Bromelain is a pineapple enzyme which prevents the corona virus-2 from entering into ACE-2 receptor. Together with its anti-inflammatory and anticoagulant properties, bromelain may act as a potential therapeutic agent for COVID-19.
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Bromelain is a potential ACE-2 inhibitor for COVID-19
1. PINEAPPLE ENZYME:
BROMELAIN,
A POTENTIAL ACE-2
INHIBITOR FOR COVID-19
By
Kevin KF Ng, MD, PhD.
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, FL, USA
Email: kevinng68@gmail.com
A Slide Presentation for HealthCare Providers April 2022
2. Presentation Outline
▪ What is bromelain?
▪ Source of bromelain
▪ Absorption and distribution of bromelain
▪ Pharmacology of bromelain
▪ Clinical studies of bromelain
▪ Summary
3. What is bromelain?
▪ Bromelain is a protein digesting enzyme mixture called cysteine protease.
▪ It is derived from the stem, fruit and juice of a pineapple.
4. Bromelain content of extract from stem of pineapple
(Ananas comosus (L.) Merr) 2019
▪ Bromelain from pineapple stem has a
▪ molecular weight between 19-22 kDa.
▪ Bradford assay showed 0.476 µg/mL bromelain
concentration.
▪ Bromelain activity of Non freeze dried (NF) extract
showed 0.317 U/mL, while
▪ freeze dried (F) extract showed 0.212 stem U/mL.
https://aip.scitation.org/doi/10.1063/1.5061850
stem
6. Number of articles on “bromelain” in PubMed from
1946 to 2021
https://pubmed.ncbi.nlm.nih.gov/?term=+bromelain
7. Chemical structure of bromelain found in pineapple juice.
https://www.researchgate.net/figure/Chemical-structure-of-bromelain-found-in-pineapple-juice_fig1_298815490
Bromelain is a cysteine protease derived from the stem and fruit of the pineapple
8. Different types of protease in the bromelain mixture (Barrett et al., 2013).
https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/stem-bromelain
10. Pharmacokinetics of bromelain
▪ .
▪ Bromelain is absorbed into the human intestines and
remains biologically active in plasma.
▪ About 40% of labeled bromelain is absorbed from intestine
in high molecular form.
▪ The highest concentration of bromelain was identified
in the blood one hour after administration.
▪ About 50% of bromelain is bound to plasma protein.
▪ Half-life: of bromelain is 11.7±3.5 (8.5–19.9) hrs
https://en.wikipedia.org Int J Physiol Pathophysiol Pharmacol 2012;4(1):10-27
11. Absorption mechanisms of the gastrointestinal tract for
amino acids, peptides and protein molecules. (2012)
Int J Physiol Pathophysiol Pharmacol 2012;4(1):10-27
12. Radioactivity of I125-labeled bromelain in different organs of rats
6 hours after intra-duodenal application of 7.6 mg bromelain (2012)
Int J Physiol Pathophysiol Pharmacol 2012;4(1):10-27
●
13. Bromelain’s penetration into the blood and sinonasal mucosa
in patients with chronic rhinosinusitis (2018)
▪ The aim of this research is to investigate penetration of Bromelain into sinonasal
mucosa in patients with chronic rhinosinusitis (CRS) versus a control group.
▪ Bromelain is derived from pineapple (Ananas comosus) and has various
pharmacological effects. 40 patients (20 patients and 20 controls) were enrolled in
the study. Bromelain 500 mg tablet twice daily was administered for 30 days.
▪ We scored bromelain presence in turbinate and ethmoid mucosas and in the serum
of both the groups.
▪ Bromelain has an excellent distribution from blood to rhinosinusal mucosa. Its
diffusion ability may allow the use of bromelain as an anti-inflammatory agent in
paranasal sinus pathologies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036946/
16. Bromelain Inhibits entry of SARS-CoV-2 into VeroE6 Cells
via ACE-2 and TMPRSS2 (2020)
https://www.biorxiv.org/content/10.1101/2020.09.16.297366v1.full
17. Bromelain inhibits the release of
inflammatory mediators (2020)
https://www.medrxiv.org/content/10.1101/2020.12.22.20245993v1.full
Mediators
18. Bromelain prevents formation of cytokine storm in COVID-19 (2020)
Adapted from https://www.biorxiv.org/content/10.1101/2020.09.16.297366v1.full
20. Effects of different bromelain doses on serum fibrinogen and
prothrombin time 10 minutes after iv. injection (1990)
Planta Med. 56 (1990) 251
21. Increase of serum fibrinolytic activity of bromelain treated animals
in comparison to an untreated control group with
different doses of bromelain (1990)
Planta Med. 56 (1990) 251
24. Clinical applications of Bromelain as anti-inflammatory agent (2016)
https://www.researchgate.net/publication/301923082_Bromelain_Methods_of_Extraction_Purification_and_Therapeutic_Applications
25. Clinical applications of Bromelain as anticancer agent (2016)
https://www.researchgate.net/publication/301923082_Bromelain_Methods_of_Extraction_Purification_and_Therapeutic_Applications
26. Clinical application of Bromelain on
gastrointestinal disorders (2016)
https://www.researchgate.net/publication/301923082_Bromelain_Methods_of_Extraction_Purification_and_Therapeutic_Applications
27. Clinical application of of Bromelain on
thrombosis and skin disorders(2016)
https://www.researchgate.net/publication/301923082_Bromelain_Methods_of_Extraction_Purification_and_Therapeutic_Applications
28. Review of clinical applications of bromelain
▪ No clinical study on the use of bromelain on COVID-19 had been reported.
▪ The number of clinical studies for a specific condition is limited.
▪ The studies are not randomized and placebo controlled.
▪ The results are inconsistent.
▪ Thus, no conclusion can be made for the efficacy of bromelain.
29. Summary
▪ Bromelain is a cysteine protease derived from the
pineapple.
▪ It is mixture of at least five enzymes.
▪ Radio-labelled bromelain is absorbed in the intestine
▪ It is active in plasma with half-life of 11.7±3.5 (8.5–19.9) hrs
▪ Its anti-SARS-CoV-2 and anti-inflammatory properties have
been demonstrated in vitro.
▪ No clinical study of using bromelain in COVID-19 has been
reported.