Article

Bromelain: A Literature Review and Discussion of its Therapeutic Applications

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Abstract

First introduced as a therapeutic compound in 1957, bromelain's actions include: (1) inhibition of platelet aggregation; (2) fibrinolytic activity; (3) anti-inflammatory action; (4) anti-tumor action; (5) modulation of cytokines and immunity; (6) skin debridement properties; (7) enhanced absorption of other drugs; (8) mucolytic properties; (9) digestive assistance; (10) enhanced wound healing; and (11) cardiovascular and circulatory improvement. Bromelain is well absorbed orally and available evidence indicates that it's therapeutic effects are enhanced with higher doses. Although all of its mechanisms of action are still not completely resolved, it has been demonstrated to be a safe and effective supplement. (Alt Med Rev 1996;1(4):243-257)

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... Udowodniono, że bromelina, wpływając na wszystkie wymienione wyżej szlaki, wykazuje działanie antysekrecyjne. Dzięki właściwościom proteolitycznym stosowano ją skutecznie jako enzym trawienny u pacjentów po pankreatektomii, w niewydolności zewnątrzwydzielniczej trzustki oraz w zaburzeniach jelitowych (20) jako skuteczny zamiennik pepsyny i trypsyny w przypadku ich niedoboru (23) . Ponadto połączenie żółci, pankreatyny i bromeliny okazało się skuteczne w ograniczeniu wydalania smolistych stolców u chorych z niewydolnością zewnątrzwydzielniczą trzustki, a także zmniejszało dolegliwości bólowe, wzdęcia i częstość wypróżnień. ...
... Ogranicza tworzenie się fibryny przez zmniejszenie ilości produktów pośrednich kaskady krzepnięcia, co oprócz działania przeciwzapalnego dodatkowo nadaje jej właściwości przeciwzakrzepowe (22) . Wpływ bromeliny obniżający stężenia bradykininy oraz fibryny skutkuje znacznym zmniejszeniem bólu i obrzęku zapalnego, jak również zwiększa napływ krwi do miejsca zranienia (23) . Bromelina hamuje także agregację płytek krwi (22) aktywowaną przez ADP (26) , a dzięki zdolności do stymulacji przekształcania plazminogenu w plazminę prowadzi do nasilenia fibrynolizy (22) . ...
... It was demonstrated that bromelain has antisecretory activity due to its effects on all the above mentioned pathways. Due to its proteolytic activity, the compound was successfully used as a digestive enzyme in patients after pancreatectomy, in pancreatic exocrine insufficiency and intestinal disorders (20) to replace pepsin and trypsin in the case of their deficiency (23) . Furthermore, a combination of bile, pancreatine and bromelain proved effective in reducing the passage of tarry stools in patients with pancreatic exocrine insufficiency as well as reducing pain, flatulence and the frequency of bowel movement. ...
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Pineapple is one of the most popular tropical fruit and an indispensable part of many people's diet. It was brought to Europe in 1493 by Christopher Columbus. The fruit has been valued for years for its unique taste and richness in nutrients, such as micro- and macronutrients, dietary fibre and a variety of vitamins. Pineapple is low in calories, but rich in nutrients; therefore, it is often included in a weight-watcher menu. Frequent consumption of pineapple almost completely covers the recommended daily intake of vitamin C, manganese and copper. Phytochemical analysis of pineapple leaf extract revealed the presence of alkaloids, flavonoids, saponins and tannins, all of which are said to be hypoglycaemic and analgesic. Studies on bromelain, pineapple's most complex bioactive compound, demonstrated its antioxidant, anti-inflammatory, digestion-enhancing and cardioprotective effects. The multitude of potential uses of bromelain combined with the effects of many other nutrients found in a pineapple, allow us to appreciate not only its unquestionable taste, but also other benefits of this fruit. Pineapple is no exception and throughout the years many myths about its beneficial and harmful properties have emerged. Fortunately, most of these have never been confirmed scientifically and pineapples have no known negative impact on the human body. The aim of this study was to present the nutritional value of pineapple and its role in medical treatment.
... Bromelain is the general name for a family of sulfhydryl proteolytic enzymes obtained from Ananas comosus, the pineapple plant. (8) At present, bromelain is marketed as a dietary supplement and is available to the community in health food stores and pharmacies in Europe and the US. In China, it is approved as a registered drug and widely used clinically for reduction of inflammation, specifically thrombophlebitis. ...
... This was because bromelain tends to act as a digestive enzyme and its therapeutic benefit may be diminished if taken with food. (8) The 1,050 mg dosage was chosen based on a review by Kelly (8) who suggested that the optimum effect of bromelain occurs starting at a dose of 750-1,000 mg/d for a longer period of time. ...
... This was because bromelain tends to act as a digestive enzyme and its therapeutic benefit may be diminished if taken with food. (8) The 1,050 mg dosage was chosen based on a review by Kelly (8) who suggested that the optimum effect of bromelain occurs starting at a dose of 750-1,000 mg/d for a longer period of time. ...
Article
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.
... Another cysteine protease that is suggested to possess antitumour activity is bromelain, extracted from the waste of pineapple Ananas comosus. Bromelain is represented by the group of proteolytic enzymes located in different parts of the pineapple: stem bromelain (EC 3.4.22.32), and other forms of bromelain are present in fruit juice, peel, core, crown and leaves [40]. Stem bromelain is commercially available and is most often used in studies and referred to as "bromelain". ...
... They influence tumour progression in several directions (Fig. 1). Firstly, they decrease the amounts of surface proteins and adhesion molecules on host CD4+, CD8+ T-cells and macrophages through proteolytic cleavage [40,44]. Secondly, papain and bromelain are known to bind irreversibly to antiproteases such as α2-macroglobulin or α1-antitrypsin [45], which stimulates the synthesis of more antiproteases by macrophages, which in turn inactivates tumour proteases essential for tumour development and metastasis, such as cathepsins [46]. ...
... Thirdly, papain and bromelain may decrease the amounts of cytokines, e.g., TNF-β, thus promoting the immunosuppression of the host and providing tumour escape. Plant protease-antiprotease complexes bind to cytokines such as IL-1, IL-6, IFN-γ and TNF-β and lead them out from the tumour, providing an antitumour and anti-inflammatory effect ( Fig. 1) [40]. In addition, tumours block the immune system factors which allow the tumour cells to protect themselves from being recognized by antibodies and immune cells. ...
Article
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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.
... [13][14][15] Efek terapi dari enzim bromelain yaitu dapat meningkatkan aktivitas fibrinolitik serum dengan cara mengubah plasminogen menjadi plasmin yang dapat berfungsi sebagai pemecah gumpalan darah yang menghambat aliran darah, mengurangi kadar fibrinogen plasma dan menurunkan kadar bradikinin yang menghasilkan penurunan permeabilitas pembuluh darah sehingga mengurangi edema dan nyeri. 16,17 Selain itu dapat juga dengan mediasi tingkat prostaglandin (dengan mengurangi kadar PGE2 dan tromboksan A2), serta dapat meningkatkan PGI2 untuk memodulasi sitokin inflamasi (TNF dan IL-1). Vitamin C berkhasiat sebagai antioksidan dapat menangkal radikal bebas. ...
... 15 Dengan demikian, efek anti-inflamasi dari bromelain dan antioksidan dari vitamin C diperkirakan dapat berperan mengurangi edema dan menurunkan tingkat nyeri yang dirasakan penderita. [15][16][17] Berdasarkan hasil penelitian ini, pemberian sari buah nanas setelah induksi asam mefenamat memperlihatkan efek percepatan proses penyembuhan jaringan lambung yang mengalami peradangan dan kerusakan akibat efek obat asam mefenamat. ...
Article
Inflammation of the stomach can be caused by various factors, including the use of non-steroidal anti-inflammatory (NSAID) drugs such as mefenamic acid. Pineapple (Ananas comosus (L.) merr) is a herbal remedy used to treat gastritis. Pineapple contains several nutrients such as vitamin C and bromelain enzyme that are efficacious as anti-inflammatory and antioxidant. This study aimed to determine histopathological features of the gastric of wistar rats (Rattus norvegicus) given pineapple juice after induction of mefenamic acid. This was an experimental study using 20 wistar rats divided into four groups; each group consisted of five rats. Group I (negative control) was given no treatment. Group II was induced with mefenamic acid 23.25 mg/day single dose for seven days. Group III was induced with mefenamic acid 23.25 mg/day single dose for seven days then was given no treatment during the next seven days. Group IV was induced with mefenamic acid 23.25 mg/day single dose for seven days then was administered with pineapple juice over the next seven days. Rats in group I and II were terminated on day-8 while those in groups III and IV were terminated on day-15. The results showed that the gastric tissue of rats in group IV had less inflammatory cells but more regenerating cells than those in group II and III. Conclusion: Histopathological features of the gaster of wistar rats treated with pineapple juice after the induction of mefenamic acid showed milder signs of acute gastritis and more prominent of cell regeneration/tissue recovery than those given no pineapple juice.Keywords: gastritis, mefenamic acid, pineapple Abstrak: Peradangan lambung dapat disebabkan oleh berbagai faktor, diantaranya penggunaan obat golongan anti-inflamasi non steroidal (AINS) seperti asam mefenamat. Buah nanas (Ananas comosus (L.) merr) merupakan salah satu obat herbal yang digunakan untuk mengatasi gastritis. Buah nanas mengandung beberapa bahan nutrisi seperti enzim bromelain dan vitamin C yang berkhasiat sebagai anti inflamasi dan antioksidan. Penelitian ini bertujuan untuk mengetahui gambaran histopatologik lambung tikus Wistar (Rattus norvegicus) yang diberikan sari buah nanas setelah induksi asam mefenamat. Jenis penelitian ialah eksperimental menggunakan subyek 20 ekor tikus wistar yang dibagi dalam empat kelompok; setiap kelompok terdiri atas lima ekor tikus. Kelompok I (kontrol negatif) tidak diberi perlakuan. Kelompok II diberikan asam mefenamat 23.25 mg/hari dosis tunggal selama tujuh hari. Kelompok III diberikan asam mefenamat 23.25 mg/hari dosis tunggal selama tujuh hari dan tidak diberikan perlakuan selama tujuh hari berikutnya. Kelompok IV diberikan asam mefenamat 23.25 mg/hari dosis tunggal selama tujuh hari dan diberikan sari buah nanas selama tujuh hari berikutnya. Tikus pada kelompok I dan II diterminasi pada hari ke-8 dan kelompok III dan IV pada hari ke-15. Hasil penelitian menunjukkan gambaran histopatologik lambung tikus wistar berupa infiltrasi sel-sel radang yang lebih sedikit serta sel-sel regenerasi yang lebih aktif dan banyak pada kelompok IV jika dibandingkan kelompok II dan III. Simpulan: Gambaran histopatologik lambung tikus wistar yang diinduksi sari buah nanas setelah diberi asam mefenamat menunjukkan tanda-tanda gastritis akut yang lebih ringan dan regenerasi sel/pemulihan jaringan yang lebih menonjol dibandingkan dengan yang tidak diberi sari buah nanas. Kata kunci: gastritis, asam mefenamat, nanas
... 6 This bromelain is said to have anti-inflammatory, bactericidal, and bacteriostatic properties. 7 Numerous studies reveal that bromelain has a potent deproteinization effect similar to that of papain, hence used for the study. 8 My study aims to compare the caries removal efficacy of three minimally invasive techniques using the chemomechanical method-Bromelain gel, smart burs, and ART-and to analyze residual dentin under stereomicroscopy and dentin microhardness using Vickers hardness test. ...
