Stem Bromelain Proteolytic Machinery: Study of the Effects of its Components on Fibrin (ogen) and Blood Coagulation

Azarkan, Mohamed; Gonzalez, Mariana M.; Esposito, Rafaèle Calvo; Errasti, María Eugenia

doi:10.2174/0929866527666200525163622

Cited by 11 publications

(7 citation statements)

References 41 publications

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“…Of interest, Metzig et al [ 30 ] showed that incubation with bromelain completely prevents the thrombin-induced aggregation of platelets. Furthermore, in high doses, the enzyme complex downregulates both the external and internal pathways of the blood clotting system, inhibits fibrin synthesis and increases serum fibrinolytic activity [ 10 , 34 ]. Taken together, all these bromelain effects may contribute to the prevention of microthrombi and, thus, to the improved perfusion of the flap tissue.…”

Section: Discussionmentioning

confidence: 99%

“…In all these cases, orally administered bromelain could reduce pain and swelling and facilitate faster healing [ 6 , 8 ]. The possible mechanisms mediating these beneficial effects are the dose-dependent modulation of bradykinin secretion [ 9 ], an improved microcirculatory flow due to the fibrinolytic and anticoagulant activity of the enzymes [ 10 ], the downregulation of inflammatory mediators [ 11 ] and the modulation of leukocyte–endothelial cell interactions [ 12 ]. Interestingly, bromelain has also been shown to protect hepatocytes from apoptosis after warm ischemia [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Bromelain Protects Critically Perfused Musculocutaneous Flap Tissue from Necrosis

et al. 2022

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Bromelain has previously been shown to prevent ischemia-induced necrosis in different types of tissues. In the present study, we, therefore, evaluated for the first time, the tissue-protective effects of bromelain in musculocutaneous flaps in mice. Adult C57BL/6N mice were randomly assigned to a bromelain treatment group and a control group. The animals were treated daily with intraperitoneal injections of 20 mg/kg bromelain or saline (control), starting 1 h before the flap elevation throughout a 10-day observation period. The random-pattern musculocutaneous flaps were raised on the backs of the animals and mounted into a dorsal skinfold chamber. Angiogenesis, nutritive blood perfusion and flap necrosis were quantitatively analyzed by means of repeated intravital fluorescence microscopy over 10 days after surgery. After the last microscopy, the flaps were harvested for additional histological and immunohistochemical analyses. Bromelain reduced necrosis of the critically perfused flap tissue by ~25%. The bromelain-treated flaps also exhibited a significantly higher functional microvessel density and an elevated formation of newly developed microvessels in the transition zone between the vital and necrotic tissues when compared to the controls. Immunohistochemical analyses demonstrated a markedly lower invasion of the myeloperoxidase-positive neutrophilic granulocytes and a significantly reduced number of cleaved caspase 3-positive apoptotic cells in the transition zone of bromelain-treated musculocutaneous flaps. These findings indicate that bromelain prevents flap necrosis by maintaining nutritive tissue perfusion and by suppressing ischemia-induced inflammation and apoptosis. Hence, bromelain may represent a promising compound to prevent ischemia-induced flap necrosis in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bromelain Protects Critically Perfused Musculocutaneous Flap Tissue from Necrosis

et al. 2022

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“…Another occasionally assumed effect traced back to the application of ED is the occurrence of (mild) coagulopathy, which is also reflected by safety notes of drug approval [63,74]. The enzyme bromelain has been associated with coagulation abnormalities in in vitro and in vivo experiments, as well as after oral medication [104][105][106][107]. A case report of Martìn et al has already drawn attention to this subject in case of topical ED using a bromelain-based approach in burn injuries [108].…”

Section: Results and Advantagesmentioning

confidence: 99%

Role, Development, and Value of Enzymatic Debridement as Integral Component in Initial Treatment of Burn Injuries Exemplified by NexoBrid®

