The efficacy of propolis extracts as a food supplement in patients with COVID-19

Year 2023, Volume: 40 Issue: 3, 443 - 447, 30.09.2023

Betül Değer Kulaksız , Orhan Değer , Ali Timuçin Atayoğlu , Ergün Sevil , Deniz Kulaksız

Abstract

Propolis is a natural immunomodulator with anticancer, antiviral, and anti-inflammatory effects. Propolis may be considered an agent in the supportive treatment of COVID-19. Propolis is known for its wide range of pharmacological properties, with many studies finding it effective in both the prevention and treatment of a variety of conditions. Forty-five patients who were hospitalized in our hospital and did not need intensive care were divided into groups of 15. The patients were receiving the standard COVID-19 treatment protocol. In the randomized, controlled study, one group of patients received 2 ml of water extract of propolis (WEP) (50 mg/ml) orally three times a day for one week, while another group received 1 ml of olive oily extract of propolis (64 mg/ml) plus 1 ml of olive oily Perga extract (120 mg/ml) (OEP). Hospital discharge times and changes in biochemical parameters were used as indicators of recovery. The WEP and OEP groups were found to have statistically significantly better D-dimer, CRP, and WBC results than the control group when the improvement in parameters between the groups were compared. Significantly different hospital discharge times in groups 1 and 2 were found compared to the control group. The addition of propolis to the treatment as a food supplement has a positive effect on the recovery of patients with COVID-19 and may shorten the treatment time. The use of propolis as a food supplement has been shown to have a range of health benefits, and the addition of it to the treatment regimen for COVID-19 may help to reduce the severity and duration of symptoms.

