Farzanegan, Behrooz

Jahangirifard, Alireza

Mirtajani, Seyed Bashir

Peyravian, Farzad

Sharifzadeh, Kurdistan

English

Journals Portal, Shahid Beheshti University of Medical Sciences

  Journal of Cellular & Molecular Anesthesia (JCMA)  Journal of Cellular & Molecular Anesthesia (JCMA) 284 Letter to the Editor    The Potential Role of Bromelain in the Treatment of SARS-COV-2  Kurdistan Sharifzadeh1, Behrooz Farzanegan2 , Seyed Bashir Mirtajani1  Farzad Peyravian3  , Alireza Jahangirifard3*   1 Lung transplant Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Tracheal Diseases Research Center, NRITLD, Shahid Beheshti University of Medical Sciences Tehran, Iran 3 Chronic Respiratory Disease Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran     Corresponding Author: Alireza Jahangirifard, MD, Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Dar Abad, Tehran, Iran.; Email: alirezajahangiri@sbmu.ac.ir; Phone number: (+98) 912 1820899  Please cite this article as: Sharifzadeh K, Farzanegan B, Mirtajani SB, Peyravian F, Jahangirifard A. The Potential Role of Bromelain in the Treatment of SARS-COV-2. J Cell Mol Anesth. 2020;5(4):284-5. https://doi.org/10.22037/jcma.v5i4.32113     Dear Editor The biggest challenge of last year worldwide has undoubtedly been to deal with the outbreak of the novel coronavirus (SARS -COV-2), which was spread from Wuhan, China to other parts of the world at the end of last year (2019).  SARS-COV-2 uses the ACE2 receptor to enter human cells and involve these receptors (1). ACE2 is capable of cleaving, des-Arg bradykinin which is involved locally in vessel dilation through binding to the B1 receptor (2). Des-Arg-BK is the only active metabolite of BK (3). It should be noted that activation of the B1 receptor in lung endothelial cells causes severe deterioration and increased mortality in many diseases; on the other hand, this receptor on endothelial cells is upregulated by proinflammatory cytokines (4). Followed local lung angioedema could chip into the disease by an increase of local immune cell influx and proinflammatory cytokines leading to increasing severity (5). This inflammation persuades more B1 expression, and possibly via antibody-dependent increase of viral infection leading to continued ACE2 dysfunction in the lung because of the durability of the virus (6). In this standpoint bradykinin-dependent, local lung angioedema via B1 and B2 receptors is a significant trait of SARS-COV-2 (7). Hence it seems that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. Bradykinin is a pro-inflammatory molecule (8). Bradykinin B1 and B2 receptors are constitutively expressed in the airways on several residential and/or immune cells (9). Their expression can also be induced by inflammatory mediators, usually associated with eosinophil and neutrophil recruitment, such as IL-4, IL-13, TNF-α, IL-6, and IL-8, via intracellular MAPK and NF-κB signaling (10). BK exerts its pharmacological effects, mainly vasodilation, by activating constitutively expressed B2 receptors (11). BK is metabolized by three metallopeptidases (5). Whereas, the angiotensin-converting enzyme (ACE) constitutes the main degradation pathway that transforms BK into its final inactive metabolite BK. Bromelain is an anti-inflammatory that plays a role in reducing serum and tissue levels of kininogen and bradykinin (12). This substance is obtained from raw pineapple extract and if orally administered, while retaining its properties, it is reabsorbed through the intestines (13). Numerous therapeutic properties of this substance are known for many diseases including bronchitis, sinusitis, arthritis, and inflammation. The positive effects on the mentioned diseases can be The Potential Role of Bromelain in the Treatment of SARS-COV-2                                                                    Sharifzadeh et al. Vol 5, No 4, Fall 2020 285 attributed to the anti-edema, anti-inflammatory, and coagulation-inhibiting properties of bromelain (14). 