The Effect of Bromelain (Anaheal) on Clinical and Para-Clinical Parameters in Hospitalized COVID-19 Patients
-
Alireza Jahangirifard
,
Ashkan Omidi
,
Kurdistan Sharifzadeh
,
Seysd Bashir Mirtajani
,
Farzad Peyravian
,
Saeid Safari
,
Maedeh Sadat Jafarzadeh
,
Seyed Hadi Mirhashemi
,
Behrooz Farzanegan
Abstract
The severity of COVID-19 disease and its mortality may be due to a localized vascular problem owing to the activation of bradykinin B1 receptors on endothelial cells in the lungs that occur following inflammation. Bromelain acts as an anti-inflammatory factor and can lower the level of bradykinin in the serum and tissues. Patients with the novel coronavirus (COVID-19) referred to Masih Daneshvari Hospital in Tehran were included in the study after providing full explanations and obtaining written consent. The 40 patients with mild to moderate symptoms were randomly divided into the control group (No: 20) and sample (No: 20). In the sample group, a dose of 200 mg bromelain was given to patients every 8 hours. In the control group, placebo capsules were administered exactly at the above intervals. Clinical and paraclinical factors (including SaO2, RR body temperature, MAP, HR, CRP, ESR, AST, ALT, Bil, BUN, Cr, WBC, Lymph, LDH, Plt were evaluated on a regular basis for up to five days. The results were evaluated using t-test and SPSS21 software. After treatment, the sample (Bromelain) group indicated significant improvement in SaO2, RR, HR, AST, ALT, BUN, ESR, LDH, and WBC and Lymphocyte count (P<0.05). Other factors did not have a significant difference with the control group. Bromelain causes improvement in some clinical symptoms such as respiratory parameters and para clinical items of mild to moderate hospitalized COVID-19 patients, so it can be a promising treatment. Furthered evaluation of larger groups is recommended.
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4- Manolis AS, Manolis TA, Manolis AA, Melita H. The Controversy of Renin–Angiotensin-System Blocker Facilitation Versus Countering COVID-19 Infection. Journal of cardiovascular pharmacology. 2020 Oct 1;76(4):397-406.
5- Polycarpou A, Howard M, Farrar CA, Greenlaw R, Fanelli G, Wallis R, Klavinskis LS, Sacks S. Rationale for targeting complement in COVID‐19. EMBO molecular medicine. 2020 Aug 7;12(8):e12642.
6- Sharifzadeh K, Farzanegan B, Mirtajani SB, Peyravian F, Jahangirifard A. The Potential Role of Bromelain in the Treatment of SARS-COV-2. Journal of Cellular & Molecular Anesthesia. 2018;5(4):284-5.
7- Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, Scarlata S, Agrò FE. COVID‐19 diagnosis and management: a comprehensive review. Journal of Internal Medicine. 2020 Apr 29.
8- Ricciardolo FL, Folkerts G, Folino A, Mognetti B. Bradykinin in asthma: Modulation of airway inflammation and remodelling. European journal of pharmacology. 2018 May 15;827:181-8.
9- Dutra RC, Bento AF, Leite DF, Manjavachi MN, Marcon R, Bicca MA, Pesquero JB, Calixto JB. 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. Neurobiology of disease. 2013 Jun 1;54:82-93.
10- Vo TS, Ngo DH, Kim SK. Potential targets for anti-inflammatory and anti-allergic activities of marine algae: An overview. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy). 2012 Apr 1;11(2):90-101.
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. Journal of cellular physiology. 2002 Dec;193(3):275-86.
12- Prins M, Schellens CJ, Van Leeuwen MW, Rothuizen J, Teske E. Coagulation disorders in dogs with hepatic disease. The Veterinary Journal. 2010 Aug 1;185(2):163-8.
13- Zhai Z, Li C, Chen Y, Gerotziafas G, Zhang Z, Wan J, Liu P, Elalamy I, Wang C. Prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus statement before guidelines. Thrombosis and haemostasis. 2020 Jun;120(6):937.
14- Seligman B. Bromelain: an anti-inflammatory agent. Angiology. 1962 Nov;13(11):508-10.
15- Hale LP, Greer PK, Trinh CT, James CL. Proteinase activity and stability of natural bromelain preparations. International immunopharmacology. 2005 Apr 1;5(4):783-93.
16- Moghadam MY, Nemat-Shahi M, Dowlat-Abadi B, Safari SE, Yajan S. Association Between Bispectral Index (BIS) Value and Postoperative Shivering in Patients Undergoing Orthopedic Surgery. Open access Macedonian journal of medical sciences. 2019 Apr 15;7(7):1166.
17- Engwerda CR, Andrew D, Ladhams A, Mynott TL. Bromelain modulates T cell and B cell immune responses in vitro and in vivo. Cellular immunology. 2001 May 25;210(1):66-75.
18- Salas CE, Gomes MT, Hernandez M, Lopes MT. Plant cysteine proteinases: evaluation of the pharmacological activity. Phytochemistry. 2008 Sep 1;69(12):2263-9.
