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Wound Repair and Regeneration :... Nov 2021Chronic wounds are estimated to affect over 6 million people annually in the United States with an estimated annual cost of $25 billion. Debridement represents a key... (Randomized Controlled Trial)
Randomized Controlled Trial
Chronic wounds are estimated to affect over 6 million people annually in the United States with an estimated annual cost of $25 billion. Debridement represents a key step in their management and is considered a basic necessity to induce the functional process of tissue repair. However, there is an unmet need for an efficient rapid acting non-surgical debridement agent. Bromelain-based enzymatic debridement has been proven to provide an effective, selective and safe non-surgical debridement in deep burns. EscharEx (MediWound Ltd, Yavne, Israel), is a bromelain-based enzymatic debridement agent currently in development for chronic wounds. The aim of this study was to assess its safety and efficacy in chronic wounds. Seventy-three patients suffering from a lower extremity ulcer of diabetic/venous insufficiency/post-surgical/traumatic aetiology were enrolled in a multicentre, assessor blinded, randomized controlled trial. Patients were randomized to topical treatment by either EscharEx or its gel vehicle for up to 10 daily 4 hour applications, and then continued follow-up for up to 6 months. The EscharEx arm achieved a significantly higher incidence of complete debridement compared to the gel vehicle arm; 55 versus 29% (p = .047), thus meeting the primary endpoint of this study. The EscharEx and gel vehicle arms achieved similar reductions in wound area, non-viable tissue area and wound healing scores during the debridement period. There were no significant differences between the arms in the incidence of complete wound closure (41% in the EsxcharEx arm vs. 53% in the gel vehicle arm) and in the mean time to complete wound closure (70.0 ± 32.8 days in the EsxcharEx arm vs. 65.7 ± 38.4 days in gel vehicle arm). There were no significant safety issues and EscharEx demonstrated a favourable benefit to risk profile.
Topics: Administration, Topical; Bromelains; Burns; Debridement; Humans; Wound Healing
PubMed: 34231281
DOI: 10.1111/wrr.12958 -
Current Pharmaceutical Biotechnology 2023Bromelain is a protein digestive enzyme obtained from the extract of pineapple (steam, fruit, and leaves). It is a cocktail of several thiol endopeptidases and other...
Bromelain is a protein digestive enzyme obtained from the extract of pineapple (steam, fruit, and leaves). It is a cocktail of several thiol endopeptidases and other components like peroxidase, cellulase, phosphatase, and several protease inhibitors. It is a glycoprotein with an oligosaccharide in its molecular structure that contains xylose, fucose, mannose, and N-acetyl glucosamine. Many approaches have been used in the extraction and purification of bromelain like filtration, membrane filtration, INT filtration, precipitation, aqueous two-phase system, ion-exchange chromatography, This enzyme is widely used in the food industry for meat tenderization, baking, cheese processing, seafood processing, However, this enzyme also expands its applicability in the food industry. It is reported to have the potential for the treatment of bronchitis, surgical trauma, sinusitis, The and studies showed that it possesses fibrinolytic, antiinflammatory, antithrombotic, anti-edematous activity, The human body absorbed bromelain without any side effects or reduction in its activity. However, in some cases, it shows side effects in those patients who are allergic to pineapple. To minimize such adverse effects bromelain is immobilized inside the nanoparticles. This paper gives an overview of the production, purification, and application of this industrially important enzyme in the food and pharmaceutical industry. It also discusses the various immobilization strategies used to enhance its efficiency.
Topics: Humans; Bromelains; Proteins; Meat; Fruit; Drug Industry
PubMed: 36999703
DOI: 10.2174/1389201024666230331115338 -
BioMed Research International 2022Aluminum (Al) is an important factor in the environment as it is used in agriculture and several industries leading to hazardous effects via oxidative stress. Bromelain...
