week of treatment. The enzyme group patients showed significantly diminished pain scores VAS from 7.10±1.29 to 5.85±1.531*** (P=0.001), ODI score from 56.2±8.70 to 51.6±8.125*** (P=0.000), significantly diminished enzymes; ALP from 210.00±55.24 to 196.90±51.02 (P=0.054*) and serum creatinine from 0.97±0.153 to 0.87±0.139 (P=0.035*) and improved quality of life. Hence, this study suggested that the enzyme supplements for 6 weeks have prolonged beneficial carry-over effects in comparison to standard treatment without producing any change in BMI (P>0.05) and vital signs (P> 0.05).
Autotrasplantation of impacted wisdom tooth for sostitution of second molar irremediably compromised: case report
Summary
Dental transplants are a frequently forgotten chapter of dentistry, even though it is a technique validated by literature. The conclusions of all available articles are unanimous in asserting that autotransplantion is a reliable therapy with high long-term success rates. In many clinical cases, dental autotransplantation should be the first therapeutic choice, while implantology should be considered only in the event of transplant failure. Instead, clinicians often plan an implant rehabilitation even where there is a specific indication of transplantation. Obviously, the selection of cases is more selective in dental transplants than implant rehab and it is not always possible to opt for this surgical technique, either due to the lack of a suitable donor element or for an inadequate recipient site. Ideal cases are those where autotrasplantation does not generate significant biological costs for the patient, as in the case of alignement of impacted teeth when the orthodontic therapy is inapplicable or as in the case of substitution of compromised teeht with non-functional element. In the case of this article a second inferior molar had to be extracted, and in order to perform an implant rehabilitation it was also necessary to extract the contiguous wisdom tooth. Therefore, transplantation was the first choice, while implantology would only be considered in the event of transplant failure. The transplanted tooth of this article has a four years follow up with a clinical and radiological condition that makes it indistinguishable from a tooth originated in the recipient socket.
Introduction: This study examines the effects of bromelain supplementation on anatomical-structural (interstitial edema), biological and functional features of strength markers of muscle damage, caused by physical exercise with eccentric component, intensified in some groups with a supplementation of vascular occlusion. The objective is to assess whether bromelain is helpful to reduce the clinic associated with DOMS and facilitate the recovery of muscle strength after eccentric work. Material and methods: A pilot study, quasi-experimental multicenter, randomized, double-blind, parallel, placebo controlled trial. We selected healthy male volunteers, randomly divided into the following groups: No occlusion Supplemented with bromelain (GES) and Placebo (GEP), with occlusion Supplemented with bromelain (GEOS) and Placebo (GEOP). In all subjects was assessed muscle pain, explosive strength (squat jump and counter movement jump), biological signs of cytolysis (creatmfosfo kinase, lactate dehydrogenase and creatinine), and global and segmental interstitial edema. The tests were performed just before (Tl), immediately after eccentric exercise (T2), at 24h (T3), 48h (T4) and 72 h (T5). Subjects in the supplemented group received bromelain extract (50 mg Fortilase, Rottapharm, SL), (100 mg, 30 minuts prior to exercise and 50 mg at the end of the session), while the other group received placebo, both in the form of tablets. Results and conclusions: Forty-four healthy older men (20.49± 1.70) were analyzed. The supplementation with bromelain is effective in reducing the pain associated with DOMS at all stages, especially at 48 hours post-injury favoring a faster decrease in pain. Prevents and neutralizes acute intramuscular edema occurred in the execution of an eccentric exercise component. Decreases the loss of explosive strength after the completion of a job eccentric work accelerating tissue repair after the injury. These results demonstrate that bromelain supplementation prevents early cytolysis, thus promoting regeneration in very early stages of muscle injury and maintaining its effect in the inflammatory phase of injury. All this allows to improve muscle recovery and reduce injuries related to physical work with eccentric component.
This study was aimed to investigate the effects of bromelain on angiogenesis, nitric oxide, and matrix metalloproteinase-3 and -9 in rats exposed to 1200mV electrical burn injury. Thirty-five, male Wistar albino rats was divided into five groups (n=7 each), including control (untreated) group; electrical burn injury (EI) group; electrical burn injury+21.25mg/kg BW bromelain group (EIB1); electrical burn injury+42.50mg/kg BW bromelain group (EIB2); and electrical burn injury+85.00mg/kg BW bromelain group (EIB3). Rat models of electrical burns done by providing electricity in rats that had been anesthetized, a voltage of 1200mV and strong currents 15mA for 10s. The VEFG, NO, and MMP-9 levels were significantly greater in the EI group compared to the untreated group. Out of the 21.25mg/kg BW, 42.50mg/kg BW, and 85mg/kg BW doses of Bromelain extract, only the lowest doses prevented EI-induced increase in NO and MMP-9 level (P<0.05). Bromelain at the lowest dose (21.25mg/kg BW) act as anti-inflammatory and modulate the matrix metalloproteinase-9 in rats exposed to 1200mV electrical burn injury.
