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Bromelain: A Literature Review and Discussion of its Therapeutic Applications
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)
... Bromelain is a mixture of different thiol endopeptidases and other components peroxidases, phosphatases, cellulases, carbohydrates, several protease inhibitors and organically bound calcium [8,9]. Fruit bromelain and stem bromelain possess different biochemical properties and compositions when compared. ...
... Bradykinin is a mediator of inflammation, where it stimulates both pain and vascular permeability, causing them to increase. The clotting cascade will convert fibrinogen to fibrin, a protective matrix around the injury that inhibits tissue drainage, promotes edema, and blocks blood flow [8] as illustrated in Figure 8. ...
... Overview of Kinin system and clotting cascade[8] ...
Bromelain is a proteolytic enzyme derived from the pineapple plant (Ananas comosus). Bromelain can be extracted from pineapple stems and fruits. Additionally, it can be derived from pineapple wastes such as the core, crown, and peel. Various extraction and purification methods such as reverse micellar system, aqueous two-phase system, chromatographic techniques, and membrane filtration have been used in order to produce high-quality bromelain. Bromelain has been used clinically since 1876 and was first introduced as a therapeutic agent in 1957. Bromelain has gained increasing acceptance and compliance among patients as a phytotherapeutic drug due to its safety and lack of undesirable side effects. Bromelain is regarded as a nutrient that promotes wound healing due to the presence of several closely related proteinases that exhibit anti-inflammatory, fibrinolytic, and debridement properties.
... 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. ...
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.
... Physiologic actions of bromelain include: anti-inflammatory action, smooth muscle relaxation, inhibition of blood platelet aggregation, improved wound healing, and when taken with meals, enhanced digestion. [28][29][30][31][32][33][34][35][36][37][38] Several mechanisms may account for bromelain's widely utilized anti-inflammatory effects: 1) enhanced proteolytic activity at sites of inflammation; 2) fibrinolysis activity via the plasminogen-plasmin system; 3) depletion of kininogen; and 4) inhibition of biosynthesis of pro-inflammatory prostaglandins and induction of PGE-1 accumulation. 29,31,32,38 While bromelain has been demonstrated to be absorbed intact (up to 40% of ingested amount), the proteolytic actions are inhibited by serum factors, 31,32 suggesting that the first mechanism has only limited effect under normal circumstances. ...
... [28][29][30][31][32][33][34][35][36][37][38] Several mechanisms may account for bromelain's widely utilized anti-inflammatory effects: 1) enhanced proteolytic activity at sites of inflammation; 2) fibrinolysis activity via the plasminogen-plasmin system; 3) depletion of kininogen; and 4) inhibition of biosynthesis of pro-inflammatory prostaglandins and induction of PGE-1 accumulation. 29,31,32,38 While bromelain has been demonstrated to be absorbed intact (up to 40% of ingested amount), the proteolytic actions are inhibited by serum factors, 31,32 suggesting that the first mechanism has only limited effect under normal circumstances. The latter three mechanisms are closely interrelated, since after tissue injury, the kinin, complement, fibrinolytic and clotting systems are all activated. ...
Carpal tunnel syndrome (CTS) is a neuropathy caused by entrapment and compression of the median nerve as it passes through the carpal tunnel in the wrist, leading to a decrease in nerve transmission to and from the hand. Symptoms include pain, numbness, tingling, aching, and loss of motor and sensory function in the first three digits of the hand. These symptoms are typically worse at night and can awaken the individual. CTS is more common in women than men, and is a common occurrence in occupations involving repetitive motions of the upper extremity. A vitamin B6 deficiency has been found in many patients with CTS, and treatment with B6 or its bioactive form, pyridoxal 5' phosphate, is helpful in the majority of cases. Addressing the individual's occupational biomechanical and/or ergonomic factors, in addition to manual manipulation and the therapeutic use of anti-inflammatory substances such as bromelain can be of significant benefit and may decrease the need for carpal tunnel release surgery. (Alt Med Rev 1997;2(1):26-35)
... In addition to the blockage of arachidonic acid cascade at the enzyme cyclooxygenase, bromelain may selectively decrease thromboxane generation and shift the ratio of thromboxane/ prostacyclin (PGI2) in favor of prostacyclin [22].At inflammation site, a dose dependent reduction of bradykinin and prekallikrein levels were seen after administration of bromelain. Bromelain thereby prevents the production of oedema and decreases the severity of existing oedema [23]. ...