... 13 It is said that bromelain activates collagenase in living tissue which then attacks the denatured collagen. 7 This produces a distinction between living and dead tissue. Bromelain toxicity levels are very low with LD 50 >10 g/ kg, and it has no carcinogenic potential. ...
Article
Aim: This study aims to compare the caries removal efficacy of three minimally invasive techniques and to analyze qualitatively under stereomicroscopy and quantitatively using Vickers hardness test. Materials and methods: Thirty non-carious anterior primary teeth were selected and subjected to demineralization and the same was confirmed using RadioVisioGraphy (RVG). Samples were divided into three groups: Bromelain gel, smart bur, and atraumatic restorative technique (ART). Caries removal was carried out for a time period of 2 minutes. The remaining demineralized dentin was measured using stereomicroscopy. Random dentin blocks were prepared and a microhardness test was conducted. Statistical analysis: Data were subjected to statistical analysis by one-way analysis of variance (ANOVA) test. Results: Stereomicroscopic analysis revealed bromelain gel and smart burs to be superior to ART. Bromelain gel was found to have comparable microhardness levels as healthy dentin. Statistically significant (p < 0.001) results were obtained. Conclusion: In terms of caries removal and microhardness, bromelain gel was highly efficient when compared to other groups. Clinical significance: Fear and anxiety of children and parents about conventional drills led to the emerging trends of minimally invasive restorative dentistry. This research indicated the use of bromelain gel and smart bur in the process of caries removal and that bromelain was more efficient when compared to other groups. How to cite this article: Abinaya R, Nagar P, Urs Pallavi, et al. Comparing the Efficacy of Three Minimally Invasive Techniques on Demineralized Dentin in Primary Teeth and Evaluating Its Residual Dentin and Microhardness Levels: An In Vitro Study. Int J Clin Pediatr Dent 2020;13(6):585-589.
... It also reduces prekallikrein (PK), and thus, inhibits the generation of bradykinin at the site of inflammation. As a result, it reduces edema and pain, while increasing circulation at the injury site [85]. ...
... As a result, they claimed a quicker reduction rate of edema and contusion in subjects who took bromelain compared with cases where a placebo was used [88][89][90]. Severe, full-thickness wounds are healed more quickly with timely debridement and removal of eschar to decrease wound bioburden [84,85]. For burn wounds, effective eradication of the eschar within 72 h is recommended [90]. ...
Article
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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.
... 34 Bromelain also denatures membrane proteins by forming complex compounds with them, disrupting their chemical structure, causing protein coagulation, and cell membrane lysis. [35][36][37][38][39] Bromelain remains a promising antibacterial candidate against oral pathogens. Further stability and sensory studies of the enzymes in this extract are needed. ...
... It has anti-inflammatory, antitumor, antibacterial, and immune modulating properties. [37][38][39][40] Bromelain has the potential to reduce plaque formation in the teeth. 14 This study showed that bromelain also has antibacterial activity against E. faecalis. ...
Article
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strong>Background: Enterococcus faecalis is the frequent cause of oral infections, such as periodontitis, infected root canals, and peri-radicular abscesses. Pineapple ( Ananas comosus ) fruit contains bromelain, one of proteolytic enzymes associated with several health benefits. Bromelain has been shown to promote healthy digestion, stimulate the immune system, improve cardiovascular conditions, and accelerate wound healing. Bromelain compounds possess anti-inflammatory and anticancer properties and exhibit antibacterial activity. Objective: To analyze the enzymatic activity of bromelain extracted from pineapple hump and investigate the antibacterial effect of bromelain against E. faecalis. Methods: Pineapple hump was dried and extracted with maceration technique. Further purification was obtained by ammonium sulfate fractionation, dialysis and ion exchange chromatography. Minimum inhibitory concentration (MIC) tests using diffusion and dilution techniques tested the antibacterial activity of the bromelain extract on E. faecalis. A one-way analysis of variance (ANOVA) test analyzed the significance of the differences in the E. faecalis inhibition zones after treatment with a range of bromelain extract concentrations. Differences were considered statistically significant if p < 0.05. Results: The specific activity of bromelain in the crude extract was 62.89 U/mg. Furthermore, bromelain activity using ammonium sulfate fractionation was 50.99 U/mg, dialysis was 54.59 U/mg, and ion exchange chromatography was 152.38 U/mg. The bromelain extract showed effective inhibitory and bactericidal activity against E. faecalis. The results of the inhibition test using a bromelain extract purified by ion exchange chromatography demonstrated that a concentration as small as 12.5% was effective in inhibiting the growth of E. faecalis (p < 0.05). Conclusion: The highest enzymatic activity of bromelain was found after purification with ion exchange chromatography. Bromelain exerted an antibacterial effect against a potent endodontic pathogen, but further studies are needed to explore this effect.
... Different herbal drugs have been proposed for the treatment of ARS [26]. Recent years sinusitis has been taken into great account, therefore the formulations are developed and researches have been done and accordingly, it has been observed that the formulation used are of single herb or poly herbal formulation [27]. ...
... Recent years sinusitis has been taken into great account, therefore the formulations are developed and researches have been done and accordingly, it has been observed that the formulation used are of single herb or poly herbal formulation [27]. ...
... Bromelain's action is in part a result of inhibiting the generation of bradykinin at the infl ammatory site via depletion of the plasma kallikrein system, as well as limiting the formation of fi brin by reduction of clotting cascade intermediates. These actions result in significant reduction in pain and oedema, as well as enhanced circulation to the injured site (Kelly, 1996). Bromelain has been shown to exert benefi cial effects, some of which are antiinfl ammatory in acute injuries and prevent platelet aggregation at doses as low as 160 mg/day (Blonstein, 1960). ...
... Alternatively, it may be attributed to the fact that bromelain increases the expression of PGI 2 and PAF through a modulation of the cytokine system. This in turn results in an increase proliferation of tenoblasts and collagen synthesis (Kelly, 1996). The increased population of tenocytes thus generates ROS in response to cytokines and growth factors in addition to the fact that the pro-proliferative action of growth factors may be mediated through H 2 O 2 production (Banes et al., 1995;Sundaresan et al., 1995). ...
Article
Bromelain, an enzyme extracted from the stem of the pineapple plant has been proposed as a treatment for reducing pain and swelling following acute muscle injuries but studies are yet to be done on its effect on tendon healing. This study therefore investigated the effects of bromelain on tenocyte proliferation and the tendon malondialdehyde (MDA) level in the early stage of healing in a crush injury to the Achilles tendon of Sprague-Dawley rats. Twenty four male rats were divided randomly into three groups; groups 2 and 3 had induced crush injury to the left Achilles tendon. Group 1; nil injury and nil treatment, Group 2; nil treatment, Group 3; oral bromelain treatment. Bromelain was given at a dosage of 7 mg/kg body weight daily over the fi rst 14 days post-injury. On day 15 post injury, the animals were killed and the tendons excised and processed for histological study and MDA assay. The results showed a signifi cant increase in the tenocyte population in the bromelain group; p < 0.05. There was, however, no signifi cant difference in the MDA level. Conclusion: Based on this study, 600 GDU bromelain given once daily in acute tendon injury at a dosage of 7 mg/kg promoted healing by stimulating tenocyte proliferation.
... Due to its proteolytic activity, bromelain has been extensively used as active for therapeutic applications in several animal models [4][5][6]. A wide range of therapeutic benefits have been attributed to bromelain due to its action as therapeutic agent in inflammation, autoimmunity and allergy, as well as the reversible inhibition of platelet aggregation, bronchitis relief, improved recovery after surgical traumas, and enhanced absorption of drugs, particularly antibiotics [7][8][9][10]. Enzymatic debridement of necrotic tissues from ulcers, burn wounds and frostbite eschar, as well as antiproliferative and antimetastatic effects on tumor models have been also presented in Refs. ...
Article
This work aimed the incorporation of the enzyme bromelain from pineapple peel into dermatological bases for potential therapeutic application. The enzyme was incorporated into Lanette cream and lotion, as well as Carbopol gel and Chemyunion® cream and lotion, at a concentration of 0.5% (w/w). These bases were subjected to centrifugation test and accelerated stability test during 90 days at 25 °C (with and without sunlight), 37 °C and 4 °C, in order to evaluate bromelain stability in dermatological bases. Total protein content and enzymatic activity were measured. The ases were stable as its organoleptic characteristics (appearance, color, smell and sensitivity to touch) only when kept at 4 ºC with activity remaining 95.5%, 84,9%, 77.7%, 73.8% and 72.3%, after 90 days of testing in Carbopol gel, Lanette and Chemyunion® cream, and Lanette and Chemyunion® lotion, respectively. Based on the results, it was possible to incorporate bromelain into dermatological bases, and the activity was well preserved when these bases were kept in refrigerator at 4 ºC.
... Phytopharmaka und sekundäre Pflanzenstoffe werden in der medikamentösen Therapie und Gesundheitsvorsorge zunehmend und mit positiver Beurteilung angewendet (12, 15,27,39,62 ...
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Bromelain, a plant-derived proteolytic enzyme, is commercially available and has been approved as a pharmaceutical preparation. Bromelain is mainly prescribed for the treatment and prevention of inflammatory, posttraumatic or postoperative swelling. The mode of action has been investigated in cell-culture and animal experiments. In controlled clinical studies in humans, orally-administered Bromelain has proven its pharmaceutical efficacy by significantly reducing soft-tissue edema in the above-mentioned conditions. Therefore, Bromelain is also of interest for sports medicine and sports traumatology. Oral treatment with Bromelain has few and only transient and mild side-effects and may therefore be an effective alternative for non-steroidal anti-inflammatory drugs in the treatment of posttraumatic edema and swelling. This review summarizes present knowledge regarding the mode of action of Bromelain and gives an overview about its practical applications from a sports-medical point of view.
... 8 Moreover, granulocytes reacted to the same compound by forming a reactive oxygen radical with the antimicrobial effect. 7 There are more than thousands of wellknown phytochemicals, and two of the most commonly found in pineapple are polyphenol antioxidants such as flavonoids and Vitamin C. 9 These phenols have the ability to denatures the protein. Phenol was also lipophilic that attracted to lipid molecules contained in the cell membranes. ...
Article
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Introduction: Staphylococcus aureus is one of the important medical pathogens which have been recognised for many years as a remedyfor a wide case of oral infections. Nowadays, the use of herbal remedy for reducing bacteria in the oral cavity has been implemented widely due to thefewer side effects. Therefore, researchershave been findingwaysto use pineapple in dentistry to prevent many cases of oral diseases. The purpose of this study was to prove that pineapple extract indifferent concentration had the potential as an antibacterial agent towards Staphylococcus aureus. Methods: The study was an experimental laboratory conducted by determining the minimum inhibitory concentration of pineapple (Ananas comosus) with thetwo-fold serial dilution methods. Results:The The Minimum Inhibitory Concentration (MIC) of the pineapple extract was 1.56%-0.78%. Conclusion: The pineapple extract had anantibacterial effect towards Staphylococcus aureus due to the bromelain compound and its phytochemical factor such as Vitamin C and flavonoid.