Keywords

caffeic acid, coronavirus, COVID-19, propolis

References

• 1. Rello J, Belliato M, Dimopoulos MA, Giamarellos-Bourboulis EJ, Jaksic V, Martin-Loeches I, et al. Update in COVID-19 in the intensive care unit from the 2020 HELLENIC Athens International symposium. Anaesth Crit Care Pain Med. 2020 Dec;39(6):723–30.
• 2. Docea A, Tsatsakis A, Albulescu D, Cristea O, Zlatian O, Vinceti M, et al. A new threat from an old enemy: Re emergence of coronavirus (Review). Int J Mol Med. 2020 Mar 27.
• 3. Coronaviridae Study Group. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020 Apr 2;5(4):536–44.
• 4. D’Souza R, Ashraf R, Rowe H, Zipursky J, Clarfield L, Maxwell C, et al. Pregnancy and <scp>COVID</scp> ‐19: pharmacologic considerations. Ultrasound in Obstetrics & Gynecology. 2021 Feb;57(2):195–203.
• 5. To KKW, Tsang OTY, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 May;20(5):565–74.
• 6. Rijkers G, Murk JL, Wintermans B, van Looy B, van den Berge M, Veenemans J, et al. Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections. J Infect Dis. 2020 Sep 14;222(8):1265–9.
• 7. Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID‐19. Journal of Thrombosis and Haemostasis. 2020 May 27;18(5):1023–6.
• 8. Rinott E, Kozer E, Shapira Y, Bar-Haim A, Youngster I. Ibuprofen use and clinical outcomes in COVID-19 patients. Clinical Microbiology and Infection. 2020 Sep;26(9):1259.e5-1259.e7.
• 9. Wong AY, MacKenna B, Morton CE, Schultze A, Walker AJ, Bhaskaran K, et al. Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts. Ann Rheum Dis. 2021 Jul;80(7):943–51.
• 10. Sterne JAC, Murthy S, Diaz J V., Slutsky AS, Villar J, Angus DC, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19. JAMA. 2020 Oct 6;324(13):1330.
• 11. Kmietowicz Z. Covid-19: Selected NHS patients will be treated with remdesivir. BMJ. 2020 May 26;m2097.
• 12. Marconi VC, Ramanan A V, de Bono S, Kartman CE, Krishnan V, Liao R, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Sep.
• 13. Abbaspour Kasgari H, Moradi S, Shabani AM, Babamahmoodi F, Davoudi Badabi AR, Davoudi L, et al. Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial. Journal of Antimicrobial Chemotherapy. 2020 Nov 1;75(11):3373–8.
• 14. Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, et al. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19. JAMA. 2020 Dec 8;324(22):2292.
• 15. Freedberg DE, Conigliaro J, Wang TC, Tracey KJ, Callahan M V., Abrams JA, et al. Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study. Gastroenterology. 2020 Sep;159(3):1129-1131.e3.
• 16. Mather JF, Seip RL, McKay RG. Impact of Famotidine Use on Clinical Outcomes of Hospitalized Patients With COVID-19. American Journal of Gastroenterology. 2020 Oct;115(10):1617–23.
• 17. Balandrin MF, Klocke JA, Wurtele ES, Bollinger WmH. Natural Plant Chemicals: Sources of Industrial and Medicinal Materials. Science (1979). 1985 Jun 7;228(4704):1154–60.
• 18. Mani JS, Johnson JB, Steel JC, Broszczak DA, Neilsen PM, Walsh KB, et al. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020 Jul;284:197989.
• 19. Turcatto AP, Lourenço AP, De Jong D. Propolis consumption ramps up the immune response in honey bees infected with bacteria. Apidologie. 2018;49(3):287–96. 20. Berretta AA, Nascimento AP, Bueno PCP, de Oliveira Lima Leite Vaz MM, Marchetti JM. Propolis Standardized Extract (EPP-AF®), an Innovative Chemically and Biologically Reproducible Pharmaceutical Compound for Treating Wounds. Int J Biol Sci. 2012;8(4):512–21.
• 21. Miguel MG, Nunes S, Dandlen SA, Cavaco AM, Antunes MD. Phenols, flavonoids and antioxidant activity of aqueous and methanolic extracts of propolis (Apis mellifera L.) from Algarve, South Portugal. Food Science and Technology. 2014;34(1):16–23.
• 22. Xie Y, Huang B, Yu K, Shi F, Liu T, Xu W. Caffeic acid derivatives: A new type of influenza neuraminidase inhibitors. Bioorg Med Chem Lett. 2013;23(12):3556–60.
• 23. Utsunomiya H, Ichinose M, Ikeda K, Uozaki M, Morishita J, Kuwahara T, et al. Inhibition by caffeic acid of the influenza a virus multiplication in vitro. Int J Mol Med. 2014;34(4):1020–4.
• 24. Wang GF, Shi LP, Ren YD, Liu QF, Liu HF, Zhang RJ, et al. Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo and in vitro. Antiviral Res. 2009;83(2):186–90.