Aluminum (Al) is an important factor in the environment as it is used in agriculture and several industries leading to hazardous effects via oxidative stress. Bromelain is a cheap extract from the byproduct waste of stem. It has been used in several biological and therapeutic applications. So, this study was undertaken to assess the hepatoprotective potential of bromelain versus oxidative stress induced by aluminum chloride in rats. Results revealed that administration of AlCl reduced the body and liver weights and increased Al concentration in the blood and liver tissue. Also, AlCl caused valuable changes in hematological parameters and increased TBARS and HO concentrations in rat liver. Enzymatic (SOD, CAT, GPx, GR, and GST) and nonenzymatic (GSH) antioxidants and protein content were significantly decreased. Furthermore, alterations in liver biomarkers such as bilirubin level and enzyme activities in both serum and liver homogenate (LDH, ALP, AST, and ALT) were detected. AlCl also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1)], tumor necrosis factor-alpha (TNF-), as well as matrix metalloproteinase (MMP9), and downregulation of nuclear factor erythroid 2 (Nrf2) expression. In addition, histopathological examination showed significant variations in the liver that confirms the biochemical results. Otherwise, bromelain intake alone slumped lipid peroxidation and gotten better antioxidant status significantly. Moreover, supplementation with bromelain before AlCl intoxication restores enzymatic and nonenzymatic antioxidants as well as biochemical indices and tissue architecture with respect to the AlCl group. In conclusion, bromelain proved its remarkable protective power to abolish AlCl toxicity. So, it might represent a new strategy in the therapy of metal toxicity by its antioxidant capacity.
Topics: Rats; Animals; Aluminum; Bromelains; Antioxidants; Hydrogen Peroxide; Oxidative Stress; Liver; Inflammation
PubMed: 36452063
DOI: 10.1155/2022/5342559 -
Scandinavian Journal of Plastic and... 1969
Clinical Trial
Topics: Bromelains; Clinical Trials as Topic; Edema; Hematoma; Humans; Placebos
PubMed: 4903748
DOI: 10.3109/02844316909036691 -
Planta Medica Jun 1990Bromelain, a standardized complex of proteases from the pineapple plant, is absorbed unchanged from the intestine of animals at a rate of 40%; in animal experiments it... (Review)
Review
Bromelain, a standardized complex of proteases from the pineapple plant, is absorbed unchanged from the intestine of animals at a rate of 40%; in animal experiments it was found to have primarily anti-edema, antiinflammatory, and coagulation-inhibiting effects. These effects are due to an enhancement of the serum fibrinolytic activity and inhibition of the fibrinogen synthesis, as well as a direct degradation of fibrin and fibrinogen. Bromelain lowers kininogen and bradykinin serum and tissue levels and has an influence on prostaglandin synthesis, thus acting antiinflammatory. In in vitro and in animal studies, experimentally induced tumours could be inhibited by bromelain. Although many studies do not give extensive statistical data, the effects of bromelain in animal studies seem to be dose-dependent. Further investigations have to be carried out.
Topics: Absorption; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bromelains; Dose-Response Relationship, Drug; Edema; Molecular Structure
PubMed: 2203073
DOI: 10.1055/s-2006-960949 -
Applied Biochemistry and Biotechnology Jun 2021Cancer is a complicated long-term disease due to computable key molecular players involved in aggravating the disease. Among various kinds of cancer, hepatocellular...