... Bromelain proteases from pineapple extracts (Fruit bromelain) are clinically used as anti-inflammatory agents (Ammon, 2002;Darshan and Doreswamy, 2004;Lemay et al., 2004) for colonic inflammation, chronic pain, rheumatoid arthritis, soft tissue injuries, and asthma (Izaka et al., 1972;Cooreman et al., 1976;Taussig and Batkin, 1988;Kelly, 1996;Maurer, 2001;Jaber, 2002;Hale et al., 2005). Similar folding and disulfide bond connectivity were found to be shared in Bromelain inhibitor VI from pineapple stem (Stem bromelain, BI-VI) with the Bowman-Birk trypsin/chymotrypsin inhibitor from soybean (BBI-I) (Hatano et al., 1996). ...
Article
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Plants are known to have many secondary metabolites and phytochemical compounds which are highly explored at biochemical and molecular genetics level and exploited enormously in the human health care sector. However, there are other less explored small molecular weight proteins, which inhibit proteases/proteinases. Plants are good sources of protease inhibitors (PIs) which protect them against diseases, insects, pests, and herbivores. In the past, proteinaceous PIs were considered primarily as protein-degrading enzymes. Nevertheless, this view has significantly changed and PIs are now treated as very important signaling molecules in many biological activities such as inflammation, apoptosis, blood clotting and hormone processing. In recent years, PIs have been examined extensively as therapeutic agents, primarily to deal with various human cancers. Interestingly, many plant-based PIs are also found to be effective against cardiovascular diseases, osteoporosis, inflammatory diseases and neurological disorders. Several plant PIs are under further evaluation in in vitro clinical trials. Among all types of PIs, Bowman-Birk inhibitors (BBI) have been studied extensively in the treatment of many diseases, especially in the field of cancer prevention. So far, crops such as beans, potatoes, barley, squash, millet, wheat, buckwheat, groundnut, chickpea, pigeonpea, corn, and pineapple have been identified as good sources of PIs. The PI content of such foods has a significant influence on human health disorders, particularly in the regions where people mostly depend on these kind of foods. These natural PIs vary in concentration, protease specificity, heat stability, and sometimes several PIs may be present in the same species or tissue. However, it is important to carry out individual studies to identify the potential effects of each PI on human health. PIs in plants make them incredible sources to determine novel PIs with specific pharmacological and therapeutic effects due to their peculiarity and superabundance.
... It also contains escharase (a non proteolytic component), several protease inhibitors, glycoproteins, carbohydrates and organically bound calcium (Bhattacharyya, 2008). A wide range of therapeutic benefits has been reported for bromelain, such as improving cardiovascular and circulatory diseases (Nieper, 1978), acceleration of wound healing (Kelly, 1996) , reversible inhibition of platelet aggregation, anti-edema (MacKay et al., 2003), antithrombotic and fibrinolytic activity (Errasti et al., 2016). As an adjunct in cancer therapy, bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity of monocytes against tumor cells and by inducing the cytokines production (Bhattacharyya, 2008 ...
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This study aimed to assess the antioxidant activity of the pineapple crude juice extracted from the whole fruit, and its effect in stimulating thyroid hormones synthesis in hypothyroid rats, as well as anticipating the concomitant hyperlipidemia. Male Swiss albino rats were divided into: normal (euthyroid) controls; normal rats orally administrated with pineapple juice (0.75 ml/100g body weight) for 8 consecutive weeks; hypothyroid rats administrated methimazole (0.02% w/v) in drinking water for 15 days; and treated hypothyroid rats orally administrated with methimazole then pineapple juice for 8 weeks. In vitro antioxidant studies demonstrated that pineapple juice has high scavenging activity for nitric oxide and α,α2-diphenyl-β-picrylhydrazyl radicals, a high ferric reducing antioxidant power and an inhibitory effect on lipid peroxidation. Supplementation of euthyroid rats with pineapple juice for 8 weeks reduced the body weight and elevated serum T3 and T4 levels, compared to normal controls. While, supplementing hypothyroid rats with the pineapple juice normalized serum levels of T3, free cholesterol and its percentage of esterification, LDL-C, HDL-C, atherogenic index and LCAT activity, as well as serum, heart and hepatic MDA concentration and GPX activity. The histological examination of thyroid tissue sections of hypothyroid supplemented rats revealed an improvement in the cellular architecture of the thyroid gland epithelium lining the follicles and partial filling of the follicular lumen with colloid. Pineapple juice attenuates the excessive methimazole induced oxidative stress and consequent hyperlipidemia, also, activates the thyroid gland functions, suggesting its benefit as therapeutic supplement or as an adjunct in hypothyroidism therapy.
... Bromelain is extracted from the stem and fruit of Pineapple (Ananas comosus) plant. It prevents the propagation of inflammation by blocking pro-inflammatory metabolites used extensively to treat arthritis, trauma and other inflammatory processes (13). Medically papain and bromelain in conjunction with animal proteases like trypsin and chymotrypsin offer a wide spectrum of therapeutic effects. ...
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Background Patients undergoing fixed orthodontic therapy may have difficulty in maintaining a good oral hygiene due to the difficulty posed by the appliances in accessing such areas. This study aimed to compare anti-plaque and anti-gingivitis efficacy of dentifrice containing Papain, Bromelain, Miswak and Neem with a standard dentifrice among patient’s undergoing fixed orthodontic treatment. Material and Methods Single center, single blind, parallel arm, randomized controlled clinical trial with an allocation ratio of 1:1 was conducted. Evaluation of plaque and gingivitis was done using Williams modification of Silness and Loe Plaque Index (PI) for use in orthodontic subjects and Loe and Silness’s Gingival Index (GI) at baseline and one month. Results Inter-group comparison showed there was significantly lower mean plaque index in test (0.88 ±0.05) than in control group (1.17 ±0.05) after adjusting for the baseline plaque index (p<0.001). Similarly, there was significantly lower mean gingival index in test (0.87 ±0.04) than in control group (1.14 ±0.04) after adjusting for the baseline gingival index (p<0.001). Conclusions The efficacy of the test dentifrice in limiting plaque and gingivitis suggests that it can be used as a home based adjunct to clinical therapy in orthodontic patients. Key words:Bromelain, gingivitis, miswak, neem, papain, plaque.
... Bromelain is a collective name for all proteases, sulfhydryl proteolytic enzymes belonging to the Bromeliaceae family [1]; it is one of the protease enzymes found in the pineapple plant (Ananas comosus) [2]. Bromelain is present in all parts of the pineapple plant, but its characteristics depend on the source [3]. ...
... Bromelain refers to proteolytic enzyme derived from pineapple plant (Ananas comosus). Stem bromelain (EC 3.4.22.32) is the major protease present in extracts of pineapple stem while fruit bromelain (EC 3.4.22.33) is the main protease fraction present in pineapple fruit [1]. Stem bromelain is widely used in food industry; for baking processes, meat tenderization, protein hydrolysate production, as food supplement and in prevention of browning of apple juice [2]. ...
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Bromelain is a plant protease with numerous therapeutic, industrial and analytical applications. Spray drying of enzyme often leads to loss of enzymatic activity arising from thermal denaturation. Hence, the design of a suitable drying process should provide a great level of active enzyme. The present study examined the effect of operating parameters of a laboratory spray dryer on powder characteristics, so as to optimize the production of recombinant bromelain expressed in E. coli BL 21-AI. The recombinant enzyme was spray dried from maltodextrin (10 %w/v), CaCl2 (0.2 % w/v) and sodium metabisulphite (2.5 % w/v) solutions using a laboratory-scale Büchi Mini Spray dryer B-290. The process parameters investigated were: drying air inlet temperature (100-120 °C), drying air volumetric flow rate - given as % of the maximum aspiration rate (80-100 %), feed volumetric flow rate- expressed as % of the maximum pump rate (10-15 %). On the other hand, the activity of bromelain (U/ml) served as the response of the design. Outlet temperature was maintained at 50 °C. All the studied process parameters had significantly affected the characteristics of the powdered bromelain, at a 95% confidence interval. The higher values of coefficient of determination (R2 = 99.95% and adjusted R2 = 99.84%) attained, showed that there is good compliance between the experimental and the theoretical values predicted by the model. Moreover, the graphical representations of the regression equation generated suggested that the examined independent variables interacted significantly. Thus, the corroboration of reality of the optimal conditions and the validity of the model had been ascertained. Consequently, under optimized process conditions, the study had produced powdered bromelain with greater quality in terms of moisture contents, residual activity and product recovery.
... An additional advantage of plant protease is that they do not require any cofactors for their activity and hence they are preferred for industrial application (Mufti et al., 2006). Plant extracts with a higher amount of proteolytic activity have been used in traditional medicine for a long time and are directly used in the treatment of cancer (Batkin et al., 1988;Targoni et al., 1999), digestion disorders (Kelly, 1996;Mello et al., 2008), tumours (Guimaraes-Ferreira et al., 2007;Otsuki et al., 2010), swelling and immune-modulation problems (Leipner et al., 2001;Lotti, 1993;Melis, 1990;Otsuki et al., 2010). In the present study, proteases have been detected from leaves of 80 medicinally important plants belonging to 34 different families that are used for various ailments. ...
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Ethno-pharmacological relevance: The whole plant or the extracts obtained from them have long been used as medicine to treat various human diseases and disorders. Notably, those plants endowed with protease activity have been traditionally used as the agents for treating tumors, digestion disorders, swelling, blood coagulation, fibrinolysis and also for immune-modulation. Aim of the study: Proteases occupy a pivotal position in enzyme based industries. Plant proteases have been increasingly exploited for pharmaceutical, food, leather and textile processing industries. Earlier investigations have focused on the occurrence of proteases in medicinally unimportant plants. Therefore it has been aimed to study the occurrence of proteolytic enzymes from medicinally important plants establish any correlation exists between protease activity and medicinal use of individual plants. Methods: Crude extract were obtained from the leaves of 80 different medicinal plants. Tris-HCl buffer was used as the extraction buffer and the supernatants obtained were used for determination of total protein and protease activity using spectrophotometric methods. Qualitative screening for the presence of protease was carried out with agar diffusion method by incorporating the substrate. SDS-PAGE was used to analyse the isoforms of protease and for determination of relative molecular mass. Results: Relatively higher protease activities were observed in the extracts of leaves of Pongamia pinnata (Fabaceae), Wrightia tinctoria (Apocyanaceae) Acalypha indica (Euphorbiaceae), Adhatoda vasica (Acanthaceae) and Curcuma longa (Zingiberaceae). No correlation was found between the total protein content and protease activity in individual plant species. SDS-PAGE analysis indicated the presence of multiple forms of protease of higher molecular weight range in several plant species. We found a strong correlation between the protease activity and medicinal application of the plant CONCLUSION: The present study has unequivocally revealed that the leaves of medicinal plants could serve as excellent sources of proteases which could be exploited for various industrial, food and pharmaceutical applications.
