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Nutrients Nov 2021Bromelain is a major sulfhydryl proteolytic enzyme found in pineapple plants, having multiple activities in many areas of medicine. Due to its low toxicity, high... (Review)
Review
Bromelain is a major sulfhydryl proteolytic enzyme found in pineapple plants, having multiple activities in many areas of medicine. Due to its low toxicity, high efficiency, high availability, and relative simplicity of acquisition, it is the object of inexhaustible interest of scientists. This review summarizes scientific reports concerning the possible application of bromelain in treating cardiovascular diseases, blood coagulation and fibrinolysis disorders, infectious diseases, inflammation-associated diseases, and many types of cancer. However, for the proper application of such multi-action activities of bromelain, further exploration of the mechanism of its action is needed. It is supposed that the anti-viral, anti-inflammatory, cardioprotective and anti-coagulatory activity of bromelain may become a complementary therapy for COVID-19 and post-COVID-19 patients. During the irrepressible spread of novel variants of the SARS-CoV-2 virus, such beneficial properties of this biomolecule might help prevent escalation and the progression of the COVID-19 disease.
Topics: Ananas; Anti-Inflammatory Agents; Anticoagulants; Blood Coagulation Disorders; Bromelains; Cardiotonic Agents; Cardiovascular Diseases; Fibrinolysis; Humans; Neoplasms; Plant Proteins; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34959865
DOI: 10.3390/nu13124313 -
Cureus Aug 2022The commercially available protein-digesting enzyme bromelain is derived from the pineapple fruit or stem. Bromelain from fruit and stems are produced in different ways... (Review)
Review
The commercially available protein-digesting enzyme bromelain is derived from the pineapple fruit or stem. Bromelain from fruit and stems are produced in different ways and has varied enzyme compositions. "Bromelain" often refers to the "stem bromelain". Bromelain is a combination of several thiol endopeptidases and others including various protease inhibitors, glucosidase, cellulase, phosphatase, peroxidase, and escharase. Studies conducted in both the lab and on animals show that bromelain has a variety of fibrinolytic, anti-edematous, antithrombotic, and anti-inflammatory effects. The body can absorb bromelain to a significant extent without it ceasing its proteolytic activity or having any negative side effects. Numerous therapeutic advantages of bromelain include wound debridement, improved drug absorption, and the management of sinusitis, bronchitis, angina pectoris, surgical trauma, and thrombophlebitis. Additionally, it treats numerous cardiovascular conditions, diarrhoea, and osteoarthritis. Bromelain also encourages apoptotic cell death and exhibits some anti-cancerous properties. This review compiles the crucial traits, medical and dental uses of bromelain as well as its potential mechanism of action.
PubMed: 36110474
DOI: 10.7759/cureus.27876 -
Cureus Nov 2023The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or... (Review)
Review
The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term post-infection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of post-acute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.
PubMed: 38024037
DOI: 10.7759/cureus.49204 -
Viruses Mar 2021Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike...
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.
Topics: Acetylcysteine; Antiviral Agents; Bromelains; COVID-19; Drug Evaluation, Preclinical; Drug Synergism; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Inactivation; COVID-19 Drug Treatment
PubMed: 33800932
DOI: 10.3390/v13030425 -
Foods (Basel, Switzerland) Sep 2021Bromelain is a complex combination of multiple endopeptidases of thiol and other compounds derived from the pineapple fruit, stem and/or root. Fruit bromelain and stem... (Review)
Review
Bromelain is a complex combination of multiple endopeptidases of thiol and other compounds derived from the pineapple fruit, stem and/or root. Fruit bromelain and stem bromelain are produced completely distinctly and comprise unique compounds of enzymes, and the descriptor "Bromelain" originally referred in actuality to stem bromelain. Due to the efficacy of oral administration in the body, as a safe phytotherapeutic medication, bromelain was commonly suited for patients due to lack of compromise in its peptidase efficacy and the absence of undesired side effects. Various in vivo and in vitro studies have shown that they are anti-edematous, anti-inflammatory, anti-cancerous, anti-thrombotic, fibrinolytic, and facilitate the death of apoptotic cells. The pharmacological properties of bromelain are, in part, related to its arachidonate cascade modulation, inhibition of platelet aggregation, such as interference with malignant cell growth; anti-inflammatory action; fibrinolytic activity; skin debridement properties, and reduction of the severe effects of SARS-Cov-2. In this paper, we concentrated primarily on the potential of bromelain's important characteristics and meditative and therapeutic effects, along with the possible mechanism of action.
PubMed: 34681298
DOI: 10.3390/foods10102249 -
Burns : Journal of the International... Jun 2020Bromelain-based Enzymatic Debridement has been introduced as an additional concept to the burn surgeon's armamentarium and is best indicated for mid-to deep dermal burns...
INTRODUCTION
Bromelain-based Enzymatic Debridement has been introduced as an additional concept to the burn surgeon's armamentarium and is best indicated for mid-to deep dermal burns with mixed patterns. Increasing evidence has been published focusing on special regions and settings as well as on limitations of Enzymatic Debridement to improve patient care. To better guide Enzymatic Debridement in view of the increasing experience, there is a need to update the formerly published consensus guidelines with user-orientated recommendations, which were last produced in 2017.