Cancer is a complicated long-term disease due to computable key molecular players involved in aggravating the disease. Among various kinds of cancer, hepatocellular carcinoma (HCC) is the ninth leading cause of cancer. Recently, plant-based products are gaining a lot of attention in the field of research because of their anti-tumor properties. In our previous study, we reported based on in-silico method that bromelain, a cysteine protease extracted from the stem of the pineapple, has high binding affinity with the transcription factors p53 and β-catenin proteins which are key players in controlling the progression of hepatocellular carcinoma. Bromelain, isolated mainly from the stem of Pineapple (Ananas comosus), belongs to the family Bromeliaceae. The present study deals with preclinical analysis of bromelain as an anti-cancer agent and its intracellular effect on the expression of p53 and β-catenin protein. Our study reports cytotoxic activity, cell proliferation, migration, invasion, arrest in the S-phase, and G2/M phase in cell cycle analysis by treating with bromelain in HepG2 cell lines. We also report up-regulation of p53 protein by drug-induced impediment leading to apoptotic process in HepG2 cells and down-regulation of β-catenin protein in HepG2 cells which interferes in β-catenin/TCF-DNA interaction further, down-regulating Wnt genes and suppressing the canonical pathway. Finally, we conclude that bromelain inhibits tumorigenic potential in HepG2 cell lines.
Topics: Ananas; Antineoplastic Agents, Phytogenic; Bromelains; Carcinoma, Hepatocellular; Cell Cycle; Cytotoxins; Hep G2 Cells; Humans; Liver Neoplasms; Neoplasm Invasiveness; Tumor Suppressor Protein p53; beta Catenin
PubMed: 33735410
DOI: 10.1007/s12010-021-03505-z -
Naunyn-Schmiedeberg's Archives of... Mar 2020Derangement of electrolyte in the sensory nervous system has been attributed to the development and maintenance of hyperalgesic and allodynic symptoms in painful...
Derangement of electrolyte in the sensory nervous system has been attributed to the development and maintenance of hyperalgesic and allodynic symptoms in painful neuropathy. This study investigated the effect of bromelain on electrolyte imbalance in chronically constricted sciatic nerve of rats (a model of neuropathic pain). Forty Wistar rats, divided into five groups of eight animals each were used for this study. von Frey filaments, tail immersion and acetone spray tests were used to assessed allodynic and thermal hyperalgesic symptoms in the Wistar rats. Sodium ion (Na), potassium ion (K), calcium ion (Ca) and chloride ion (Cl) concentrations as well as sodium-potassium and calcium electrogenic pump (Na-K ATPase and Ca ATPase, respectively) activities were estimated using spectrophotometry techniques. Bromelain significantly (p < 0.05) reversed elevation of Na and Ca concentration compared with sciatic nerve chronic constriction injury (snCCI) group (35.68 ± 1.71 vs 44.46 ± 1.24 mg/ml/mg protein and 1.06 ± 0.19 vs 6.66 ± 0.03 mg/ml/mg protein, respectively). There were also significant (p < 0.05) increases in the level of K (0.84 ± 0.02 vs 0.36 ± 0.05 mg/ml/mg protein) and Cl (18.51 ± 0.29 vs 15.82 ± 0.21 mg/ml/mg protein). Bromelain reduced the activities of Ca electrogenic pumps significantly compared with snCCI. This study therefore suggests that bromelain mitigated electrolyte imbalance in chronic constricted injury of the sciatic nerve implying that this may be an important mechanism for the anti-nociceptive effect of bromelain.
Topics: Animals; Bromelains; Chronic Pain; Constriction; Dose-Response Relationship, Drug; Male; Pain Measurement; Rats; Rats, Wistar; Sciatic Neuropathy; Water-Electrolyte Balance
PubMed: 31655851
DOI: 10.1007/s00210-019-01744-w -
Georgian Medical News Jun 2021The aim of this study was to obtain a more stable and less allergic form of bromelain, an enzyme complex derived from the stem of Pineapple plant (Ananas comosus L....