... Evidence has suggested that bromelain counteracts the effects of intestinal pathogens like Escherichia coli, whose enterotoxin causes diarrhoea in pigs (Pavan et al. 2012). These effects may be attributed to the sulfhydryl proteolytic fraction, the main chemical compounds in bromelain, which also contains phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors (Kelly 1996;Pavan et al. 2012). Bromelain can be absorbed in human intestines wall without degradation and maintain its biological activity (Castell et al. 1997;Chobotova et al. 2010). ...
Article
A total of 180 crossbred pigs [(Landrace × Yorkshire) × Duroc] with an average body weight of 22.61 ± 1.23 kg were used in an 18 wk study to determine the effect of protease and bromelain in low-protein diets in grower–finisher pigs. Dietary treatments included: T1, basal diet treatment; T2, low-protein treatment; T3 (T2 + 0.2 g kg⁻¹ protease); and T4 (T2 + 0.3 g kg⁻¹ bromelain). Pigs fed protease-and bromelain-supplemented diets increased average daily gain and gain to feed ratio at week 18, dry matter and nitrogen digestibility at week 6, as well as energy digestibility at week 12, compared with low-protein diet (P < 0.05). Pigs fed T3 and T4 diets led to a trend of decreased (P < 0.05) blood urine nitrogen (BUN) and creatinine concentrations at the 12th wk. A reduction of ammonia (NH3) and hydrogen sulfide (H2 S) emission was observed in pigs fed the dietary protease and bromelain supplementation at the 6th wk (P < 0.05). There was no effect on all parameters between the protease and bromelain supplementation treatments. In conclusion, supplementation of protease and bromelain to low-protein diet enhanced growth performance, nutrient digestibility, and reduced NH3 and H2 S in growing–finishing pigs.
... Evidence has suggested that bromelain counteracts the effects of intestinal pathogens like Escherichia coli, whose enterotoxin causes diarrhoea in pigs (Pavan et al. 2012). These effects may be attributed to the sulfhydryl proteolytic fraction, the main chemical compounds in bromelain, which also contains phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors (Kelly 1996;Pavan et al. 2012). Bromelain can be absorbed in human intestines wall without degradation and maintain its biological activity (Castell et al. 1997;Chobotova et al. 2010). ...
Article
A total of 140 growing pigs [Duroc × (Yorkshire × Landrace)] with an average body weight (BW) of 24.10 ± 1.66 kg were used in a 6-wk trial to determine the effect dietary protease supplementation in different energy diets in growing pigs. Pigs were randomly allotted to one of four dietary treatments in a 2 × 2 factorial design, with 2 levels of nutrient density (low or high nutrient density) and protease (0 or 125 g protease/ton) according to their sex and BW (7 pens with 3 barrows and 2 gilts/pen). Individual pig BW and pen feed consumption were recorded at the end of sixth week to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F). Fresh fecal samples were collected at the sixth week for calculation of dry matter (DM) and nitrogen (N) digestibility. All data were subjected to the mixed procedure of SAS for a randomized complete block design with a 2 × 2 factorial arrangement. Pigs fed the high density diets increased (P < 0.05) ADG, G:F, and energy digestibility compared with the low density diets during 6 weeks. The supplementation of protease in the diet did not have significant effect on BW, ADG, and digestibility of DM and N. However, at week 6, pigs fed the diet with protease supplementation increased energy digestibility (P < 0.05). In addition, trends in increased DM digestibility and G:F) (P = 0.08, P = 0.09 respectively) were observed. With regards to blood profiles, a significant increase in the level of creatinine at the 6th week and trends in increased blood urea nitrogen (BUN) (P = 0.06) and reduction in nor-epinephrine levels (P = 0.07) were also observed. Further more, ammonia gas emission, tended (P = 0.06) to reduce in the faeces of pigs fed protease supplemented diets. In conclusion, these results suggest that supplementation of growing pigs diet with protease significantly increased energy digestibility and creatinine levels, tended to increase G:F, DM digestibility, BUN, and decreased ammonia gas emission and norepinephrine levels. Key Words: digestibility; growth performance; pigs; protease. Table. Effect of different energy diet supplementations of protease on growth performance in growing pigs, wk 0 to 6 Item Low High SEM P-value ˗ Prot + Prot ˗ Prot + Prot Density Prot Density × Prot ADG, g 692 716 735 758 20.24 0.045 0.254 0.981 ADFI, g 1573 1564 1565 1546 21.90 0.565 0.539 0.824 G:F 0.440 0.458 0.470 0.490 0.01 0.005 0.08 0.924 Item Low High SEM P-value ˗ Prot + Prot ˗ Prot + Prot Density Prot Density × Prot ADG, g 692 716 735 758 20.24 0.045 0.254 0.981 ADFI, g 1573 1564 1565 1546 21.90 0.565 0.539 0.824 G:F 0.440 0.458 0.470 0.490 0.01 0.005 0.08 0.924 Table. Effect of different energy diet supplementations of protease on growth performance in growing pigs, wk 0 to 6 Item Low High SEM P-value ˗ Prot + Prot ˗ Prot + Prot Density Prot Density × Prot ADG, g 692 716 735 758 20.24 0.045 0.254 0.981 ADFI, g 1573 1564 1565 1546 21.90 0.565 0.539 0.824 G:F 0.440 0.458 0.470 0.490 0.01 0.005 0.08 0.924 Item Low High SEM P-value ˗ Prot + Prot ˗ Prot + Prot Density Prot Density × Prot ADG, g 692 716 735 758 20.24 0.045 0.254 0.981 ADFI, g 1573 1564 1565 1546 21.90 0.565 0.539 0.824 G:F 0.440 0.458 0.470 0.490 0.01 0.005 0.08 0.924
... Proteases also have been widely used in pharmaceutical industries. Plant-based proteases with high levels of proteolytic enzymes have been traditionally used for a long time for the treatment of anti-tumorals [12,13], cancer [14,15], digestion disorders [16,17] and immune-modulation problems. Bromelain protease has been reported to prevent platelet aggregation, prevent edema and metasis due to its capacity in modifying cell structure through peptide cleavage [14]. ...
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In the past decades, the interest towards plant proteases has increased significantly. Plant proteases are widely used in environment field, food and medicine industries. Proteases such as bromelain, papain and ficin are used in various areas such as in biosensors for detection of heavy metals, meat tenderization, brewing, cancer treatment, milk-clotting, viral disorders and digestion. In this study, protease from coriander leaf (Coriandrum sativum) was evaluated for protease activity using a Bradford-protease-casein assay system. This enzyme was purified through anion exchanger using DEAE-Cellulose column and gel filtration using Agilent ZORBAX column. Its molecular weight was around 55 kDa. The specific activity of the purified protein was 45.0 units/mg protein, total activity was 2745.0 units, yield 33.2% and fold purification was 2.8. Further investigation on gene sequence should be performed in order to identify the type of protease involved.
... (13) Bromelain are considered to have a range of beneficial properties as anti-inflammatory, analgesic actions, anti-oedematous, anti-thrombotic, anti-diarrheal, antibiotics, anti-tumor, skin debridement, digestive aid, musculoskeletal injuries, reduces the blood pressure level, prevents aggregation of blood platelets, activates plasmin, supports the oxidative burst and fibrinolytic effects. (14)(15)(16)(17) In humans, bromelain has been well documented to increase blood and urine levels of antibiotics and results in higher blood and tissue levels of tetracycline and amoxicillin when they are administered concurrently with bromelain. (18) Bromelain has been successfully used as a digestive enzyme because of its wide pH range, bromelain has activity in the stomach as well as the small intestine. ...
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BACKGROUND: Bromelain is a sulfhydryl proteolytic enzyme that can hydrolyze protein, protease or peptide. Bromelain can be found in pineapple stem, fruit and core. Bromelain is composed of 212 amino acid residues with cysteine-25 forming a polypeptide chain that can hydrolyze peptide bonds by H2O. In medicine, bromelain has been developed as antibiotic, cancer drug, anti-inflammatory agent and immunomodulator. In dentistry, bromelain has potential to reduce plaque formation on the teeth and to irigate root canal. METHODS: Pineapple core was dried for 3 days to get simplicia. Then simplicia was extracted with water solvent for 24 hours. After that, the macerated-pineapple core crude extract-derived bromelain (PCB) was separated by Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) followed by Coomassie Brilliant Blue (CBB) staining to ensure the presence of bromelain. In cytotoxic test, NIH-3T3 fibroblast cultures were treated with extracts in various concentrations to for 24 or 48 hours. Number of fibroblasts was calculated using 3-(4,5-dimethylthiazol-2- yl)-2,5-Diphenyltetrazolium bromide (MTT) assay. RESULTS: Pineapple core extraction using maceration method produced relative high yield (concentration: 1.5424 g/mL) of bromelain, which was confirmed by CBB staining results with the molecular weight of 33 kDa. Based on cytotoxic test results of PCB on NIH-3T3 fibroblasts, 24-hours-incubation LD50 was 95.7 g/L, while 48-hoursincubation LD50 was 51.1 g/L. CONCLUSION: PCB has low cytotoxic effect in NIH-3T3 fibroblasts.
... The plant extracts are collectively known as bromelain. Medicinal properties of bromelain are brought about synergistically by an array of enzymes present in it 4 . Stem bromelain, the major cysteine protease of the extract from pineapple stem, is commercially available 5 . ...
Article
Deposition of fibrils originating from monomeric β- amyloid (Aβ) peptide in brain cells is responsible for progressive neuronal damages in Alzheimer's disease. Peptides from bromelain, a cysteine protease from Ananas comosus (pineapple), were generated after digestion with proteases under conditions similar to human gastrointestinal tract. These peptides not only inhibit the growth of Aβ-amyloid aggregates, but also irreversibly destabilize the preformed aggregates. Gel filtration followed by mass spectrometric analysis identified a pool of peptides of < 700 Da in the digest. Probable composition of the peptides interacting with Aβ-peptide was predicted from homology alignment between Aβ-peptide and bromelain using bioinformatics tools. Corresponding synthetic peptides can also destabilize the preformed aggregates as observed from thioflavin T assay, transmission electron microscopy and atomic force microscopy. Aβ aggregates that were preincubated with the bromelain-derived peptides did not exert appreciable toxicity on human neuroblastoma cells (SH-SY5Y) cultured in vitro.
... A combined effect of quercetin and bromelain effectively suppresses the allergic reactions and the excessive inflammation resulting from bruising and tissue damage. This attribute of quercetin has emphasised the researchers to focus in the intervention of allergic reactions (29). ...