The antiedematous and antiinflammatory potential of the proteolytic enzymes trypsin, chymotrypsin, bromelin and papain, and the flavonoid rutosid were investigated in the following models: a) in vivo carrageenin-induced rat paw edema; protein-induced paw edema; arachidonic acid-induced ear edema; passive cutaneous anaphylaxis; histamine-induced skin reaction, and, b) in vitro arachidonic acid-induced platelet aggregation; protamine-induced degranulation; and, PAF-induced platelet aggregation. Bromelin, chymotrypsin and papain demonstrated a strong antiinflammatory potential and were highly effective in the carrageenin-induced paw edema model. The effects were strongly correlated to the applied dose. Only papain demonstrated an antiexsudative effect (protein-induced ear edema). Bromelin showed a modulatory effect with regard to the arachidonic acid metabolism. Both bromelin and papain demonstrated a strong antihistaminic effect, which may be due to an inhibition of degranulation (antianaphylactic potency). An inhibitory potency could be observed for rutosid and trypsin with regard to the degranulation of mast cells. No effects of the tested compounds were observed in the models of arachidonic acid-induced ear edema and PAF-induced platelet aggregation. A combination of these enzymes is at an advantage to show sequential synergy in inflammatory processes.
Pineapple is native to the South American Tropics and was widely introduced elsewhere during the sixteenth and seventeenth centuries. The crop is now widely grown throughout the tropics and subtropics. The international pineapple canning industry is based on plantations in Thailand, the Philippines, Malaysia and north Sumatra as well as in Hawaii, Brazil, Taiwan, South Africa, Kenya, Ivory Coast, Mexico and Puerto Rico.
Bromelain is a sulphydral protease, derived from the stem and fruit of pineapples. Semi-purified preparations of bromelain are used in the treatment of inflammation and oedema. There is however no unequivocal proof of the absorption of the enzyme after oral administration. In this study, 125I-bromelain was administered orally to rats and blood sampled at various times. The total radioactivity, the TCA precipitable 125I-compounds and the molecular weight profile of 125I-proteins in the plasma were determined. A maximum level, equivalent to 270 ng ml−1 bromelain was found at 1 h after administration. Approximately 40 per cent of the 125I in plasma could be precipitated by 10 per cent trichloroacetic acid. Electrophoretic analysis showed one major peak of radioactivity in the plasma samples, with a molecular weight of 26-32000 daltons. This is identical to the main molecular weight fraction in the Bromelain mixture and corresponds to the molecular weight of the purified enzyme. In the 1 h plasma sample this peak contained 0.003 per cent of the administered dose per millilitre.
Delayed onset muscle soreness (DOMS) refers to the skeletal muscle pain that is experienced following eccentric exercise. The aim of the present study was to examine the effect of aspirin supplementation on DOMS after an eccentric exercise. Sixteen healthy female [age, 21.05 ± 3.7 years; body mass index (BMI), 24.03 ± 0.8 kg/m2; (mean ± SD)] participated as subjects in this study. The subjects were assigned to either an experimental (200 mg of aspirin; n=8) or a placebo group (Same dosage of lactose; n=8) using a double-blind research design. Knee range of motion (ROM), perceived pain, thigh circumference and serum activity of the enzyme creatine kinase (CK) were taken before, immediately, 24 and 48 hours after the eccentric exercise. No differences among groups were observed for thigh circumference and ROM before, immediately, 24 and 48 hours after the eccentric exercise. Serum CK levels and pain increased (P
Crude purified bromelain extracts were obtained from 0.26% protein pineapple juice using sequential batch membrane processing systems which included microfiltration (MF) and ultrafiltration (UF) followed by ammonium sulfate extraction, ultracentrifugation and freeze drying. The membrane treatments (with an 8 μm mineral MF and a 10000 molecular weight cut-off (MWCO) organic UF membranes), combined with 60% ammonium sulfate extraction resulted in 0.75–0.8% protein concentration, with 99% protein rejection. A 70% ammonium saturation and ultracentrifugation process (27 000 × g at 2–3 ° C), prior to freeze drying, were used in the last step to remove the residual non-protein constituents. These processes achieved low-moisture freeze-dried, and light-colored extracts, free of non-protein constituents and which accounted for about 50% yielded extracts containing 98% protein. The extracts assayed for bromelain and proteolytic activity resulted in almost 100% potential recovered, at completion. However, bromelain and proteolytic activity decay during the processes described above is essentially caused by losses through adsorption on the UF membrane relative to the level of concentration reached.