• 25. Cheng Z, Sun G, Guo W, Huang Y, Sun W, Zhao F, et al. Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines. Virol Sin. 2015;30(4):261–8.
• 26. Shi ZH, Li NG, Tang YP, Wei-Li, Lian-Yin, Yang JP, et al. Metabolism-based synthesis, biologic evaluation and SARs analysis of O-methylated analogs of quercetin as thrombin inhibitors. Eur J Med Chem. 2012 Aug;54:210–22.
• 27. Tsai FJ, Lin CW, Lai CC, Lan YC, Lai CH, Hung CH, et al. Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins. Food Chem. 2011 Sep;128(2):312–22.
• 28. Okamoto Y, Tanaka M, Fukui T, Masuzawa T. Brazilian propolis inhibits the differentiation of Th17 cells by inhibition of interleukin-6-induced phosphorylation of signal transducer and activator of transcription 3. Immunopharmacol Immunotoxicol. 2012;34(5):803–9.
• 29. Szliszka E, Kucharska AZ, Sokół-Łętowska A, Mertas A, Czuba ZP, Król W. Chemical Composition and Anti-Inflammatory Effect of Ethanolic Extract of Brazilian Green Propolis on Activated J774A.1 Macrophages. Evidence-Based Complementary and Alternative Medicine. 2013;2013:1–13.
• 30. Lin CW, Tsai FJ, Tsai CH, Lai CC, Wan L, Ho TY, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res. 2005 Oct;68(1):36–42.
• 31. Maruta H, He H. PAK1-blockers: Potential Therapeutics against COVID-19. Med Drug Discov. 2020 Jun;6:100039. 32. Da J, Xu M, Wang Y, Li W, Lu M, Wang Z. Kaempferol Promotes Apoptosis While Inhibiting Cell Proliferation via Androgen-Dependent Pathway and Suppressing Vasculogenic Mimicry and Invasion in Prostate Cancer. Analytical Cellular Pathology. 2019 Dec 1;2019:1–10.
• 33. Sekiou O, Bouziane I, Bouslama Z, Djemel A. In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine against. ChemRxiv. 2020;2.
• 34. Schwarz S, Sauter D, Wang K, Zhang R, Sun B, Karioti A, et al. Kaempferol Derivatives as Antiviral Drugs against the 3a Channel Protein of Coronavirus. Planta Med. 2014 Jan 23;80(02/03):177–82.
• 35. Yoon SH, Lee KH, Kim JY, Lee YK. Pneumonia in Korea. Korean J Radiol. 2020;21(4):494–500.
• 36. Sahin A, Turkmen S, Guzel N, Mentese A, Turedi S, Karahan SC, et al. A Comparison of the Effects of Grayanotoxin-Containing Honey (Mad Honey), Normal Honey, and Propolis on Fracture Healing. Medical Principles and Practice. 2018;27(2):99–106.
• 37. Silveira MAD, Teles F, Berretta AA, Sanches TR, Rodrigues CE, Seguro AC, et al. Effects of Brazilian green propolis on proteinuria and renal function in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled trial. BMC Nephrol. 2019 Dec 25;20(1):140.
• 38. Silveira MAD, De Jong D, Berretta AA, Galvão EB dos S, Ribeiro JC, Cerqueira-Silva T, et al. Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial. Biomedicine & Pharmacotherapy. 2021 Jun;138:111526.
• 39. Gallo Marin B, Aghagoli G, Lavine K, Yang L, Siff EJ, Chiang SS, et al. Predictors of <scp>COVID</scp> ‐19 severity: A literature review. Rev Med Virol. 2021 Jan 30;31(1):1–10.
• 40. Jain V, Yuan JM. Predictive symptoms and comorbidities for severe COVID-19 and intensive care unit admission: a systematic review and meta-analysis. Int J Public Health. 2020 Jun 25;65(5):533–46.
• 41. Osés SM, Marcos P, Azofra P, de Pablo A, Fernández-Muíño MÁ, Sancho MT. Phenolic Profile, Antioxidant Capacities and Enzymatic Inhibitory Activities of Propolis from Different Geographical Areas: Needs for Analytical Harmonization. Antioxidants. 2020 Jan 15;9(1):75.
• 42. Bozkuş TN, Değer O, Yaşar A. Chemical characterization of water and ethanolic extracts of Turkish propolis by HPLC-DAD and GC-MS. J Liq Chromatogr Relat Technol. 2021 Jan 20;44(1–2):77–86.
• 43. Demir S, Aliyazicioglu Y, Turan I, Misir S, Mentese A, Yaman SO, et al. Antiproliferative and proapoptotic activity of Turkish propolis on human lung cancer cell line. Nutr Cancer. 2016 Jan 2;68(1):165–72.
• 44. Barlak Y, Değer O, Çolak M, Karataylı S, Bozdayı A, Yücesan F. Effect of Turkish propolis extracts on proteome of prostate cancer cell line. Proteome Sci. 2011;9(1):74.
• 45. de Barros MP, Sousa JPB, Bastos JK, de Andrade SF. Effect of Brazilian green propolis on experimental gastric ulcers in rats. J Ethnopharmacol. 2007 Apr;110(3):567–71.
• 46. Ali AM, Kunugi H. Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies. Molecules. 2021 Feb 25;26(5):1232.