Article
Quercetin, the most active bioflavonoid which is produced as a secondary metabolite by plants, is a polyphenol with a wide spectrum of bioactivities. This bioflavonoid is the ―nature‘s biological response modifier‖ as it interferes with the various allergens and other reactive compounds. Apple, oranges, tomatoes, onions, black tea and green tea are good sources of quercetin and it is also available commercially. After absorption in the small intestine and colon, quercetin conjugates with glucuronic acid and binds to albumin and passes to liver and benefits the body by its various bioactivities. Quercetin‘s antioxidant activity enhances the radical scavenging activity and metal chelation of the ions but the prooxidant activity depends on its high concentration. Further, quercetin interferes with the formation of leukotrienes from arachidonic acid showing its anti-inflammatory effect. A combined effect of quercetin and bromelain effectively suppresses the allergic reactions and the excessive inflammation resulting from bruising and tissue damage. The mutualistic effect of vitamin C and quercetin protects each other from getting oxidized. A direct relationship was also found to exist between quercetin's antiviral activity and enhancement of cyclic adenosine monophosphate (cAMP), which is a second messenger involved in many biological processes. Quercetin helps in down regulation of mutant gene p53 and inhibits the growth of cancerous cells by putting a check at G1 phase. This also controls the surpassing of the normal regulatory growth by the tumor cells and inhibits the production of heat shock proteins and thus showing its anticancer properties. Owing to the potential pharmaceutical properties of quercetin, the bioactivities, principle uses and mechanisms involved in the treatment of various diseases were reviewed in this paper. In addition, safety issues involved in the partake of quercetin by humans have also been discussed.
... 4 The other substances typically include peroxidase, acid phosphatase, protease inhibitors and calcium. 5,6 Absorption and Bioavailability ...
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A substance called bromelain found in Pineapple juice and stem has become a popular nutritional supplement. Bromelain contains enzymes with a range of potent effects. Bromelain has also been reported to have beneficial effects on the digestive, respiratory and circulatory systems and possibly on the immune system. Bromelain is also used to treat swelling and inflammation following surgery, especially sinus surgery it use as a natural remedy for easing the symptoms of arthritis, including pain and joint stiffness. The present review states the uses of Bromelain in various diseases such as Cancer, Respiratory Conditions, Ulcers etc. and also states the biosynthesis and its mode of action with various Drug interactions.
... Irreversible conformational changes occur at pH values higher than 10.3 [22]. Some other minor cysteine endopeptidases (ananain, comosain) are also present in the pineapple stem bromelain among a complex mixture of different thiol-endopeptidases and other partially characterized components such as phosphates, glucosidases, peroxidases, cellulases, glycoproteins and carbohydrates, among others [26,34]. ...
... Bromelain is well tolerated in high doses (CHOBOTOVA et al., 2010). The LD 50 for bromelain is greater than 10 g/kg and dosages up to 1.5 g/kg/day in rats exert no side effects (KELLY, 1996). ...
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This experiment was conducted to evaluate the effects of dietary bromelain supplementation on laying performance, egg nutrient profile, serum traits and antioxidant status. A total of 96 Lohmann White laying hens (28-weeks-old) were fed diets containing different concentrations of bromelain (0, 0.15, 0.30 and 0.45 g/kg) during an 8-weeks experimental period. Each treatment was replicated in six cages. Data were analysed using the GLM Procedure, including orthogonal (control vs. bromelain) and polynomial (dose-response) contrasts statements. Bromelain supplementation did not affect the laying performance and egg quality parameters. Bromelain supplementation increased egg yolk (P < 0.0001) serum protein (P < 0.04) concentrations, decreased egg yolk triacylglycerol fraction (P < 0.0001) and serum cholesterol concentration (P < 0.0003), but did not affect egg yolk cholesterol fraction. Hens fed diets supplemented with the bromelain had higher concentrations of antioxidant enzymes (265 vs. 210 U/g protein for superoxide dismutase; 16.31 vs. 7.95 U/g Hb for glutathione peroxidase and 4.70 vs. 2.33 U/g Hb for glutathione-S-transferase; P < 0.0001) and lower malondialdehyde (114 vs. 86 nmol/ml, P < 0.05) in serum than hens fed the control diet. In conclusion, bromelain could be supplemented up to 0.45 g/kg in the laying hen diet to enhance antioxidant capacity.
... Bromelain can be extracted from the waste peel, core, and stem fruit of the Bromeliaceae or pineapple family, mostly from Ananascomosus Merr., sp. (Kelly, 1996;Chaurasiya and Hebbar, 2013). Bromelain has a proteolytic enzyme of papain can breakdown myofibrillar proteins and collagen and causes tenderness in meat Different studies reported that bromelain and papain were found useful on duck (Buyukyavuz, 2014), beef (Chaurasiya et al., 2015;Ionescu et al., 2008;Istrati et al., 2012), fish (Feng et al., 2017), pork and chicken (Ketnawa et al, 2012). ...
Article
Meat tenderness is one of the quality parameters that affect the tough muscle and changes into soft meat, which is characterized by, increased the palatability, juiciness, and flavor of the meat, the process is known as meat tenderization. According to literature reports, meat can be tenderized by using different methods. The tenderize meat gives rise to customer satisfaction and repeated buyers that improve the value of the meat industry as well as the restaurants. The most widely used methods for tenderization of meat are mechanical, electrical stimulation, application of exogenous proteolytic enzyme, and thermal treatment methods. All these methods result in tenderization of meat that reduces the cooking times, hardness of meat and chewiness of meat products, that can increase meatiness, flavor, and overall palatability. Therefore, an attempt has been made to review the different meat tenderization methods concerning their effectiveness, economic value, and mode of action. The toughness of the meat is reduced during mechanical method by disrupting the structure of the meat and weakening the protein network in muscles. Whereas, in case of enzymatic treatment tenderization is achieved by hydrolyzing the meat protein, which reduces the bonding between muscles and results in softening of the meat.
... This produces a demarcation between living and dead tissue. 16 Bromelain has been broadly used in food industry; for meat tenderization, protein hydrolysate production and as active element to provide gentle peeling effects in cosmetic industries. 17 In textile industries, bromelain is used for decomposing or partially solubilizing protein fiber from silk and wool. ...
Article
Aim: The aim of the study was to evaluate and compare bromelain with papain as the chemomechanical caries removal agent in relation to their efficacy. Materials and methods: Thirty extracted primary molars with active carious lesion extending into dentin were selected. The samples were randomly divided into groups by sectioning the samples into two halves. Group I-cavity prepared using papain gel; group II-cavity prepared using bromelain gel. Time taken for caries removal in both the groups (I and II) was recorded with the help of a stopwatch. Following caries removal, the amount of remaining demineralized dentin was measured with the help of stereomicroscope and weld check (biological image analysis) software. Results: t test is used to evaluate the significance of study parameters on continuous scale between two groups on metric parameters. The mean of residual carious dentin thickness obtained from the group II (bromelain) was 36.74 μm, which was much lower than that obtained from group I (papain) with a mean of 73.84 μm. The mean time taken in the group II (bromelain) was 335.30 seconds which was nearly equal to the mean time of group I (papain) of 352.33 seconds. Conclusion: The amount of remaining demineralized dentin was found to be lower in bromelain group than the papain group and time taken for the carious dentin removal was almost found similar in both bromelain and papain groups. It may be concluded that bromelain was more effective in amount of caries removal than papain. Clinical significance: Chemomechanical caries removal with the organic gels pose a great benefit as they are less invasive and has low side effects and cost-effective. How to cite this article: Reddy VK, Nagar P, Reddy S, et al. Bromelain vs Papain Gel for Caries Removal in Primary Teeth. J Contemp Dent Pract 2019;20(11):1345-1349.
... Hu et al. (2020) reported that bromelain could inhibit the absorption of fatty acids and the secretion of Very Low-Density Lipoprotein (VLDL), further reported that giving bromelain as much as 20 mg/kg in rats fed a high-fat diet for 12 weeks can reduce glycerol levels and fat accumulation in the liver. Bromelain breaks down the plaque on the walls of blood vessels improving blood circulation (Kelly, 1996). Previous researchers reported that bromelain enzyme in laying hen ration can reduce both blood serum and liver cholesterol (Lien et al., 2012;Yenice et al., 2019). ...
... Bromelain is a general name for a family of sulfhydryl proteolytic enzymes obtained from Ananas comosus, the pineapple plant. 1 It is typically distinguished as either fruit bromelain or stem bromelain, with the majority of commercially available bromelain derived from the stem. 2 First identified in pineapple juice in 1891, it has been manufactured on a large scale as nutritional dietary supplement since 1957. To date, eight proteolytically active constituents have been isolated from bromelain. ...
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Introduction Bromelain is a complex mixture of thiol proteases and other non-proteolytic constituents, commercially extracted primarily from the pineapple stem. Evidence from several in vitro and in vivo studies highlights its excellent bioavailability, lack of side effects, and broad spectrum of medical efficacies, of which the antiphlogistic properties are among the most valuable ones. Bromelain has indeed been employed for the efficient treatment of many inflammatory disorders, ranging from osteoarthritis and inflammatory bowel diseases to cancer-related inflammation. Methods The aim of the current study was to assess the anti-inflammatory effects of bromelain after gastrointestinal digestion simulated in vitro using stomach, intestinal, and chondrocyte human cellular models (AGS, Caco-2, and SW1353, respectively). Results We successfully demonstrated the capability of bromelain to reduce an inflammatory stimulus by reproducing its exposure to the gastro-enteric environment in vitro and assaying its effect in human cell lines derived from stomach, intestinal, and chondrocytes. Conclusion Consistently with the previously published data, our work underpins the relevance of bromelain in the development of safer and more effective anti-inflammatory therapies.
... 21 Bromelain is extracted from the stem and fruit of Pineapple (Ananascomosus) plant. 22 In the current study a significant difference was observed in the L* and b*parameters for Biomed ® Superwhite toothpaste whereas no significant difference was observed in the pre and post brushing values in any parameters for Himalaya ® Sparkling white toothpaste. In studies reported by Kalyana et al. 10 , and Patil et al. 23 , the ability of these proteolytic enzymes was demonstrated. ...
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Aim: To compare and assess the efficacy of three toothpastes compared to prophylactic polishing paste as iron stain removal method in extracted primary teeth. Sixty extracted primary anterior teeth were decoronated at cementoenamel junction, followed by filling the pulp chamber with flowable composite. The teeth were then immersed in ferrous sulphate solution and digital images were obtained. The teeth were subjected to electric tooth brushing using Colgate ® ABSTRACT Aim: To compare and assess the efficacy of three toothpastes compared to prophylactic polishing paste as iron stain removal method in extracted primary teeth. Method: Sixty extracted primary anterior teeth were decoronated at cementoenamel junction, followed by filling the pulp chamber with flowable composite. The teeth were then immersed in ferrous sulphate solution and digital images were obtained. The teeth were subjected to electric tooth brushing using Colgate ®
... Bromelain's LD50 is >10 g/ kg in rodents, 12 g/day orally is a safe dose for humans, without signifi cant side effects [6,7]. proteinases contribute to anti-infl ammatory activity in vivo andit is poorly absorbed when given orally, with resulting plasma levels less than 10 ng/ml in humans given 4 g/day [8,9]. ...
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The SARS-CoV-2 infection has led to a global pandemic which has led to almost 4 million deaths worldwide. However, to date, a specifi c antiviral drug does not exist to treat the disease and control the virus. Here, we focus on the potential use of bromelain in line with its anti-oxidant, anti-infl ammatory, and immunomodulatory effects. Additionally, bromelain exerts fi brinolytic, anti-invasive and antithrombotic activities that may become a therapeutic candidate against SARS-CoV-2 infection. In this paper, we focused on bromelain's therapeutic potential concerning its potential role in reducing the severity of symptoms and the adverse effects of other antiviral drugs currently being used. The therapeutic effects of bromelain suggests that it may reduce mortality and morbidity rates in patients with CoVID-19 infections, through its anti-oxidant, anti-infl ammatory, immunomodulator and anticoagulant effects. These positive effects leads us to propose that bromelain may be clinically valuable in the treatment of COVID-19 and that it therapeutic attributes should be fully investigated.