... Bromelain injection resulted in a dose-dependent decrease in serum fibrinogen levels in rats. Both prothrombin time (PT) and activated partial thromboplastin time (APTT) are considerably prolonged when larger quantities of bromelain are given [23]. ...
This review focused on the usage of bromelain in numerous applications, as well as the most recent literature on the chemistry, extraction, and purification of bromelain from pineapple (Ananas comosus). Bromelain is a crude, aqueous extract obtained from the stems and fruits of pineapple, leading edible member of the family Bromeliaceae. Bromelain contains a mixture of different thiol endopeptidases as well as phosphatases, glucosidases, peroxidases, cellulases, & glycoproteins. It exerts its enzymatic activity over a PH range 4.5 – 9.5. The isolation & purification of bromelain has been done by various methods includes aqueous two-phase extraction, reverse micellar extraction, ultrafiltration & precipitation & chromatographic techniques. Bromelain, a cysteine protease, has found commercial use in a variety of industries including food, beverage, tenderization, cosmetic, pharmaceutical, and textile. Bromelain act as an immunomodulatory, anti-inflammatory agent, anti-oedematous, anti-thrombotic & anti-metastatic. Although the precise mechanism of action of bromelain has not been established, bromelain has received widespread acceptance as a phytotherapeutic agent due to its long history of safety and absence of adverse effects
... 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). ...
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.
... 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]. ...
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.
... 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. ...
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.
... [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. ...
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
... 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. ...
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.
... Bromelain is a natural blend of proteolytic enzymes generated from both stem and fructus of the pineapple (Ananas comosus) plant that prevents the spread of inflammation by blocking proinflammatory metabolites. Bromelain is commonly used to treat arthritis, trauma, and other inflammatory processes [6,7]. It reduces the interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) secretion when immune cells caused by inflammation are already stimulated by the overproduction of cytokines [8]. ...
Purpose:
Several substances that have anti-inflammatory, antiproteinase, and anti-infective properties have been evaluated as modulators of the inflammatory response in periodontal disease. However, evidence for the anti-inflammatory and antioxidative activities of bromelain is limited. This study evaluated the impact of systemically administered bromelain on the progression of experimental periodontitis.
Methods:
Four equal groups of 32 Wistar albino rats were created as follows (n = 8): control, periodontitis + saline, periodontitis + 5 mg/kg/day bromelain, and periodontitis + 10 mg/kg/day bromelain. To quantify the resorption of bone and bone volume/tissue volume, bone surface / bone volume, and connectivity, lower jawbones were fixed and then scanned using microcomputed tomography (micro CT). Blood samples were taken to measure the macrophage colony-stimulating factor(M-CSF) concentrations, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-8 (MMP-8), interleukin-6(IL-6), glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological assessments were made to examine the tissue.
Results:
Treatment with bromelain improved the healing of the periodontium by decreasing the number of leukocytes and ligament deterioration in the gingival connective tissue and by supporting reintegration with alveolar bone. Bromelain used in ligature-induced periodontitis reduced alveolar bone (AB) resorption as measured by microCT; reduced inflammatory parameters such as IL-6 and TNF-α; regulated oxidative-antioxidative processes by increasing GPx and SOD and reducing MDA levels; and regulated AB modeling by decreasing M-CSF, RANKL, and MMP-8 and increasing OPG levels.
Conclusion:
Bromelain may be an option in periodontal therapy by regulating cytokine levels, improving the healing process, and reducing bone resorption and oxidative stress.