In 2004 an estimated 17.1 million people died from cardiovascular diseases (CVDs) worldwide, representing 29% of all global deaths. According to the American Heart Association, heart disease and stroke are the main cause of death and disability among people with type 2 diabetes. Additional safe and effective approaches are needed for the prevention and management of CVDs which may include nutritional supplements.
To identify the potential of bromelain (a food supplement) on the risk factors associated with CVDs.
An electronic and manual search was conducted during November 2009 to March 2010. The databases searched included: Ovid MEDLINE; All EBM Reviews-Cochrane Database of Systematic Reviews (Cochrane DSR), American College of Physicians (ACP) Journal Club, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CCTR), Cochrane Methodology Register (CMR), Health Technology Assessment (HTA) and National Health Service Economic Evaluation Database (NHSEED); Allied and Complementary Medicine (AMED); British Nursing Index and Archive; EMBASE; Health Management Information Consortium (HMIC); Science Direct and Electronic Thesis Online Services (ETHOS). Only papers in the English language were included.
Randomised controlled trials (RCTs), human studies, animal studies and experimental studies related to bromelain for CVDs. Data extraction and analysis: The quality assessment of all the selected studies was conducted by the authors. Data from 3 animal trials and 3 human trials were included in the review. Data collected included: type of trial, drug dosage, duration, outcome measures, characteristics of bromelain used, significance of results and conclusion.
Out of 223 papers retrieved, 6 papers met the inclusion criteria and could be included in the review. These comprised of 3 animal and 3 human trials, each of which investigated the use of bromelain for CVDs. Results suggested that bromelain could be used for treating acute thrombophlebitis, as it decreases aggregation of blood platelets, has a cardio-protective effect, ameliorates rejection-induced arterial wall remodelling, prevents thrombin-induced human platelet aggregation as well as reduces thrombus formation.
No substantive study of bromelain and clinical CVDs has been carried out in human populations. Only a few studies on bromelain and CVDs were published from 1948 to 2010. This may be an area worthy to be explored in future CVDs research.
Associative evidence from observational and intervention studies in human subjects shows that a diet including plant foods (particularly fruit and vegetables rich in antioxidants) conveys health benefits. There is no evidence that any particular nutrient or class of bioactive substances makes a special contribution to these benefits. Flavonoids occur naturally in fruits, vegetables and beverages such as tea and wine. Quercetin is the major flavonoid which belongs to the class called flavonols. Quercetin is found in many common foods including apples, tea, onions, nuts, berries, cauliflower, cabbage and many other foods. Quercetin provides many health promoting benefits, including improvement of cardiovascular health, eye diseases, allergic disorders, arthritis, reducing risk for cancers and many more. The main aim of this review is to obtain a further understanding of the reported beneficial health effects of Quercetin, its pharmacological effects, clinical application and also to evaluate its safety.
The proteolytic enzyme, bromelain, reportedly has therapeutic effects in the treatment of inflammation and soft tissue injuries. We tested the hypothesis that bromelain attenuates skeletal muscle injury induced by lengthening contractions. The left extensor digitorum longus (EDL) muscle of anesthetized hamsters was injured using a motorized foot pedal which repeatedly flexed/extended the foot through a range of 125 degrees. The EDL muscle was electrically stimulated for 400 ms during plantarflexion. Animals were assigned randomly to either a 0-d group (evaluated 3-h post-injury) or to untreated (UT) or bromelain-treated (T) groups, evaluated 3, 7, or 14 d post-injury. Following injury, T received 5 mg.kg-1 b.w. of bromelain, twice daily. Maximum isometric tetanic force (Po) was measured in vitro, then muscles were fixed, sectioned, and examined for evidence of fiber damage. The Po of injured muscles from T were higher than Po of injured muscles from UT at 3 (18.7 +/- 0.4 vs 16.5 +/- N.cm-2 and 14 d (20.5 +/- 0.6 vs 18.2 +/- 0.6 N.cm-2) (P less than 0.05), but not 7 d (19.5 +/-0.7 vs 17.7 +/- 0.8 N.cm-2). The Po of UT injured muscles were significantly lower than Po of contralateral control muscles at all time periods. Po of injured muscles from T were lower than Po from control muscles at 3 and 7 d (P less than 0.05), but not 14 d. The number of intact fibers of 3-d UT injured muscles was lower than the number of intact fibers in control muscles (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
After a short description of the uses of pineapple as folk medicine by the natives of the tropics, the more important new pharmaceutical applications of bromelain, reported between 1975 and 1978, are presented. Although the exact chemical structure of all active components of bromelain is not fully determined, this substance has shown distinct pharmacological promise. Its properties include: (1) interference with growth of malignant cells; (2) inhibition of platelet aggregation; (3) fibrinolytic activity; (4) anti-inflammatory action; (5) skin debridement properties. These biological functions of bromelain, a non-toxic compound, have therapeutic values in modulating: (a) tumor growth; (b) blood coagulation; (c) inflammatory changes; (d) debridement of third degree burns; (e) enhancement of absorption of drugs. The mechanism of action of bromelain affecting these varied biological effects relates in part to its modulation of the arachidonate cascade.
