Stem bromelain


Generic Name
Stem bromelain
DrugBank Accession Number

The primary therapeutic use for which stem bromelain is currently and formally indicated is as a burn wound eschar debridement agent that has been approved by the EMA since 2012 and marketed under the brand name Nexobrid Label.

Bromelain itself belongs to a category of protein-digesting enzymes that are obtained commercially from the fruit or stem of pineapples 1. Although both fruit and stem bromelain are prepared differently and contain different enzymatic compositions, the general term bromelain typically refers to stem bromelain 1. Bromelain is consequently a composite mixture of several different endopeptidases that can facilitate many different reactions with many different substrates. This action allows bromelain to demonstrate a wide range of therapeutic benefits ranging from cardiovascular to anticancer therapy - but the specific mechanisms of action by which it can elicit these effects are currently not properly understood.

Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
Protein Structure
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
>sp|P14518|BROM2_ANACO Stem bromelain OS=Ananas comosus OX=4615 PE=1 SV=1
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  • Bromelain, stem
  • Pineapple stem bromelain



The primary medical purpose for which stem bromelain (SB) is currently indicated for is the removal of eschar in adults with deep partial- and full-thickness thermal burns Label.

Besides this official indication, however, it is also believed that SB may be used as a treatment for several other purposes as well, including cardiovascular health, osteoarthritis, autoimmunity, blood clotting, diarrhea, cancer, surgery, and debridement - although the specific mechanisms of action for these indications remain to be elucidated 1.

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Associated Therapies
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Stem bromelain is ultimately a mixture of various different thiol endopeptidases 1 that are capable of catalyzing a range of reactions on a number of different substrates, which is perhaps why stem bromelain can evidently be used as some manner of treatment in a range of therapeutic contexts. This notion is facilitated by the fact that various topical and oral administration stem bromelain preparations exist as well, further diversifying the ways in which the medication can be used. Perhaps the most important aspect of stem bromelain, however, is its ability to undergo intestinal absorption undegraded in a functionally intact form, ultimately preserving its proteolytic actions in the plasma 1,2. This kind of pharmacodynamic characteristic is another element that perhaps allows stem bromelain to remain active within the body and elicit a number of actions at several major body systems.

Mechanism of action

Stem bromelain is ultimately a mixture of a number of thiol endopeptidases and other elements including phosphatases, glucosidase, peroxidases, cellulases, glycoproteins, carbohydrates, and various protease inhibitors 1. The many different substrates and reactions that these varied enzymes can catalyze results in a number of different and possible mechanisms of action.

Stem bromelain is currently principally used as a topical agent for debridement of necrotic tissue from wounds or second to third-degree burns Label,1. As bromelain can contain escharase as one of its component enzymes, it is thought that various stem bromelain creams or gels can accelerate the healing process of wounds by facilitating the rapid removal of necrotic layers of dermis while preserving unburned/unharmed tissues 1 and/or perhaps by accelerating the recovery of blood perfusion in wound tissue, control the expression of TNF-alpha, and raise the expression of TGT-beta, as demonstrated in the pig animal model 1. This kind of enzymatic debridement is ultimately preferred to surgical debridement as physical, surgical procedures are naturally painful, non-selective, and involve the possibility of repeat or excessive anesthesia and/or bleeding 1.

With regards to cardiovascular health, certain studies suggest that stem bromelain is capable of breaking down cholesterol plaques, eliciting a strong fibrinolytic activity, and inhibiting blood platelet aggregation - all of which protect against ischemia/reperfusion injury in skeletal muscle and minimize the risk of arterial thrombosis and embolism 1. Additionally, stem bromelain has also been shown to attenuate allergic airway disease by altering CD4+ and CD8+ T lymphocyte populations - an action that may be beneficial in treating human asthma or hypersensitivity disorders 1. Finally, stem bromelain has also been used to induce cardioprotection against ischemia-reperfusion injury via the Akt/Foxo pathway in rat model myocardium 1.

In the treatment of osteoarthritis, it is believed that stem bromelain has analgesic properties which are thought to be the result of direct influence on pain mediators such as bradykinin 1. In addition, various trials suggest that the medication could be useful in reducing swelling, bruising, and pain in women having surgery like episiotomy 1. Moreover, stem bromelain may also be used for treating acute inflammation and sports injuries 1.

Furthermore, stem bromelain has also been studied as an adjuvant therapy for chronic inflammatory, malignant, and autoimmune diseases 1. Certain in vitro experiments have demonstrated that stem bromelain can modulate surface adhesion molecules on T cells, macrophages, and natural killer cells and also cause the secretion of IL-1B, IL-6, and Tumor Necrosis Factor-alpha (TNF-alpha) via peripheral blood mononuclear cells 1. The agent has also been able to block the Raf-1/extracellular-regulated-kinase-2 (ERK-2) pathways by preventing T cell signal transduction 1. In particular however, treating cells with stem bromelain decreases the activation of CD4(+) T cells and reduces the expression of CD25 1. Additionally, there is also evidence to suggest that oral therapy with stem bromelain produces certain analgesic and anti-inflammatory effects in patients with rheumatoid arthritis, which is a particularly common autoimmune disease 1.