... According to the composition of physicochemical and nutritional values such as bromelain, organic acids, antioxidants and phenolic compounds, pineapple can be considered one of the most useful fruits in producing value-added substances (Ali et al., 2020). Pineapple by-products are an abundant source of bromelain (proteolytic sulfhydryl enzymes) belonging to the family of proteindigesting enzymes that can be extracted from pineapple in several native cultures (Gregory and Kelly, 2016). Bromelain is a pricey combination of proteolytic enzymes with various biological properties that are utilized in the pharmaceutical, culinary, and cosmetic industries (Ramli et al., 2017). ...
The study on the antibacterial activity of fruit, peel, stem, and core of the pineapple, Ananas comosus crude extract against Aeromonas hydrophila and the effect of supplementing the diet with pineapple waste crude extract on growth performance and resistance against A. hydrophila in Nile tilapia, Oreochromis niloticus were conducted. The best result of antibacterial screening was performed by disc method and the minimum inhibitory concentration was found in pineapple fruit extract with an inhibition zone of 7.96±0.20 mm and the minimum inhibitory concentration value was 125 mm per liter. The minimum bactericidal concentration value was not observed in all parts of thespineapple extract at any concentration. Furthermore, Nile tilapia (2.34±0.82 g) were stocked in 12 aquaria and fed a diet supplemented with 4 different doses of pineapple peel extract (0, 1, 2 and 3%) for 8 weeks. The results revealed that the best value of weight gain, average daily weight gain, specific growth rate, feed conversion ratio, protein efficiency ratio and feed utilization efficiency was observed in fish fed 1% pineapple peel extract and additionally, the mortality of fish challenged by Aeromonas hydrophila was recorded for 10 days after the challenge. The result showed that fish-fed diet containing 1% pineapple peel extract had significantly the lowest mortality and the highest relative survival percentage.
... Several enzymes, notably bromelain, are produced by the pineapple plant (Ananas comosus) and utilized commercially for protein digestion [1][2][3] . It is a nontoxic chemical with therapeutic effects for modulation. ...
Objective:
In the present study, we investigated the topical bromelain's cytotoxic effects on mouse fibroblast NIH/3T3 cells via cell culture study.
Materials and methods:
In this cell culture study, Dulbecco's Modified Eagle Medium (DMEM) with fetal bovine serum (FBS, 10%) and penicillin/streptomycin (1%) was used as a cell growth medium for NIH/3T3 mouse fibroblast cells. MTT test was performed in 96-well plates seeded with NIH/3T3 cells 5x103/well and under standard cell culture conditions. Bromelain doses of 3.13 to 100 μM were administered to the wells and incubated for 24, 48, and 72 hours in the same cell culture conditions. For Confocal microscopic evaluation, NIH/3T3 cells were plated on cover slips in 6-well plates (105 cells/well) and treated with 100 μM concentration of bromelain for 24 h. Untreated cells were used as controls.
Results:
MTT results showed that bromelain is not cytotoxic on mouse fibroblast NIH/3T3 cells. All three incubation times of 24, 48, and 72 hours bromelain initiated cell growth. A statistically significant rise in cell growth was detected in the only applied highest dose of 100 μM bromelain for all incubation times except for 24 hours. The nontoxic effect was further investigated by using confocal microscopy by applying the highest bromelain dose of 100 μM to NIH/3T3 mouse fibroblast cells. Confocal micrographs showed that bromelain did not change the morphology of mouse fibroblast cells at the incubation time of 24h. In untreated cells and bromelain-treated cells, the nucleus of NIH/3T3 cells was undamaged and compact, and the cytoskeleton was fusiform and non-fragmented.
Conclusions:
Bromelain is not cytotoxic on mouse fibroblast NIH/3T3 cells and enhances cell growth. If clinical trials will confirm this, it is possible that bromelain will be used topically in humans to enhance wound healing, in rhinosinusitis and chronic rhinosinusitis with nasal polyps and endonasal surgeries due to its anti-inflammatory effects.