... Bromelain obtained from the fruit or the stem of pineapple (Ananas comosus) by simple processes is mostly made up of a mixture of thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, esterase and several protease inhibitors [1]. Clinically, bromelain is used to treat inflammation in cases such as rheumatoid arthritis, soft tissue injuries, inflammation of the colon, chronic pain and asthma [2][3][4]. The sensitivity of the enzyme to conditions such as high acidity, gastric proteases in the stomach juice, chemicals, organic solvents and elevated temperature limits its therapeutic application [5,6], hence the need for its stabilization. ...
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The therapeutic application of bromelain is limited due to its sensitivity to operating conditions such as high acidity, gastric proteases in the stomach juice, chemicals, organic solvents and elevated temperature. We hypothesized that bromelain immobilized on probiotic bacterial spores would show enhanced therapeutic activity through possible synergistic or additive effects. In this study, the oedema inhibition potential of bromelain immobilized on probiotic Bacillus spores was compared to the free enzyme using the carrageenan paw oedema model with Wistar rats. In batch A rats (carrageenan-induced inflammation 30 min after receiving oral treatments), group 7 rats treated with a lower dose of spore-immobilized bromelain suspension showed the highest oedema inhibition, 89.20 ± 15.30%, while group 4 treated with a lower dose of free bromelain had oedema inhibition of 60.25 ± 13.00%. For batch B rats (carrageenan-induced inflammation after receiving oral treatment for three days), group 7 rats treated with a lower dose of spore-immobilized bromelain suspension showed higher inhibition percentage (81.94 ± 8.86) than group 4 treated with a lower dose of free bromelain (78.45 ± 4.46) after 24 h. Our results showed that used alone, the enzyme and the spores produced oedema inhibition and improved the motility of the rats. The spore-immobilized bromelain formulation performed approximately 0.9-fold better than the free bromelain and the free spores at the lower evaluated dose.
Article
Aims Diabetes, a serious worldwide problem, is modulated via inflammation and oxidative stress. Bromelain, a natural compound, recently attracts interest due to its anti-inflammatory effects, while its mode of action remains not properly understood. Thus, investigating the antidiabetic effect of bromelain is promising. Materials and methods Rats were randomized into normal group, STZ group (administrated single intraperitoneal (i.p) injection of 55 mg/kg streptozotocin (STZ)) and STZ + Bro group (administrated single i.p injection of STZ, 72 h later were i.p administrated 10 mg/kg/day bromelain for 15 days). Wound healing ability was investigated for different groups. Spectrophotometry, ELISA, histopathological and immunohistochemical techniques were applied. Key findings Bromelain significantly decreased fasting blood glucose, serum triglycerides and cholesterol and hepatic malondialdehyde levels compared with STZ group. Moreover, Bromelain significantly increased serum albumin and total protein levels and percentage of wound healing compared with STZ group. These results were confirmed through the histopathological examination of liver, pancreas, and skin tissues. Investigating the molecular mechanism underlying these effects, STZ injection caused significant increase in hepatic oxidized-LDL (Oxi-LDL) and lysophosphatidic acid (LPA) levels and hepatic lysophosphatidic acid receptor 1 (LPAR1), and beta secretase (BACE1) protein tissue expressions, while bromelain significantly aborted these effects. Thus, STZ caused upregulation of Oxi-LDL/LPA/LPAR1/BACE1 pathway, while bromelain significantly ameliorated these effects. Significance To our best knowledge, this study represents the 1st study investigating Oxi-LDL/LPA/LPAR1/BACE1 pathway in STZ-induced diabetes in rats, in addition to the promising ameliorative effect of bromelain in STZ-induced diabetes in rats.
Article
Bromelain is a crude protein extract obtained from pineapple fruit and stem, which comprises a variety of proteolytic enzymes. It applied for reduction of muscle and tissue inflammation, alleviation of bronchitis and sinusitis, as an aid in digestion and for relieving symptoms of gout. The most important application of bromelain includes meat tenderization. Pineapple was peeled and crushed to extract the juice containing soluble bromelain enzyme. Further processing includes precipitation, dialysis and ion exchange chromatography of enzyme. Ion exchange elutes (pure enzyme) reveal the activity of bromelain by titrimetric enzyme assay method. Further, the enzyme was immobilized for commercial uses. Finally, the enzyme was applied for meat tenderization to check the effectiveness of extracted bromelain. It exhibits potential therapeutic activities and other industrial uses.
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The aim of this study was to investigate the effects of bromelain and papain enzymes for tenderizing of squid (Loligo vulgaris) muscle. Squid samples were immersed into the enzyme solutions and then they were kept in a water bath at 60 °C for 20 min to activate enzymes. After enzyme treatment, pH values, hardness and shear force values of squid muscle decreased. Total protein, free amino acid contents and sensory scores increased. Use of bromelain and papain enzymes was found as effective method to tenderize of squid muscle. Better results were obtained with papain compared to bromelain.
Chapter
The pineapple, botanically named Ananas comosus, has been used for centuries as a folk medicine by the indigenous inhabitants of Central and South America. The medicinal qualities of the plant are attributed to bromelain, the aqueous extract of the pineapple, which has been available as a pharmaceutical product since 1957. The beneficial effects of bromelain are attributable to its multiple constituents. Bromelain is primarily comprised of sulfhydryl-containing proteolytic enzymes. It also contains escharase (a nonproteolytic component with debriding effects), peroxidases, phosphatases, glucosidases, cellulases, several protease inhibitors, glycoproteins, carbohydrates, and organically bound calcium. Bromelain has been shown to interact with a variety of effectors and pathways involved in physiological processes such as inflammation, immune response, and coagulation. Bromelain has been used as a supplement with health benefits, and also tested, alone or in combination with other agents, in preclinical and clinical settings for the management of a number of clinical conditions, including infections, inflammatory diseases, musculoskeletal injuries, and thrombotic and ischemic disorders. As an anticancer agent, however, bromelain has been the subject of limited preclinical and clinical observations. In this chapter, history, pharmacological features, potential and actual applications, and safety profile of bromelain are reviewed.
Chapter
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Article
Bromelain is a mixture of proteolytic enzymes found in pineapple (Ananas comosus) plants. Bromelain can be found in several parts of the pineapple plant, including the stem, fruit, leaves and peels. High demand from bromelain has resulted in gradual increases in bromelain production. Such increases in production have led to the need for a bromelain production strategy that yields more purified bromelain at a lower cost and with fewer productions steps. Previously, bromelain was purified using conventional centrifugation, ultrafiltration and lyophilisation. Recently, the developments of more modern purification techniques such as gel filtration, ion exchange chromatography, affinity chromatography, aqueous two phase extraction and reversed micelle chromatography have resulted in increased industrial bromelain production worldwide. In addition, recombinant DNA technology has emerged as an alternative strategy for producing large amounts of ultrapure bromelain. An up-to-date compilation of data regarding the commercialisation of bromelain in the clinical, pharmaceutical and industrial fields is provided in this review.
Chapter
Enzymes are proteins that act as highly efficient catalysts in biochemical reactions. This catalytic capability is what makes enzymes unique and they work efficiently, rapidly, and are biodegradable. The use of enzymes frequently results in many benefits that cannot be obtained with traditional chemical treatments. These often include higher product quality and lower manufacturing cost, less waste, and reduced energy consumption. Industrial enzymes represent the heart of biotechnology processes and biotechnology (Whitehurst and van Oort 2009; Sabalza et al. 2014)
Conference Paper
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Introduction: Bengkuang (Pachyrizus erosus (L.) Urb) contains 86-90% water, phenol, and saponins. In substance fenolida Bengkuang effective in inhibiting the formation of melanin so pigmentation, due to sun can be reduced making it suitable for skin in the tropics such as Indonesia, including Bengkulu Province. Objective: In this study the gel was formulated and evaluate starch bengkuang formulation with varying HPMC is gelling agent. Method: This research is an experimental study. Gel made in 3 formulas at concentration of starch bengkuang every formula 5 gr with different HPMC F1,F2,F3 with a concentration of 3%,5%,7%. Results: Gel from starch bengkuang was evaluated for 3 weeks, from the research starch bengkuang with gelling agent HPMC can be formulated into gel preparations, Gel with a concentration of HPMC 3% in F1 is the best preparation. The form of moderately viscous, rose fragrant, homogeneous with a pH of 6 and the spread of 5-7 cm, not irritate the skin and From the results of visual observation there is no the growth of bacterial and fungi in the gel. Conclusion: Starch bengkuang with gelling agent HPMC preparation gel can be made in various concentrations. The physical properties gel a variation of the starch bengkuang does not affect the stability physical gel and has not change for storage. Keywords: starch bengkuang_Pachyrizus erosus_preparation gel_HPMC
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Proteinases have the potential to effect partial solubilization of the proteinaceous gum sericin involved in binding the silk strands together in cocoon, an essential step in the silk cocoon cooking and reeling. Therefore, pineapple extract rich in cysteine proteinases was enzymologically characterized for its potential application in oak tasar (Antheraea proylei J.) silk cocoon cooking and reeling. Optimum sodium carbonate concentration (9.8 mM) and optimum temperature (60ºC) for the proteinase activity were determined. Though relatively thermostable, an enhanced activity loss was observed when the extract was incubated in the temperature range 70-90ºC with sodium carbonate. Bulk of the activity (80-83%) remained after 1 hr of time-dependent inactivation at 60ºC. The tasar cocoon extract neither caused inhibition of the activity nor enhanced its time-dependent loss by incubation at 60ºC. However, it caused an enhanced time-dependent loss of the activity by incubation at 60ºC with sodium carbonate. Considering these enzymological characteristics, experimental cocoon-cooking media were constituted by taking the pineapple extract with or without sodium carbonate at room temperature or 60ºC. The results of the cocoon cooking and subsequent single silk filament reeling indicated for an applicability of pineapple extract as an effective agent for the oak tasar cocoon cooking and reeling.
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Bromelain is a cysteine protease which is found in the tissues of Bromeliacea plant family of which pineapple Ananas cosmossus is best known. The investigated parameters for optimal Brome-lain extraction are optimum buffers, pH, Molarity, time, and amounts of husk free pineapple fruit to volume (ml) of buffer ratio. Sodium phosphate was best buffer for bromelain extraction from pineapple fruit because its showed high activity, with casein as a substrate. Subsequent experiments, using sodium phosphate as an optimal buffer for extraction and casein as a substrate, reviled that the optimal bromelain extraction conditions were achieved at pH 7.0, 0.1 M of sodium phosphate, 2.5 min of extraction time, 1:0.5 (gm of pineapple fruit/ v of sodium phosphate buffer) extraction percentage , and 30 min of incubation time. Additionally, Bromelain extracted from pineapple fruit showed a maximum enzyme activity at pH 7and at 30 min of incubation with casein as substrate.