Stem bromelain also affects blood coagulation by increasing the serum fibrinolytic ability and by preventing the synthesis of fibrin, a protein involved in blood clotting 1. In the rat animal model, the reduction of serum fibrinogen level seems to be dose-dependent when both prothrombin time and activated partial thromboplastin time become markedly prolonged at higher concentrations of administered stem bromelain 1. In vitro and in vivo studies also suggest stem bromelain can act as an effective fibrinolytic agent since it stimulates the conversion of plasminogen to plasmin, causing an increased fibrinolysis by degrading fibrin 1.

In terms of potential antimicrobial effects of stem bromelain, there are varying observations regarding its specific mechanism of action 1. When counteracting the effects of some intestinal pathogens like Vibrio cholera or Escherichia coli (whose enterotoxin causes diarrhea in animals), some studies suggest that stem bromelain interacts with intestinal secretory signaling pathways like adenosine 3':5'-cyclic monophosphatase, guanosine 3':5'-cyclic monophosphatase, and/or calcium-dependent signaling cascades 1. Conversely, other studies propose that stem bromelain supplementation can lead to antiadhesion effects which prevent E. coli bacteria from attaching to particular glycoprotein receptors on the intestinal mucosa by proteolytically modifying those receptor attachment sites 1.

Additionally, various studies have shown that stem bromelain also possesses anticancer activity. In particular, the agent has been found to increase the expression of p53 and Bax in mouse skin, both of which are well-known apoptosis activators 1. Stem bromelain can also evidently decrease the activity of cell survival regulators like Akt and Erk, therefore inducing apoptotic tumor cell death 1. Finally, stem bromelain has also been observed to downregulate NF-kB and Cox-2 expression in mouse papillomas and in models of skin tumorigenesis 1. It has also demonstrated the capability to inhibit bacterial endotoxin (LPS)-induced NF-kB activity as well as the expression of PGE2 and Cox-2 in human monocytic leukemia and murine microglial cell lines 1.


It appears that stem bromelain can be absorbed from the human gastrointestinal tract to a small but significant extent while remaining undegraded or functionally intact 1,2. In a study involving 19 healthy men, daily oral administration of 3g/day of bromelain resulted in a mean plasma concentration of approximately 5000 pg/ml by 48 hours, although the maximum peak blood concentration of bromelain varied between 2000 to 10,000 pg/ml between subjects 2. The average blood concentration of bromelain in the period range of 3 to 51 hours was 10.28 ug 2.

Volume of distribution

No readily accessible data regarding the volume of distribution of stem bromelain is available.

Protein binding

It was determined that approximately 50% of bromelain is associated with plasma proteins like alpha 2-macroglobulin and alpha 1-antichymotrypsin, which are antiproteinases found in the blood 1,2.


Given its protein structure, it is assumed that stem bromelain, when administered would experience hydrolysis in the gut or eventually in the bloodstream after absorption 2. Regardless, radiolabelled, intact stem bromelain has been found circulating in the plasma after administration 1,2.

Route of elimination

No readily accessible data regarding the route of eliminiation of stem bromelain is available.


The estimated plasma half-life of stem bromelain is 6-9 hours 2.


No readily accessible data regarding the clearance of stem bromelain is available.

Adverse Effects
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The human body can seemingly absorb significant amounts of bromelain - about 12 grams/day of bromelain may be consumed without the appearance of any major adverse effects 1. Another study suggests that after giving bromelain (3000 FIP unit/day) to human over a period of ten days discovered no significant changes in blood coagulation parameters 1. Finally, stem bromelain has a relatively low toxicity with an LD50 greater than 10 g/kg in mice, rats, and rabbits 1.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.


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International/Other Brands
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Nexobrid2 gCutaneousMedi Wound Germany Gmb H2016-09-08Not applicableEU flag
Nexobrid5 gCutaneousMedi Wound Germany Gmb H2016-09-08Not applicableEU flag


Drug Categories
Chemical TaxonomyProvided by Classyfire
Not Available
Organic Compounds
Super Class
Organic Acids
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Alternative Parents
Not Available
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

CAS number


General References
  1. Pavan R, Jain S, Shraddha, Kumar A: Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203. doi: 10.1155/2012/976203. Epub 2012 Dec 10. [Article]
  2. Castell JV, Friedrich G, Kuhn CS, Poppe GE: Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol. 1997 Jul;273(1 Pt 1):G139-46. doi: 10.1152/ajpgi.1997.273.1.G139. [Article]
PubChem Substance
FDA label
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Clinical Trials

Clinical Trials
3Active Not RecruitingTreatmentThermal Burns2
1, 2Not Yet RecruitingTreatmentAdenocarcinoma, Mucinous / Malignant Peritoneal Neoplasm / Mucinous Tumor / Pseudomyxoma Peritonei1
Not AvailableAvailableNot AvailableThermal Burn1


Not Available
Not Available
Dosage Forms
Not Available
Not Available


Not Available
Experimental Properties
Not Available

Drug created on October 20, 2016 21:43 / Updated on May 27, 2021 02:57