... Two main categories of bromelain are available "stem bromelain" (EC 3.4.22.32) and "fruit bromelain" (EC 3.4.22.3) isolated from the stem and from its juice, respectively (Kelly 1996). Bromelain is useful in the leather industry for animal skin softening, pre-tanning, and food and therapeutics. ...
Reduction of food waste by extensively using raw sources builds good impact on the climate, environment, and food security. Fruits and vegetables are the commodities of horticultural crops that are commonly used. Thus, the waste generated during processing can be proclaimed as a valuable by-product if extensive technological interventions are used to improve the value of successive goods to balance the cost of processing. Fruit and vegetable wastes have great potential for bioconversion into valuable products with biotechnological, biocontrol, bioenergy, and industrial applications. These wastes could serve as a source of edible coating, fat mimetics, fortified probiotics, natural pigment, and volatile compounds in the food industry. Additionally, these wastes can also be used for synthesizing green carbon dots, biochar, and biosorbents that have environmental applications. The utilization of these fruit and vegetable wastes for generating valuable products is a foundation step towards sustainable development. The current chapter discusses the valuable products that can be obtained by bioconversion of waste of fruits and vegetables by enlisting their application in both food and environmental sectors.
... Two main categories of bromelain are available "stem bromelain" (EC 3.4.22.32) and "fruit bromelain" (EC 3.4.22.3) isolated from the stem and from its juice, respectively (Kelly 1996). Bromelain is useful in the leather industry for animal skin softening, pre-tanning, and food and therapeutics. ...
Agricultural residues, including fruit and vegetable residues, which usually contain starch or cellulose, are used for bioconversion into value-added products. Bioconversion provides several advantages, such as high value considering their material and energy recovery, decrease in landfill areas, lower cost of the technology, and the farmers’ income. Bioprocessing is of great importance for horticultural waste management to satisfy the needs of developing countries. Fermentation (solid-state and submerged) is considered an important tool to increase the nutritional value (providing more proteins, amino acids, and other biomolecules) of SCP and aquafeed meal ingredients. This chapter investigates the role of fruit and vegetable wastes in the production of single-cell protein (SCP) and aquafeed meal.
... 38 Recommended doses range from 500 to 2000 mg per day. 39 Cineole Cineole, or more specifically 1,8-cineole, is a monoterpene present in many plantbased essential oils and is commonly derived from Eucalyptus globulus. It has been shown to reduce mucus production, block inflammation through inhibiting cytokines tumor necrosis factor (TNF)-a and interleukin (IL)-1b, and produce antinociceptive effects. ...
Rhinosinusitis is characterized by inflammation of the mucosa involving the paranasal sinuses and the nasal cavity and is one of the most common and significant health care problems, with significant impairment of quality of life. Current standard conventional management of rhinosinusitis commonly uses multiple therapeutic modalities to break the cycle of chronic disease. However, to date, there is no consensus as to the optimal treatment algorithm for patients with chronic rhinosinusitis. There is a growing interest in the use of complementary and integrative medicine for the treatment of rhinosinusitis. This article update focuses on an integrative approach to rhinosinusitis.
... Bromelain is known to possess antiinflammatory activity and has been shown to reduce blood viscosity, prevent the aggregation of blood platelets, and improve ischemia/reperfusion (I/R) injury in a skeletal muscle model (Juhasz et al. 2008). Bromelain acts on fibrin to facilitate fibrinolysis, thus helping to dissolve the clot and minimize the risk of arterial thrombosis (Taussig 1980;Kelly 1996). A recent study reported that bromelain is a potent anti-inflammatory compound evaluated against wound in rats (Fathi et al. 2020). ...
Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) – induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.