Article
Fruit bromelain is a cysteine protease accumulated in pineapple fruits. This proteolytic enzyme has received high demand for industrial and therapeutic applications. In this study, fruit bromelain sequences QIM61759, QIM61760 and QIM61761 were retrieved from the National Center for Biotechnology Information (NCBI) Genbank Database. The tertiary structure of fruit bromelain QIM61759, QIM61760 and QIM61761 was generated by using MODELLER. The result revealed that the local stereochemical quality of the generated models was improved by using multiple templates during modelling process. Moreover, by comparing with the available papain model, structural analysis provides an insight on how pro-peptide functions as a scaffold in fruit bromelain folding and contributing to inactivation of mature protein. The structural analysis also disclosed the similarities and differences between these models. Lastly, thermal stability of fruit bromelain was studied. Molecular dynamics simulation of fruit bromelain structures at several selected temperatures demonstrated how fruit bromelain responds to elevation of temperature.
Article
BACKGROUND: Chronic venous disease (CVD) is major health concern; however, there remains a need to improve treatment approaches. Nédemax® Mese, a nutritional supplementation consisting of Leucoselect® 300 mg, Lymphaselect® 100 mg and Bromelain 100 mg, is a patented formulation that may have a role in the treatment of CVD. In this prospective, multicenter study conducted at 54 Italian centers, we investigated the effectiveness of Nédemax® Mese in a large sample of CVD patients. METHODS: Patients with CVD received Nédemax® Mese (1 tablet/day) and/or standard compression stockings for a period of 90 days. RESULT S: In total, 648 patients were enrolled: 165 (25%) received standard compression stockings, 252 (39%) compression stockings + Nédemax® Mese and 231 (36%) Nédemax® Mese only. Overall, patients receiving standard compression stockings + Nédemax® Mese showed a more severe status at baseline. A significant reduction in the malleolus circumference, both at the right and the left limb, was reported in all groups. This reduction was more evident with compression stocking + Nédemax® Mese (-7.5% vs. -4.5% with Nédemax® Mese only and -3.3% with standard compression stocking). A similar pattern was reported for symptom severity and severity of disease. Circumference of calf, knee and metatarsal decreased significantly, in a more evident fashion with Nédemax® Mese, either in combination or as a monotherapy. © 2019 EDIZIONI MINERVA MEDICA. CONCLUSIONS: Nédemax ® Mese, either as monotherapy or in association with standard compression stockings, can provide a marked and sustained benefit in patients with CVD.
Article
Several in vitro studies along with some in vivo studies have shown the anti-cancer activity of bromelain against several types of cancer except cervical cancer. This study is focused to address the therapeutic effect of bromelain on a human cervical cancer cell line in vitro using HeLa cells. Here, the IC50 dose of bromelain enhanced Hela cell apoptosis at a concentration of 100 μg/ml after 48 h treatment, which is statistically significant compared to the dose of 50 μg/ml (p < 0.01). The percentage of live cells was reduced to about 48% and the percentage of apoptotic cells has increased to about 47% at the IC50 dose of bromelain with a 48 h exposure. Significant proportions of HeLa cells were observed to undergo apoptosis via the p53-dependent pathway in a ROS-independent manner at 100 μg/ml after 48 h treatment. In addition to that, bromelain also inhibited the formation of colonies and the migratory ability of HeLa cells. The present study reports that bromelain can act in an apoptotic pathway on human cervical cancer cell line HeLa.
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The pineapple plant (Ananas comosus) was shown to contain at least four distinct cysteine proteinases, which were purified by a procedure involving active-site-directed affinity chromatography. The major proteinase present in extracts of plant stem was stem bromelain, whilst fruit bromelain was the major proteinase in the fruit. Two additional cysteine proteinases were detected only in the stem: these were ananain and a previously undescribed enzyme that we have called comosain. Stem bromelain, fruit bromelain and ananain were shown to be immunologically distinct. Enzymic characterization revealed differences in both substrate-specificities and inhibition profiles. A study of the cysteine proteinase derived from the related bromeliad Bromelia pinguin (pinguinain) indicated that in many respects it was similar to fruit bromelain, although it was found to be immunologically distinct.
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The reactivity of sera from honeybee venom allergic patients with the N-glycan of phospholipase A2 was investigated using neoglycoproteins with an enzyme-linked immunosorbent assay. Of 122 sera with appreciable levels of IgE antibodies directed against bee venom as measured by radioallergosorbent test, 34 sera exhibited significant amounts of glycan-reactive IgE. These sera cross-reacted with the N-glycan from the plant glycoprotein bromelain. The interaction of IgE with the N-glycan from phospholipase could be inhibited with glycopeptides from bromelain which shares the alpha 1,3-fucosylation of the asparagine-bound N-acetylglucosamine with bee venom phospholipase. Since defucosylated bromelain glycopeptides or glycopeptides containing a Man3GlcNAc2 oligosaccharide were not recognized by most of these sera, we conclude that alpha 1,3-fucosylation of the innermost N-acetylglucosamine residue of N-glycoproteins forms an IgE-reactive determinant. This structural element is frequent in glycoproteins from plants, and it occurs also in insects. It is suspected to be one of the major causes of the broad allergenic cross-reactivity among various allergens from insects and plants.
Article
Bromelains consist of a group of proteolytic enzymes of Bromeliaceae. They are commonly used in pharmaceutical industries, food production and in diagnostic laboratories. Bromelains are known to cause IgE-mediated reactions of both the immediate type and the‘late phase reaction of immediate type reaction’ with predominantly respiratory symptoms. We report four cases of occupational allergy to bromelain in workers of a blood grouping laboratory. These observations prompted us to investigate the sensitization rate to bromelain in all workers of the particular diagnostic laboratory who had contact with bromelain. These results were compared with those obtained from healthy, randomly selected individuals without evident bromelain exposure. Our findings indicate that (i) bromelain is a strong sensitizer, (ii) sensitization usually occurs due to inhalation and not to ingestion, (iii) bromelain allergy is occupationally acquired, and adequate precautions are necessary. We can further state that (iv) skin testing with relatively pure allergens such as isolated proteases like bromelain may induce systemic reactions, even at very high dilutions.
Article
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.
Article
The effect of oral bromelain upon blood pressure and heart rate of 19 patients has been studied. Dosage of bromelain up to twice the maximum recommended had no effect upon blood pressure or heart rate. When the dosage was increased up to 8 times the maximum recommended, the heart rate increased proportionately with the amount administered. Blood pressure however, remained unchanged. These findings suggest that oral bromelain is safe and add further evidence to the hypothesis that the effect of bromelain is related to its action on endogenous prostaglandins.
Article
To investigate a physiological function of substance P (SP) present in the peripheral ending of sensory neurons, we determined immunoreactive SP (iSP) levels in the s.c. perfusate and the amount of edema evoked in rat paw by noxious heat stimulation. We found that immersion of rat paw into hot water (47 degrees C) for 30 min led to a significant increase of iSP in the perfusate and about 50% increase in paw volume. Neonatal pretreatment with capsaicin inhibited significantly the increase in both iSP and paw volume evoked by noxious heat stimulation. Acute and chronic denervation of the sciatic and saphenous nerves also inhibited the heat-evoked iSP release and edema remarkably. Intraplantar injection of SP evoked an increase in paw volume in dose-dependent manner. This increasing effect of SP on paw volume was more substantial than that produced by histamine. Simultaneous treatment with stem bromelain and emorfazone decreased significantly the heat-evoked iSP release and edema. These results suggest that 1) SP produced by noxious heat stimulation in the periphery may be released from the afferent fibers with small-diameter, 2) bradykinin may intervene in this SP release and 3) SP released in the periphery may be closely related to the edema formation of the thermal injury reaction.
Article
Bromelain, a proteolytic enzyme extracted from pineapple plants, was investigated for its capacity to interfere with arachidonic acid metabolism, since prostaglandins and other eicosanoids are well-known to be involved in the pathogenesis of inflammatory diseases. Bromelain was tested for its ability to interfere with eicosanoids generation in vivo in two experimentally-induced inflammatory reactions in the rat. Also antiplatelet aggregation activity of bromelain was studied in ex vivo rat platelets. The results seem to indicate an interference of bromelain with arachidonic acid cascade, which, however, deserves further investigation to be better assessed.
Article
The effects of stem bromelain on the plasma kallikrein system, bradykinin levels and plasma exudation at the inflammatory site were examined in rats with a kaolin-induced inflammation of an air pouch. Bromelain (5, 7.5 mg/kg) caused a dose-dependent decrease of bradykinin levels at the inflammatory site and a parallel decrease of the prekallikrein levels in sera. Plasma exudation was also reduced dose dependently. Bradykinin-degrading activity in sera was elevated after treatment with bromelain, although it was unchanged in the pouch fluid. These data indicate that bromelain inhibits plasma exudation through inhibiting the generation of bradykinin at the inflammatory site via depletion of the plasma kallikrein system.
Article
Bromelain, a pineapple-derived plant product, added to C57Bl/6 mice laboratory chow decreased lung metastasis of Lewis lung cancer cells implanted s.c. This antimetastatic potential was demonstrated by both the active and inactive bromelain with or without proteolytic, anticoagulant properties.
Article
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 26-32,000 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.
Article
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.
Article
The dose-response relationship between the frequencies or concentration of exposure to powdered drug allergens and drug induced allergic onsets was studied in a pharmaceutical plant for 15 years from 1974 to 1984. The subjects were 41 male workers and the target allergens were two kinds of anti-inflammatory enzymes (Bromelain and Trypsin) and three kinds of antibiotics (Ampicillin, Amoxycillin and Cephalexin). The allergic onsets were confirmed by periodic allergological examinations and occasional clinical findings. Statistical analysis was made by the person-year method. The results showed that in workers who had any allergic history, the incidence rates of allergic onsets increased with elevation in the frequencies or concentration of exposure to these allergens, while in the cases without such history, the incidence rates increased only in those with high frequencies of exposure to the allergens. The findings suggest that the incidence rates of occupational drug allergy were dependent on the frequencies and concentration of exposure to allergens.
Article
The levels of high molecular weight (HMW) kininogen and pre-kallikrein in rat plasma were markedly reduced after single injection of bromelian (10 mg/kg, i. v.) and gradually recovered over a 72 hour period. The level of low molecular weight (LMW) kininogen, however, was not changed during this period. Rat pleurisy was induced by intrapleural injection of λ-carrageenin. The levels of HMW kininogen and prekallikrein, but not of LMW kininogen, in the exudate were markedly decreased, when compared with those in plasma of the same animals. After pretreatment with disulfiram, oral administration of ethanol (2 g/kg) or intravenous injection of acetaldehyde (10 mg/kg) to rats caused significant effect on the plasma HMW kininogen and prekallikrein levels. These results suggest that HMW and LMW kininogens may be consumed separately in vivo and play different roles.
Article
Proteolytic enzymes of animal, bacterial, mould or plant origin are used in many industrial processes, e.g. in the detergent, food and pharmaceutical industries as well as in medicine. The allergenic potency of these enzymes should not be underestimated, for they cause, in particular, IgE-mediated respiratory allergies. The risk of sensitization to enzymes due to inhalation as a result of occupational exposure is very high (up to 50%), and therapeutic applications are also not without risk. Therefore, the utmost care should be taken in the production and handling of pulverized enzymes and their inhalation should be avoided. Papain and Bromelain are used as tenderizers of meat and to clarify beer. Therefore, these enzymes are also potential ingestive allergens and may represent an unrecognized cause of an allergic reaction following a meal. As contact allergens the enzymes play a minor role; biodetergents in particular present no increased risk of skin damage for the user.