The aim of this study was to obtain a more stable and less allergic form of bromelain, an enzyme complex derived from the stem of Pineapple plant (Ananas comosus L. Merr.), via chemical modification with a polysaccharide. In order to obtain purified bromelain (enriched with protein) from comercial bromelain, protein precipitation method by alcohol was used. According to our results the protein concentration after the purification was increased by about 20%. In this work, we examine the method of bromelain's chemical modification with a water-soluble, biocompatible and biodegradable natural polysaccharide - dextran, oxidized to dextran aldehyde. For the determination of the degree of bonding gel-filtration of bromelain and modified bromelain on sephadex G-75 was performed. After gel filtration of bromelain only one fraction-peak was obtained, whereas after gel filtration of modified bromelain with dextran two fraction-peaks were obtained and the degree of protein bonding with dextran was 65±5%. The method was developed both with and without the addition of cysteine. The addition of cysteine increased the activity of modified bromelain from 50±5% to 70±5%. the pH optimum for native bromelain was 7.5, whereas for modified bromelain it was shifted towards 8.5, while the temperature optimum in both cases was 60˚C. Taking into consideration the obtained results and comparing them with literary data we suggest that modified bromelain will have much potential in medical application than currently available native product. Further research is required to test the effect of this modification on bromelain's specific pharmacological and allergic properties.
Topics: Aldehydes; Ananas; Bromelains; Dextrans
PubMed: 34365448
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Feb 2023: Bromelain and ficin are aqueous extracts from fruits of and plants, used widely for medical applications. Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE,...
: Bromelain and ficin are aqueous extracts from fruits of and plants, used widely for medical applications. Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE, degrading Ang II to angiotensin 1-7 and decreasing the cellular concentration of Ang II. : In this study, we investigated the ACE2-inhibitory, antiproliferative, and apoptosis-inducing effects of ficin and bromelain on caco-2 cells. : We found that bromelain and ficin significantly reduced the viability of human colon cancer cells with IC value concentrations of 8.8 and 4.2 mg/mL for bromelain after 24 and 48 h treatments, and 8.8 and 4.2 mg/mL for ficin after 24 and 48 h treatments, respectively. The apoptosis of the caco-2 cell line treated with bromelain was 81.04% and 56.70%, observed after 24 and 48 h. Total apoptotic proportions in caco-2 cells treated with ficin after 24 and 48 h were 83.7% and 73.0%. An amount of 1.6 mg/mL of bromelain and ficin treatments on caco-2 cells after 24 h revealed a higher decrease than that of other concentrations in the expression of ACE2 protein. : In conclusion, bromelain and ficin can dose-dependently decrease the expression of ACE2 protein in caco-2 cells.
Topics: Humans; Angiotensin-Converting Enzyme 2; Bromelains; Ficain; Caco-2 Cells; Colonic Neoplasms
PubMed: 36837502
DOI: 10.3390/medicina59020301 -
International Journal of Biological... Dec 2023Bromelains are cysteine peptidases with endopeptidase action (a subfamily of papains), obtained from different parts of vegetable belonging to the Bromeliaceae family.... (Review)
Review
Bromelains are cysteine peptidases with endopeptidase action (a subfamily of papains), obtained from different parts of vegetable belonging to the Bromeliaceae family. They have some intrinsic medical activity, but this review is focused on their application (individually or mixed with other proteases) to produce bioactive peptides. When compared to other proteases, perhaps due to the fact that they are commercialized as an extract containing several proteases, the hydrolysates produced by this enzyme tends to have higher bioactivities than other common proteases. The peptides and the intensity of their final properties depend on the substrate protein and reaction conditions, being the degree of hydrolysis a determining parameter (but not always positive or negative). The produced peptides may have diverse activities such as antioxidant, antitumoral, antihypertensive or antimicrobial ones, among others or they may be utilized to improve the organoleptic properties of foods and feeds. Evolution of the use of this enzyme in this application is proposed to be based on a more intense direct application of Bromeliaceae extract, without the cost associated to enzyme purification, and the use of immobilized biocatalysts of the enzyme by simplifying the enzyme recovery and reuse, and also making the sequential hydrolysis using diverse proteases possible.
Topics: Hydrolysis; Bromelains; Peptides; Peptide Hydrolases; Endopeptidases; Protein Hydrolysates
PubMed: 37806416
DOI: 10.1016/j.ijbiomac.2023.127244