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.
The absorption of the proteolytic enzyme bromelain was investigated in adult rats. Bromelain was labelled radioactively with 125-Iodine and intraduodenally applied. During the observation time of 6 hours blood- and lymphsamples were collected and their radioactivity measured. By radiochromatography high molecular protein could be separated from low molecular protein fragments. By means of a rabbit-anti-bromelainserum bromelain could be identified in the agar-double diffusion technique. Results show that adult rats can absorb bromelain up to 40% in a high molecular form. This observation explains the increased proteolytic activity in serum after oral application as well as the clinical effect concerning the treatment of edema or hematoma.
Aspirin is a promising antithrombogenic agent. It inhibits the generation of thromboxane A(2) by acetylating platelet cyclo-oxygenase. Aspirin also inhibits vessel wall production of PGI(2) which is an inhibitor of platelet aggregation, and therefore is potentially thrombotic. To investigate these two opposing effects we studied the effects of aspirin upon fibrin accretion onto experimentally induced venous thrombi in rabbits and on the PGI(2)-like activity of vessel wall using the thrombin-induced [(14)C]serotonin release assay. A 200-mg/kg dose of aspirin significantly augmented thrombus size when compared to (a) sodium salicylate administered in equal doses, (b) aspirin in a 10-mg/kg dose or (c) controls (P < 0.001). A 200-mg/kg dose of aspirin totally inhibited vessel wall PGI(2)-like activity whereas aspirin in a 10-mg/kg dose produced less inhibition, and 200 mg/kg sodium salicylate had no effect. Local instillation of tranylcypromine, an inhibitor of PGI(2) formation, also significantly augmented thrombus size compared to saline-treated controls and totally inhibited the production of PGI(2)-like activity. The thrombogenic effect of high dose aspirin was lost if an interval of 2.5 h or longer elapsed between vessel damage and drug administration, indicating that in contrast to the platelet, the effect of aspirin on vessel wall prostaglandin synthesis is relatively short-lived. It is concluded that aspirin, in doses higher than those used clinically, can augment experimental thrombosis, presumably by inhibiting the synthesis of vessel wall PGI(2).
Isolation and characterization of the platelet aggregation inhibitory factor of bromelain have been presented in this study. Commercial bromelain consists of 3 major components as demonstrated by discontinuous sodium chloride gradient chromatography through carbixymethyl-sephadex column. Fraction I constituted approximately 19% of the total fraction. This fraction had no proteolytic activity or platelet aggregation inhibiting activity, but showed peroxidatic activity. Fraction II and III, which constituted the remainder of the fraction eluted with 135 mM and 800 mM NaCl concentrations, respectively, showed both proteolytic and inhibition of platelet aggregation, but no peroxidatic activity. Immunoelectrophoresis and polyacrylamide electrophoresis showed fraction I with beta-mobility while fraction II and III demonstrated gamma-mobility. It is suggested that the proteolytic activity is associated with the inhibition of platelet aggregation, since oxidation of fractions II and III with sodium tetrathionate abolished both activities. The mechanism of inhibition of platelet aggregation by bromelain is presently unknown but may involve its influence on the prostaglandin synthetic pathway of platelets.
The effects of prostaglandins E1 and E2 (PGE1 and PGE2) on the aggregation and release reaction induced in human platelets by ADP have been investigated. Measurements of cyclic-AMP content in platelet-rich plasma (PRP) were made concurrently. Although both PGE1 and PGE2 independently increased platelet cyclic-AMP and inhibited first-phase ADP-induced aggregation (order of potency, PGE1 > PGE2), the effect of a fixed concentration of PGE2 in the presence of PGE1 varied. At low PGE1 concentrations the effects were additive, but at higher PGE1 concentrations PGE2 lowered the efficacy of PGE1. These results suggest that PGE2 may be a "partial agonist" of PGE1. PGE2 enhanced and PGE1 inhibited the second phase of ADP-induced aggregation and the release of serotonin by a mechanism which appeared to be independent of cyclic-AMP content. A mixture of the two prostaglandins produced responses intermediate between those observed with each prostaglandin independently. Binding of PGE1-3H to platelets was demonstrated in PRP and in concentrated platelet suspensions. PGE1 and PGE2 inhibited binding in a similar manner. It is proposed that PGE1 and PGE2 compete for a common receptor on the platelet membrane.