19- Metzig CA, Grabowska ED, Eckert KL, Rehse KL, Maurer HR. Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo. in vivo. 1999 Jan 1;13(1):7-12.
20- Huang JR, Wu CC, Hou RC, Jeng KC. Bromelain inhibits lipopolysaccharide-induced cytokine production in human THP-1 monocytes via the removal of CD14. Immunological investigations. 2008 Jan 1;37(4):263-77.
21- Ahmed AK, Albalawi YS, Shora HA, Abdelseed HK, Al-Kattan AN. Effects of quadruple therapy: zinc, quercetin, bromelain and vitamin C on the clinical outcomes of patients infected with COVID-19. Rea Int J of End and Diabe. 2020;1(1):018-21.
22- Secor Jr ER, Carson IV WF, Cloutier MM, Guernsey LA, Schramm CM, Wu CA, Thrall RS. Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease. Cellular immunology. 2005 Sep 1;237(1):68-75.
23- Secor Jr ER, Shah SJ, Guernsey LA, Schramm CM. Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma. Alternative therapies in health and medicine. 2012 Sep 1;18(5):9.
24- Secor ER, Carson WF, Singh A, Pensa M, Guernsey LA, Schramm CM, Thrall RS. Oral bromelain attenuates inflammation in an ovalbumin-induced murine model of asthma. Evidence-Based Complementary and Alternative Medicine. 2008 Mar 1;5.
25- Sagar S, Rathinavel AK, Lutz WE, Struble LR, Khurana S, Schnaubelt AT, Mishra NK, Guda C, Broadhurst MJ, Reid SP, Bayles KW. Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells. Biorxiv. 2020 Jan 1.
26- Al-Otaibi WR, Virk P, Elobeid M. Ameliorative potential of stem bromelain on lead-induced toxicity in Wistar rats. Acta Biologica Hungarica. 2015 Jun;66(2):149-60.
27- Nguyen DH, Lee SI, Cheong JY, Kim IH. Influence of low-protein diets and protease and bromelain supplementation on growth performance, nutrient digestibility, blood urine nitrogen, creatinine, and faecal noxious gas in growing–finishing pigs. Canadian Journal of Animal Science. 2018 Mar 9;98(3):488-97.
28- Hossain MM, Lee SI, Kim IH. Effects of bromelain supplementation on growth performance, nutrient digestibility, blood profiles, faecal microbial shedding, faecal score and faecal noxious gas emission in weanling pigs. Veterinarni Medicina. 2015 Oct 1;60(10).
29- Hu PA, Chen CH, Guo BC, Kou YR, Lee TS. Bromelain Confers Protection against the Non-Alcoholic Fatty Liver Disease in Male C57bl/6 Mice. Nutrients. 2020 May;12(5):1458.
2- Lau H, Khosrawipour V, Kocbach P, Mikolajczyk A, Schubert J, Bania J, Khosrawipour T. The positive impact of lockdown in Wuhan on containing the COVID-19 outbreak in China. Journal of travel medicine. 2020 Apr;27(3): taaa037.
3- Marjani M, Tabarsi P, Moniri A, Hashemian SM, Nadji SA, Abtahian Z, Malekmohammad M, Kiani A, Farzanegan B, Eslaminejad A, Fakharian A. NRITLD Protocol for the Management of Patients with COVID-19 Admitted to Hospitals. Tanaffos. 2020 Nov;19(2):91.
4- Manolis AS, Manolis TA, Manolis AA, Melita H. The Controversy of Renin–Angiotensin-System Blocker Facilitation Versus Countering COVID-19 Infection. Journal of cardiovascular pharmacology. 2020 Oct 1;76(4):397-406.
5- Polycarpou A, Howard M, Farrar CA, Greenlaw R, Fanelli G, Wallis R, Klavinskis LS, Sacks S. Rationale for targeting complement in COVID‐19. EMBO molecular medicine. 2020 Aug 7;12(8):e12642.
6- Sharifzadeh K, Farzanegan B, Mirtajani SB, Peyravian F, Jahangirifard A. The Potential Role of Bromelain in the Treatment of SARS-COV-2. Journal of Cellular & Molecular Anesthesia. 2018;5(4):284-5.
7- Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, Scarlata S, Agrò FE. COVID‐19 diagnosis and management: a comprehensive review. Journal of Internal Medicine. 2020 Apr 29.
8- Ricciardolo FL, Folkerts G, Folino A, Mognetti B. Bradykinin in asthma: Modulation of airway inflammation and remodelling. European journal of pharmacology. 2018 May 15;827:181-8.
9- Dutra RC, Bento AF, Leite DF, Manjavachi MN, Marcon R, Bicca MA, Pesquero JB, Calixto JB. 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. Neurobiology of disease. 2013 Jun 1;54:82-93.
10- Vo TS, Ngo DH, Kim SK. Potential targets for anti-inflammatory and anti-allergic activities of marine algae: An overview. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy). 2012 Apr 1;11(2):90-101.