Article
Zusammenfassung Die orale Verabreichung von Bromelain in Form von 2 Ananase®-100-Tabletten an freiwillige Versuchspersonen verminderte bei diesen die Empfänglichkeit für die durch ADP induzierte Aggregation der Blutplättchen.
Article
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.
Article
The stem of the pineapple plant contains, in addition to a number of proteases, particularly bromelain, a non-proteolytic component which is responsible for the complete bridement of experimental burns by an "enzymatic dissection" between the viable native and the non-viable denatured burn tissue. With very little scraping, using a tongue depressor, all of the eschar can be removed and a bed suitable for grafting results. This "Escharase" has a molecular weight of 45,000 daltons and is a trimer made up of three identical subunits weighing 15,000 daltons each; it has an isoelectric point of pH 6.04 and has no hydrolytic enzyme activity against normal protein substrates or various glycosaminoglycan substrates. It can be concentrated by membrane ultrafiltration in a molecular weight range between 30,000 and 50,000 daltons and be purified by isoelectric focusing. The biological activity of the Escharase is not dependent on sulfhydryl groups nor upon the contaminating bromelain activity. The Escharase activity varies enormously from preparation to preparation, but the ultrafiltration procedure tends to concentrate Escharase activity to a fairly constant amount.
Article
The edema producing property of a proteolytic enzyme (bromelain), which was parenterally or intraduodenally applied, was investigated in a traumatically induced hindleg edema in rats. Under standardized conditions the hindlegs were squeezed by a wringer and swelling was volumetrically measured. Whereas after enteral application of bromelain a significant reduction of the edema could be observed, the parenteral application only resulted in a minimal therapeutic effect. Although enterally applied enzymes are thought to be degraded in the gut, the better results were obtained after enteral administration of bromelain. This supports the observation that also enzymes can be absorbed by the gut without loosing their biological properties.
Article
The thiol protease bromelain has been shown to remove T-cell CD44 molecules from lymphocytes and to affect T-cell activation. We investigated the effect of a highly purified bromelain protease F9 (F9) on the adhesion of peripheral blood lymphocytes (PBL) to human umbilical vein endothelial cells (HUVEC). Preincubation of the lymphocytes with F9 reduced the adherence to about 20% of unstimulated and to about 30% of phorbol-dibutyrate (P(Bu)2) stimulated lymphocytes. Using flow cytometry, both crude bromelain and protease F9 reduced the expression of CD44, but not of LFA-1, on PBL. F9 was about 10 times more active than crude bromelain; at 2.5 micrograms/ml of F9 about 97% inhibition of CD44 expression was found. A mAb against CD44 was tested and found to block the F9-induced decrease in PBL-binding to HUVEC. The results indicate that F9 selectively decreases the CD44 mediated binding of PBL to HUVEC.
Article
In vitro treatment of human peripheral blood mononuclear cells (PBMNC) with proteolytic enzymes (bromelain, papain) and amylase leads to the production of large amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) in a time and dose dependent manner. Increased TNF-alpha and IL-6 production was already found after 4-6 hours of incubation, and plateau levels were reached after 12-16 hours. Plateau levels up to 1500 pg TNF-alpha/ml/10(6) PBMNC, 13000 pg IL-1 beta/ml/10(6) PBMNC, and 23000 pg IL-6/ml/10(6) PBMNC were observed. Control cultures contained below 35 pg/ml/10(6) PBMNC of TNF-alpha, IL-1 beta or IL-6. In contrast to TNF-alpha which was undetectable after more than 24 hours, peak levels of IL-1 beta and IL-6 were still present at 24 hours. After incubation of the enzyme solution for some hours at 56 degrees C the cytokine inducing capacity disappeared. Neutralization experiments with inactivating antibodies, radioimmunoassay, and western blotting after electrophoretic separation showed that the TNF-like activity found in the lytic assay was due to TNF-alpha. Interferon-alpha (IFN-alpha) and Interferon-gamma (IFN-gamma), which had no effect alone, synergistically increased TNF-alpha production when applied together with the enzymes. A commercial mixture of these enzymes (Wobenzym), which was also investigated, showed a similar concentration and time dependence, as well as synergism with the interferons. A synergistic effect on TNF-alpha production was also found with the enzymes and phorbol ester (PMA).
Article
Method: In an open case observation study involving patients with blunt injuries to the musculoskeletal system, the efficacy and tolerability of high-dose Bromelain POS, a plant-derived enzyme preparation, were investigated. The investigating physician was an orthopedic surgeon who, in addition to the usual therapeutic measures, treated 59 of his patients with the bromelaine preparation. The duration of the application was determined by the nature and severity of the lesion, and varied between one and three weeks. The test criteria were swelling, pain at rest and during movement, and tenderness. These parameters were evaluated on the day of the injury and on five subsequent dates. Results: Treatment with bromelaine resulted in a clear reduction in all four parameters tested. Both swelling and the symptoms of pain had improved appreciably at all evaluation time points as compared with baseline. The tolerability of the preparation was very good, and patient compliance was correspondingly high.
Article
Pharmaceutical preparations containing mixtures of various proteolytic and nonproteolytic enzymes have been suggested for use in the treatment of malignant diseases. However, the mode of action of such preparations was not clear. We have shown before that intact bromelain, papain or amylase, which are components of a commercial polyenzyme preparation, induce cytokine production in peripheral blood mononuclear cells in vitro. IFN-alpha and IFN-gamma which had no effect alone, synergistically increased TNF production when applied together with the enzymes. Here we show that trypsin alone had only a small inducing effect. The tryptic but not the autolytic fragments of papain and bromelain have a higher (10- to 40-fold) inducing capacity for TNF production than the untreated enzyme. Additionally we demonstrate that after ingestion of milligram doses of the polyenzyme preparation (as recommended for clinical use), PBMNC of healthy donors acquire the ability to produce TNF-alpha, IL-1 beta and IL-6 when incubated ex vivo with IFN-gamma. Our results indicate that the biological effects observed after oral administration of polyenzyme preparations are related to their ability to induce cytokine production. This may explain the antitumor effects of such enzymes. Our results also suggest that polyenzyme preparations may have a stronger immunomodulary effect when used in combination with IFN-gamma.
Article
Crude bromelain extracts from pineapple stems (Ananas comosus) were fractionated by two-step FPLC-cation-exchange chromatography. At least eight basic proteolytically active components were detected. The two main components F4 and F5 together with the most active proteinase fraction F9 were characterized by SDS-PAGE, mass spectroscopy, multizonal cathodal electrophoresis, partial amino acid sequence, and monosaccharide composition analysis. F9 amounts to about 2% of the total protein and has a 15 times higher specific activity against the substratel-pyroglutamyl-l-phenylanalyl-l-leucine-p-nitroanilide (PFLNA) than the main component F4. The molecular masses of F4, F5, and F9 were determined to 24,397, 24,472, and 23,427, respectively, by mass spectroscopy. Partial N-terminal amino acid sequence analysis (20 amino acids) revealed that F9 differs from the determined sequence of F4 and F5 by an exchange at position 10 (tyrosine→serine) and position 20 (asparagine→ glycine). F4 and F5 contained fucose, N-acetylglucosamine, xylose, and mannose in ratio of 1.0∶2.0∶1.0∶2.0, but only 50% of the proteins seem to be glycosylated, whereas F9 was found to be unglycosylated. Polyclonal antibodies (IgG) against F9 detected F4 and F5 with tenfold reduced reactivity. ThepH optimum of F4 and F5 was betweenpH4.0 and 4.5 and for F9 close to neutralpH. The kinetic parameters for PFLNA hydrolysis were similar for F4 (K m 2.30 mM,k cat 0.87 sec−1 and F5 (K m 2.42 mM,k cat 0.68 sec−1), and differed greatly from F9 (K m 0.40 mM,k cat 3.94 sec−1).
Article
Ole e 1, the major allergen from olive pollen, is a glycoprotein containing a single Asn-linked glycan moiety. Rabbit antiserum against this protein has been obtained; and its immunologic cross-reactivities in Western blotting with ascorbate oxidase, horseradish peroxidase, bromelain, ovalbumin, and honeybee venom phospholipase A2 have been studied. Ascorbate oxidase, peroxidase, and bromelain are recognized by the Ole e 1 antiserum. When these three proteins are deglycosylated by periodate treatment, such an immunologic reaction does not occur. The relative affinities of these proteins have been analyzed by direct and inhibition ELISA experiments. A commercially available antibody against horseradish peroxidase has also been considered in these studies. This antibody reacts with Ole e 1 but not with the periodate-deglycosylated allergen. Horseradish peroxidase, bromelain, and ascorbate oxidase are recognized by the IgE of sera from patients who are hypersensitive to olive tree pollen. This binding is also abolished by periodate treatment. The results are interpreted in terms of the presence of an epitope in the carbohydrate moiety of Ole e 1, which would contain a xylose involved in recognition by both IgE and IgG antibodies.
The absorption of tetracyclin in conbination with bromelain by oral application
  • G Renzinni
  • Varengo
Renzinni G, Varengo M. The absorption of tetracyclin in conbination with bromelain by oral application. Arzneim-Forsch
Influence of bromelain on penetration of antibiotics in uterus, salpinx and ovary
  • M Luerti
  • Vignali
Luerti M, Vignali ML. Influence of bromelain on penetration of antibiotics in uterus, salpinx and ovary. Drugs Expt Clin Res 1978;4:45-48.
Decrease of the incidence of coronary heart infarct by Mg-and K-orotate and bromelain
  • Ha Nieper
Nieper HA. Decrease of the incidence of coronary heart infarct by Mg-and K-orotate and bromelain. Acta Med Empirica 1977;12:614-618.
Tierexperimentelle untersuchungen zur enzymatischen lokalbehandlung subdermaler verbrennungen mit bromelain
  • P Klaue
  • G Dilbert
  • G Hinke
Klaue P, Dilbert G, Hinke G, et al. Tierexperimentelle untersuchungen zur enzymatischen lokalbehandlung subdermaler verbrennungen mit bromelain. Therapiewoche 1979;29:796-799.
Effect of bromelain on serum and tissue levels of amoxycillin
  • S Tinozzi
  • Venegoni
Tinozzi S, Venegoni A. Effect of bromelain on serum and tissue levels of amoxycillin. Drugs Expt Clin Res 1978;4:39-44.
Anti-cancer therapy with bromelain
  • G Gerard
Gerard G. Anti-cancer therapy with bromelain. Agress 1972;3:261-274.
Bromelain: A proteolytic enzyme and its clinical application Effect of oral bromelain on blood pressure and heart rate of hypertensive patients
  • Sj Taussig
  • Mm Yokoyama
  • N Chinen
Taussig SJ, Yokoyama MM, Chinen N, et al. Bromelain: A proteolytic enzyme and its clinical application. HirJ Med Sci 1975;24:185-193. 52. Gutfreund A, Taussig S, Morris A. Effect of oral bromelain on blood pressure and heart rate of hypertensive patients. Haw Med Jour 1978;37:143-146.