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 (13). As mentioned, bromelain has anti-inflammatory properties. On the other hand, this drug potentially activates the immune system in association with the rapid response to cellular stress (15). Conversely, bromelain reduces cytokine secretion when immune cells are already stimulated in the condition of inflammation-induced overproduction of cytokines. Thus, by carefully studying the pathogenesis and clinical signs of patients with SARS -COV-2, the use of Bromelain can have a positive effect on the treatment process of these patients. However, to determine the type of treatment, the amount of administration, the duration of action of the drug and to determine the possible adverse effects, the implementation of a clinical process can play an effective role. Conflicts of Interest  The authors declare that there are no conflicts of interest.  References 1. Li G, He X, Zhang L, et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. Journal of autoimmunity. 2020:102463. 2. Marceau F. Kinin B1 receptors: a review. Immunopharmacology. 1995;30(1):1-26. 3. Decarie A, Adam A, Couture R. Effects of captopril and Icatibant on bradykinin (BK) and des [Arg9] BK in carrageenan-induced edema. Peptides. 1996;17(6):1009-15. 4. Qadri F, Bader M. Kinin B1 receptors as a therapeutic target for inflammation. Expert Opin Ther Targets. 2018;22(1):31-44. 5. Cyr M, Lepage Y, Blais C, Jr., Gervais N, Cugno M, Rouleau JL, et al. Bradykinin and des-Arg(9)-bradykinin metabolic pathways and kinetics of activation of human plasma. Am J Physiol Heart Circ Physiol. 2001;281(1):H275-83. 6. Smatti MK, Al Thani AA, Yassine HM. Viral-Induced Enhanced Disease Illness. Front Microbiol. 2018;9:2991. 7. Maurer M, Bader M, Bas M, Bossi F, Cicardi M, Cugno M, et al. New topics in bradykinin research. Allergy. 2011;66(11):1397-406. 8. Wang PH, Cenedeze MA, Campanholle G, Malheiros DM, Torres HA, Pesquero JB, et al. Deletion of bradykinin B1 receptor reduces renal fibrosis. Int Immunopharmacol. 2009;9(6):653-7. 9. Dutra RC, Bento AF, Leite DF, Manjavachi MN, Marcon R, Bicca MA, et al. The role of kinin B1 and B2 receptors in the persistent pain induced by experimental autoimmune encephalomyelitis (EAE) in mice: evidence for the involvement of astrocytes. Neurobiol Dis. 2013;54:82-93. 10. Ghahestani SM, Mahmoudi J, Hajebrahimi S, Sioofy-Khojine AB, Salehi-Pourmehr H, Sadeghi-Ghyassi F, et al. Bradykinin as a Probable Aspect in SARS-Cov-2 Scenarios: Is Bradykinin Sneaking out of Our Sight? Iran J Allergy Asthma Immunol. 2020;19(S1):13-7. 11. Prado GN, Taylor L, Zhou X, Ricupero D, Mierke DF, Polgar P. Mechanisms regulating the expression, self-maintenance, and signaling-function of the bradykinin B2 and B1 receptors. J Cell Physiol. 2002;193(3):275-86. 12. Secor ER, Jr., Carson WFt, Cloutier MM, Guernsey LA, Schramm CM, Wu CA, et al. Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease. Cell Immunol. 2005;237(1):68-75. 13. de Lencastre Novaes LC, Jozala AF, Lopes AM, de Carvalho Santos-Ebinuma V, Mazzola PG, Pessoa Junior A. Stability, purification, and applications of bromelain: A review. Biotechnol Prog. 2016;32(1):5-13. 14. Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evid Based Complement Alternat Med. 2004;1(3):251-7. 15. Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R. Potential role of bromelain in clinical and therapeutic applications. Biomed Rep. 2016;5(3):283-8.  

The Potential Role of Bromelain in the Treatment of SARS-COV-2

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The Potential Role of Bromelain in the Treatment of SARS-COV-2

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