... Flies fed with C. quadrangularis extract exhibited more blue dye in their abdomen region revealing the more food intake influenced by orexigenic property of the plant. Similarly, flies fed food media without C. quadrangularis stem extract shown lesser blue dye uptake.The amount of food intake was measured by quantitating the dye via spectrophotometry (Fig. 8 Kelly, 1996). In this study, protease activity of C. quadrangularis stem extract revealed total activity as 975 U/ml and specific activity as 3768 U/mg. ...
Plants with diverse pharmacological activities are actively being explored for human health. Cissus quadrangularis (L) has been reported to possess numerous phytochemicals and is used to relieve various disorders. This article aims at providing evidence of the diverse pharmacological activities in terms of orexigenic, anti-inflammatory, anti-diabetic and antioxidant activities of C. quadrangularis for further application in clinical development. The results revealed that inhibition of hemolysis was within the range of 8-9-25.6% at concentrations of 12.5-200 µg/ml. Methanol extract of C. quadrangularis stems exhibited porcine pancreatic ?-amylase (PPA) inhibition (p?0.05) at concentrations of 0.25 and 0.30 mg/ml. The glucose adsorption capacity of the C. quadrangularis was observed to be inversely proportional to the molar concentration of glucose. The higher food intake by Drosophila in food medium with plant extract is presumably related to orexigenic property of C. quadrangularis. Protease activity of C. quadrangularis stem extract revealed total activity 975 U/ml and specific activity as 3768 U/mg. The absorbance of C. quadrangularis in reducing power assay were between 0.91and 1.85. Highest total antioxidant activity of 67.2 µg TE/g was observed and the hydroxyl radicals scavenging activity was observed in a dose dependent manner. The results provide supporting data that C. quadrangularis may contain active compounds useful in treating anti-inflammatory, anti-diabetic disorders.
... 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. ...
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. ...
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]. ...
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.
... 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). ...
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.
... 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. ...
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.
... 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. ...
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.
... 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). ...
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.
... 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). ...
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.
... 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]. ...
... 4 The other substances typically include peroxidase, acid phosphatase, protease inhibitors and calcium. 5,6 Absorption and Bioavailability ...
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.
... 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 . ...
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.
... 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. ...
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.
... 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). ...
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
... 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). ...
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 (H2S) 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 H2S in growing–finishing pigs.
... 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. ...
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.
Tannin acyl hydrolase is also known as tannase. Tannase acts upon
ester and depside linkages in gallotannins,ellagitannins, complex
tannins and gallic acid esters to gallic acid that finds application in
the food processing industry due to its antioxidant activity. Tannins are present in every part of plant in the form of secondary metabolite. The animal sources of tannase include bovine intestine and ruminal mucus. Although tannase has a long history with numerous publications, it is still considered as an expensive industrial enzyme. Tannase derived from microorganisms have wide applications in various industries, due to their abundance and ease to produce. Organisms like bacteria, fungi and yeast produce tannase enzyme which can be used for various applications. The fungi isolated from various sources produce more tannase enzyme. There are various fermentation and purification processes to produce tannase enzyme using microorganisms.It is extensively used in food, animal feed,
pharmaceutical, beverage, brewing, tannery and chemical industry. Main application of tannase is elaboration of instantaneous tea, acorn wine and gallic acid production. It is also used as clarifying agent in juice and coffee flavored beverages. Gallic acid is used in pharmaceutical industry as an intermediary compound for the synthesis of trimethoprim antibiotic. In chemical industry it is used as substrate for the chemical or enzymatic synthesis of propylgallate and other antioxidant compounds used in food processing industry. This chapter deals about the application of tannase in various fields.
Keywords:Tannase, Tannin, Gallic acid, Food Industry, Pharmaceutical, Brewery, Tannery.
The authors were not aware of errors made in one small subsection (Section 6.17. Antidiarrheal Effect, including the data in the table of effects) of this paper [...]
Background
Tendinopathy refers to conditions characterized by collagen degeneration within tendon tissue, accompanied by the proliferation of capillaries and arteries, resulting in reduced mechanical function, pain, and swelling. While inflammation in tendinopathy can play a role in preventing infection, uncontrolled inflammation can hinder tissue regeneration and lead to fibrosis and impaired movement.