METHODS
A multi-professional expert panel of plastic surgeons and burn care specialists from twelve European centers was convened, to assist in developing current recommendations for best practices with use of Enzymatic Debridement. Consensus statements were based on peer-reviewed publications and clinical relevance, and topics for re-evaluation and refinement were derived from the formerly published European guidelines. For consensus agreement, the methodology employed was an agreement algorithm based on a modification of the Willy and Stellar method. For this study on Enzymatic Debridement, consensus was considered when there was at least 80 % agreement to each statement.
RESULTS
The updated consensus guidelines from 2019 refer to the clinical experience and practice patterns of 1232 summarized patient cases treated by the panelists with ED in Europe (2017: 500 cases), reflecting the impact of the published recommendations. Forty-three statements were formulated, addressing the following topics: indications, pain management and anesthesia, large surface treatment, timing of application for various indications, preparation and application, post-interventional wound management, skin grafting, outcome, scar and revision management, cost-effectiveness, patient´s perspective, logistic aspects and training strategies. The degree of consensus was remarkably high, with consensus in 42 out of 43 statements (97.7%). A classification with regard to timing of application for Enzymatic Debridement was introduced, discriminating immediate/very early (≤12 h), early (12-72 h) or delayed (>72 h) treatment. All further recommendations are addressed in the publication.
CONCLUSIONS
The updated guidelines in this publication represent further refinement of the recommended indication, application and post-interventional management for the use of ED. The published statements contain detailed, user-orientated recommendations aiming to align current and future users and prevent pitfalls, e.g. for the successful implementation of ED in further countries like the USA. The significance of this work is reflected by the magnitude of patient experience behind it, larger than the total number of patients treated in all published ED clinical trials.
Topics: Bandages; Body Surface Area; Bromelains; Burns; Debridement; Europe; Humans; Practice Guidelines as Topic; Skin Transplantation; Time Factors; Wound Healing
PubMed: 32241591
DOI: 10.1016/j.burns.2020.03.002 -
Scientific Reports May 2021For centuries, bromelain has been used to treat a range of ailments, even though its mechanism of action is not fully understood. Its therapeutic benefits include...
For centuries, bromelain has been used to treat a range of ailments, even though its mechanism of action is not fully understood. Its therapeutic benefits include enzymatic debridement of the necrotic tissues of ulcers and burn wounds, besides anti-inflammatory, anti-tumor, and antioxidant properties. However, the protease is unstable and susceptible to self-hydrolysis over time. To overcome the stability issues of bromelain, a previous study formulated chitosan-bromelain nanoparticles (C-B-NP). We evaluated the optimized nanoformulation for in vitro antioxidant, cell antiproliferative activities and cell migration/proliferation in the scratch assay, comparing it with free bromelain. The antioxidant activity of free bromelain was concentration and time-dependent; after encapsulation, the activity level dropped, probably due to the slow release of protein from the nanoparticles. In vitro antiproliferative activity was observed in six tumor cell lines for free protein after 48 h of treatment (glioma, breast, ovarian, prostate, colon adenocarcinoma and chronic myeloid leukemia), but not for keratinocyte cells, enabling its use as an active topical treatment. In turn, C-B-NP only inhibited one cell line (chronic myeloid leukemia) and required higher concentrations for inhibition. After 144 h treatment of glioma cells with C-B-NP, growth inhibition was equivalent to that promoted by the free protein. This last result confirmed the delayed-release kinetics of the optimized formulation and bromelain integrity. Finally, a scratch assay with keratinocyte cells showed that C-B-NP achieved more than 90% wound retraction after 24 h, compared to no retraction with the free bromelain. Therefore, nanoencapsulation of bromelain with chitosan conferred physical protection, delayed release, and wound retraction activity to the formulation, properties that favor topical formulations with a modified release. In addition, the promising results with the glioma cell line point to further studies of C-B-NP for anti-tumor treatments.
Topics: Antioxidants; Bromelains; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chitosan; Drug Delivery Systems; Humans; Nanoparticles; Wound Healing
PubMed: 33986357
DOI: 10.1038/s41598-021-89376-0 -
American Journal of Cancer Research 2023Mucins are a significant extracellular component of neoplastic entities such as pseudomyxoma peritonei and several gastrointestinal adenocarcinomas. Mucinous tumours... (Review)
Review
Mucins are a significant extracellular component of neoplastic entities such as pseudomyxoma peritonei and several gastrointestinal adenocarcinomas. Mucinous tumours present a challenge for systemic treatments due to poor drug penetrance and increased resistance. Therefore, the development of an effective mucolytic therapy has significant therapeutic implications for these tumour types. BromAc is a novel mucolytic agent consisting of bromelain and acetylcysteine. It has demonstrated significant mucolysis and antitumour effects and for several mucinous tumours. It has also exhibited a synergistic potentiation of the effect of several cytotoxic agents on mucinous tumours in preclinical studies. Furthermore, it demonstrates locoregional safety and efficacy in animal and clinical studies. This literature review will summarise the history of BromAc for mucinous tumours, including its conception, preclinical development and , and clinical evidence. The implications of current data and directions for future research are then discussed.
PubMed: 37168359
DOI: No ID Found -
Frontiers in Oncology 2022Bromelain is a key enzyme found in pineapple (.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory,... (Review)
Review
Bromelain is a key enzyme found in pineapple (.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases.
PubMed: 36698404
DOI: 10.3389/fonc.2022.1068778