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. Journal of cellular physiology. 2002 Dec;193(3):275-86.
12- Prins M, Schellens CJ, Van Leeuwen MW, Rothuizen J, Teske E. Coagulation disorders in dogs with hepatic disease. The Veterinary Journal. 2010 Aug 1;185(2):163-8.
13- Zhai Z, Li C, Chen Y, Gerotziafas G, Zhang Z, Wan J, Liu P, Elalamy I, Wang C. Prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus statement before guidelines. Thrombosis and haemostasis. 2020 Jun;120(6):937.
14- Seligman B. Bromelain: an anti-inflammatory agent. Angiology. 1962 Nov;13(11):508-10.
15- Hale LP, Greer PK, Trinh CT, James CL. Proteinase activity and stability of natural bromelain preparations. International immunopharmacology. 2005 Apr 1;5(4):783-93.
16- Moghadam MY, Nemat-Shahi M, Dowlat-Abadi B, Safari SE, Yajan S. Association Between Bispectral Index (BIS) Value and Postoperative Shivering in Patients Undergoing Orthopedic Surgery. Open access Macedonian journal of medical sciences. 2019 Apr 15;7(7):1166.
17- Engwerda CR, Andrew D, Ladhams A, Mynott TL. Bromelain modulates T cell and B cell immune responses in vitro and in vivo. Cellular immunology. 2001 May 25;210(1):66-75.
18- Salas CE, Gomes MT, Hernandez M, Lopes MT. Plant cysteine proteinases: evaluation of the pharmacological activity. Phytochemistry. 2008 Sep 1;69(12):2263-9.
19- Metzig CA, Grabowska ED, Eckert KL, Rehse KL, Maurer HR. Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo. in vivo. 1999 Jan 1;13(1):7-12.
20- Huang JR, Wu CC, Hou RC, Jeng KC. Bromelain inhibits lipopolysaccharide-induced cytokine production in human THP-1 monocytes via the removal of CD14. Immunological investigations. 2008 Jan 1;37(4):263-77.
21- Ahmed AK, Albalawi YS, Shora HA, Abdelseed HK, Al-Kattan AN. Effects of quadruple therapy: zinc, quercetin, bromelain and vitamin C on the clinical outcomes of patients infected with COVID-19. Rea Int J of End and Diabe. 2020;1(1):018-21.
22- Secor Jr ER, Carson IV WF, Cloutier MM, Guernsey LA, Schramm CM, Wu CA, Thrall RS. Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease. Cellular immunology. 2005 Sep 1;237(1):68-75.
23- Secor Jr ER, Shah SJ, Guernsey LA, Schramm CM. Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma. Alternative therapies in health and medicine. 2012 Sep 1;18(5):9.
24- Secor ER, Carson WF, Singh A, Pensa M, Guernsey LA, Schramm CM, Thrall RS. Oral bromelain attenuates inflammation in an ovalbumin-induced murine model of asthma. Evidence-Based Complementary and Alternative Medicine. 2008 Mar 1;5.
25- Sagar S, Rathinavel AK, Lutz WE, Struble LR, Khurana S, Schnaubelt AT, Mishra NK, Guda C, Broadhurst MJ, Reid SP, Bayles KW. Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells. Biorxiv. 2020 Jan 1.
26- Al-Otaibi WR, Virk P, Elobeid M. Ameliorative potential of stem bromelain on lead-induced toxicity in Wistar rats. Acta Biologica Hungarica. 2015 Jun;66(2):149-60.
27- Nguyen DH, Lee SI, Cheong JY, Kim IH. Influence of low-protein diets and protease and bromelain supplementation on growth performance, nutrient digestibility, blood urine nitrogen, creatinine, and faecal noxious gas in growing–finishing pigs. Canadian Journal of Animal Science. 2018 Mar 9;98(3):488-97.
28- Hossain MM, Lee SI, Kim IH. Effects of bromelain supplementation on growth performance, nutrient digestibility, blood profiles, faecal microbial shedding, faecal score and faecal noxious gas emission in weanling pigs. Veterinarni Medicina. 2015 Oct 1;60(10).
29- Hu PA, Chen CH, Guo BC, Kou YR, Lee TS. Bromelain Confers Protection against the Non-Alcoholic Fatty Liver Disease in Male C57bl/6 Mice. Nutrients. 2020 May;12(5):1458.
| Files | ||
| Issue | Vol 59, No 12 (2021) | |
| Section | Articles | |
| DOI | https://doi.org/10.18502/acta.v59i12.8066 | |
| Keywords | ||
| Bromelain Coronavirus disease 2019 (COVID-19) Inflammatory response Clinical symptoms Respiratory parameters Immunological factors | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Jahangirifard A, Omidi A, Sharifzadeh K, Mirtajani SB, Peyravian F, Safari S, Jafarzadeh MS, Mirhashemi SH, Farzanegan B. The Effect of Bromelain (Anaheal) on Clinical and Para-Clinical Parameters in Hospitalized COVID-19 Patients. Acta Med Iran. 2021;59(12):726-732.