Objectives
The inability to regulate inflammation poses a significant limitation in tendinopathy treatment. Therefore, an ideal treatment strategy should involve modulation of the inflammatory process while promoting tissue regeneration.
Methods
The current review article was prepared by searching PubMed, Scopus, Web of Science, and Google Scholar databases. Several treatment approaches based on biomaterials have been developed.
Results
This review examines various treatment methods utilizing small molecules, biological compounds, herbal medicine‐inspired approaches, immunotherapy, gene therapy, cell‐based therapy, tissue engineering, nanotechnology, and phototherapy.
Conclusion
These treatments work through mechanisms of action involving signaling pathways such as transforming growth factor‐beta (TGF‐β), mitogen‐activated protein kinases (MAPKs), and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), all of which contribute to the repair of injured tendons.
Basic life support (BLS) is an essential skill for saving lives. University students should be taught the knowledge essential to mastering this skill. Therefore, the attitude toward BLS would persist following BLS training. This study aims to describe the knowledge and attitudes of Indonesian professional healthcare students toward BLS courses. The participants in this cross-sectional study were health science, medical, and dental students from 22 universities in Indonesia. This study employed a 33-item validated questionnaire (20 knowledge and 13 attitude). The data were analyzed using logistic regression. A total of 1000 subjects were recruited. Females (p = 0.04; 0.55 – 1.98) linked with BLS training history (p = 0.05; 0.36 – 1.01) were found to pose an impact on BLS attitudes. Several factors such as medical faculty (p < 0.05), the BLS training method with a combination of theory and practice (p < 0.05), and the history of a family member receiving cardiopulmonary resuscitation (CPR) (p < 0.01) were independently influenced both BLS knowledge and attitudes. Numerous factors have been identified as having an impact on students’ BLS knowledge and attitudes. BLS teaching courses should be integrated into all health science curricula using a combination of theory, demonstration, and mannequin practice. The courses should be regularly updated in order to improve student proficiency.
Background:
Ananas comosus L. (Family Bromeliaceae) is a plant innate to South America and has been cultivated in various world regions. Plant parts have traditionally been used to treat various ailments like cancer, diabetes mellitus, bacterial infection, Covid 19 infection, inflammation, arthritis, asthma, malaria, cardiovascular disease, and burn as debridement agents. The pineapple contains nutrients, including vitamin C, iron, potassium, and protein. It also contains flavonoids, carotenoids, tannins, polyphenols, and alkaloids.
Methods:
An extensive literature search was conducted on Ananas comosus, using three scientific databases: PubMed, Scopus, and Web of Science. The keywords in this paper were combined to form a search strategy. Ananas comosus and pineapple were the main criteria for judging abstracts, titles, and keywords. In the full text of the paper, the secondary judgment criteria included mentioning "therapeutic potential" or "pharmacological activities". Among the 250 references in the compiled bibliography, there are original articles, books, and web addresses dating back to 2001 to 2023. A review of articles was conducted after abstracts and titles were screened, and 61 duplicate articles were deleted. In this paper, information is provided on the therapeutic potential and pharmacological actions of ananas comosus and its bioactive compounds.
Results:
In this review, therapeutic potential of A. comosus has been mentioned. The current review intends to explain an updated comprehensive overview of the versatile plant's use and its clinical trials.
Conclusion:
The plant has gained enormous perspective and increasing consideration for treating various diseases. The therapeutic potential of pineapple, its compound, extracts, and their mode of action are discussed briefly. Also, clinical trials are emphasized which are in great demand and need further in-depth investigation in the future.
In vitro and in vivo studies, bromelain has
been found to reduce obesity. Objective: Obese patients
with type 2 diabetes were studied to evaluate if a dietary
supplement (bromelain) might help them lose weight.