Mattern

Fuchs

Schiefer

2022

EBJ

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Despite intensive research and increased knowledge over the past decades, the handling of severe burn injuries remains complex and is mainly based on clinical experience. High demands in terms of the diagnosis and choice of therapy often confront clinicians with challenging circumstances. Thus, the treatment of burn injuries has predominantly remained under the responsibility of specialised centres. As a new approach in addition to conventional surgery, enzymatically controlled debridement has come into focus for the treatment of burn injuries over the past years. The efficacy and safety of enzymatic debridement has already been implemented by numerous reputable studies. Promising results from the literature are enhanced by feedback from various conference contributions, intradisciplinary exchanges, and international collaborations. The implementation of enzymatic debridement in initial care management was found to be capable of reforming Standards of Care in numerous burn centres by facilitating treatment determinations and reducing the number of classical surgical interventions. Nevertheless, its use is also subject to certain restrictions as usage has shown limitations concerning efficacy when applied to scalds or pre-treated wounds. Enzymatic debridement shows high efficacy in terms of tissue debridement by combining this feature with the minimisation of collateral damage and a broad field of application in burn injuries. Due to their impressive performance in the treatment of burn injuries, enzyme-based techniques have also attracted attention for the treatment of other pathologies such as chronic wounds and are objects of ongoing research in this field. In this article, we illustrate the significance of enzyme-based treatment in initial burn care and shed some light on the potential value of enzymatic approaches in future burn surgery.

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“…Bromelain, a complex mixture of proteolytic cysteine proteases obtained from stem of pineapple (Ananas comosus) is a food supplement exhibiting a variety of pharmacological activities. Various studies substantiate the bromelain's mucolytic [13], wound healing [14], fibrinolytic [15], antiedematous [16], antithrombotic [17], anti-inflammatory [18], antioxidant [19], anticancer [20] as well as immunomodulatory activity [21]. Bromelain significantly decreases COX-2 and PGE-2 expression and lower the cytokines (IL-1β, IL-6 and TNF-α) secretion from immune cells in inflammatory conditions [22,23].…”

Section: Introductionmentioning

confidence: 94%

Implications of nasal delivery of bromelain on its pharmacokinetics, tissue distribution and pharmacodynamic profile—A preclinical study

Sharma

Gupta²,

Pandey³

2022

PLoS ONE

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Asthma is a polygenic chronic inflammatory respiratory disease devastating the quality of life and state economies. Therefore, utilization of natural products as a therapeutic approach has attained wider consideration for development of novel drugs for asthma management. Bromelain, a mixture of natural bioactive cysteine proteases abundantly found in pineapple stem, has allured attention for its pharmacological activities. However, poor stability in gastric milieu, high dose and immunogenicity associated with prolonged use hinders its oral use. Therefore, need exists to explore alternative route of bromelain administration to achieve its plausible benefits. The present study investigated the preclinical prospects of nasal administration of bromelain on systemic bioavailability, tissue distribution and it’s in vivo anti-histaminic, bronchodilator and anti-asthmatic activity in animal models. Pharmacokinetic studies revealed 1.43-fold higher relative bioavailability with faster absorption of bromelain on nasal administration at one-fourth oral dose. The enhanced cellular uptake and localization of bromelain in tissues of lung was observed significantly. Furthermore, faster onset and enhanced antihistaminic, bronchodilator and anti-asthmatic activity on bromelain’s nasal administration signified faster absorption and higher in vivo stability of bromelain. Nasal administration significantly achieved decrease in level of oxidative and immunological markers along with restoration of antioxidant enzymes at considerably one-fourth dose administered orally. These findings distinctly manifested that nasal administration could be a substantial and effective route for bromelain delivery with enduring competency in asthma management.

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Stem Bromelain Proteolytic Machinery: Study of the Effects of its Components on Fibrin (ogen) and Blood Coagulation

Cited by 11 publications

References 41 publications

Bromelain Protects Critically Perfused Musculocutaneous Flap Tissue from Necrosis

Bromelain Protects Critically Perfused Musculocutaneous Flap Tissue from Necrosis

Role, Development, and Value of Enzymatic Debridement as Integral Component in Initial Treatment of Burn Injuries Exemplified by NexoBrid®

Implications of nasal delivery of bromelain on its pharmacokinetics, tissue distribution and pharmacodynamic profile—A preclinical study

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