Methods: The effects of 8 weeks of bromelain on anthropometric
parameters, HOMA-IR, and blood levels of
fasting glucose, leptin, IL-6, and TNF-α were studied in
this randomized, single-blind, controlled trial conducted
in Iraq. 52 obese diabetic patients from Iraq (25 men
and 27 women) were randomly assigned to one of two
groups: bromelain or control. During an 8-week study,
the bromelain group was given bromelain capsules (500
mg twice daily) in addition to their prior medication, metformin
tablets (500 mg three times daily), whereas the
control group received metformin tablets (500 mg three
times daily). Results: In the bromelain group, there was a
substantial reduction in BMI, WC, WHR, HOMA-IR, serum
leptin, IL-6, and TNF-α levels after the study compared to
the baseline. The bromelain group exhibited a significant
difference in BMI, WC, HOMA-IR, leptin, IL-6, and TNF-α
blood levels when compared to the control group. The
blood levels of fasting plasma glucose (FBG) and waisthip
ratio (WHR) did not change compared to the control
group. According to the findings, bromelain may help in
the treatment of obesity, improve insulin sensitivity, and
exhibit an anti-inflammatory effect in obese diabetic patients,
implying that it may be a potential supplemental
anti-obesity medication for these individuals who warrant
further research.
Background and aims:
The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults.
Methods:
The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish.
Results:
1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated.
Conclusion:
The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated.
Annually vast quantities of waste are produced from vegetables and fruits industries – a vital food industry sector. The waste is mainly composed of peels, pomaces, rinds, and seeds. They comprise an excellent source of bioactive nutraceuticals, dietary fibers, vitamins, enzymes, peel/seed oils, pigments, polyphenols, etc. The bioactive compounds are antioxidant, anticancer, anti-inflammation, anti-allergenic, and anti-atherogenic in nature, having an encouraging effect on human healthiness. Therefore, these phytochemicals have potential applications in different industries, especially in food and pharmaceuticals, to manufacture functional foods and nutraceuticals. The current chapter discusses various types of fruit and vegetable wastes, their composition, recovery, health beneficial effect, and utilization.
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.
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.
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
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.
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.
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)
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.
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.
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.
Isolation and characterization of the platelet aggregation inhibitory factor of bromelain have been presented in this study. Commercial bromelain consists of 3 major components as demonstrated by discontinuous sodium chloride gradient chromatography through carbixymethyl-sephadex column. Fraction I constituted approximately 19% of the total fraction. This fraction had no proteolytic activity or platelet aggregation inhibiting activity, but showed peroxidatic activity. Fraction II and III, which constituted the remainder of the fraction eluted with 135 mM and 800 mM NaCl concentrations, respectively, showed both proteolytic and inhibition of platelet aggregation, but no peroxidatic activity. Immunoelectrophoresis and polyacrylamide electrophoresis showed fraction I with beta-mobility while fraction II and III demonstrated gamma-mobility. It is suggested that the proteolytic activity is associated with the inhibition of platelet aggregation, since oxidation of fractions II and III with sodium tetrathionate abolished both activities. The mechanism of inhibition of platelet aggregation by bromelain is presently unknown but may involve its influence on the prostaglandin synthetic pathway of platelets.
The 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
It has been established that a bromelain plasminogen activator will produce plasmin in rat experiments. In addition the plasmin cleaves Hageman factor in a way that leads to a strong release of kallikrein but a weak release of thrombin. A possible mechanism is suggested to explain how the body can maintain thrombin at a level too low to cause platelet aggregation but adequate to stimulate release of prostaglandins and enzymes for more than 24 hours from a single dose of the pineapple enzymes. Since bromelain therapy leads to formation of platelets with increased resistance to aggregation, it is obvious that the dominant endogenous prostaglandins being produced must be from the group that increases platelet cyclicAMP levels (prostacyclin, PGE1, etc.). The combination of fibrinolytic and antithrombic properties appear to be effective and two large scale tests on heart patients have shown a practically complete elimination of thrombosis.
The 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.
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.
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.
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).
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.
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.
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).
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.