Eucalyptus oil as adjuvant therapy for coronavirus disease 19 (covid-19): a randomized clinical trial

Arif Santoso; Rasiha; Muthiah Nur Afifah; Munawir Muhammad; Andi Rofian Sultan; Muhammad Rezky Juni; Priady Wira Prasetia; Andreza; Idrianti Idrus; Andi Munawirah; Yuyun Widaningsih; Firdaus Hamid; Idrus A. Paturusi; M. Nasrum Massi; Asrul Abdul Azis; Niluh Putu Indi Dharmayanti; Harimurti Nuradji; Diana Nurjanah; Fadjry  Djufry; Evie Safitri

doi:10.15562/bmj.v12i3.4388

Eucalyptus oil as adjuvant therapy for coronavirus disease 19 (covid-19): a randomized clinical trial

Arif Santoso ,

Rasiha ,

Muthiah Nur Afifah ,

Munawir Muhammad ,

Andi Rofian Sultan ,

Muhammad Rezky Juni ,

Priady Wira Prasetia ,

Andreza ,

Idrianti Idrus ,

Andi Munawirah ,

Yuyun Widaningsih ,

Firdaus Hamid ,

Idrus A. Paturusi ,

M. Nasrum Massi ,

Asrul Abdul Azis ,

Niluh Putu Indi Dharmayanti ,

Harimurti Nuradji ,

Diana Nurjanah ,

Fadjry Djufry ,

Evie Safitri ,

pdf |
DOI: https://doi.org/10.15562/bmj.v12i3.4388 |
Published: 2023-08-22

Abstract

Link of Video Abstract: https://youtu.be/WzYiDQR2RvA

Introduction: The coronavirus disease 19 (COVID-19) vaccination scheme is still being implemented worldwide, but problems with stock availability and other factors are still impeding this endeavor, especially in developing nations like Indonesia. Ethnopharmacology is known to provide a good source of a cheap candidate for anti-inflammation drugs. This study was conducted to determine the effectiveness of affordable adjuvant therapy, Eucalyptus oil, which has been used as a household remedy for respiratory tract infections in Indonesia.

Methods: 52 mild-moderate COVID-19 patients were randomly assigned for a prospective clinical trial. A group of 26 patients was given standard COVID-19 treatment as a control group, while another 26 patients as the treated group were given standard therapy and use Eucalyptus oil as an adjuvant. The clinical sign and symptoms, cytokines interleukin (IL) 6, IL-10, and transforming growth factor-beta (TGF-β) profiles were recorded during the study period.

Result: There was a trend of better improvement of clinical symptoms among patients who received adjuvant treatment than the control group. Altered smell (p = 0.003) and cough (p = 0.641) recovered faster in the treated group. While there was no marked difference in IL-10 and TGF-β levels among both groups, IL-6 level in the treated group was significantly lower and the neutrophil-to-lymphocyte ratio (NLR) was significantly decreased (p < .05) than the control.

Conclusion: Using Eucalyptus oil as an adjuvant of COVID-19 treatment promotes faster recovery of mild-moderate COVID-19 patients, probably via inhibition of the IL-6-mediated inflammation process.

References

Setiyowati E, Anggraeni R, Winoto PM, da Silva Soares Pereira D, Lopes P, Martins AT. Acceptance of the covid-19 vaccine based on health belief model. Bali Med J. 2022;11(3):1319–24. DOI: hhttp://dx.doi.org/10.15562/bmj.v11i3.3549.
Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: A meta-analysis. J Med Virol. 2020;92(11):2283–5. DOI: https://doi.org/10.1002/jmv.25948.
Zhu J, Pang J, Ji P, Zhong Z, Li H, Li B, et al. Elevated interleukin-6 is associated with severity of COVID-19: A meta-analysis. J Med Virol. 2021;93(1):35–7. DOI: https://doi.org/10.1002/jmv.26085.
Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–8. DOI: https://doi.org/10.1007/s00134-020-05991-x
Rubbert-Roth A, Furst DE, Nebesky JM, Jin A, Berber E. A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases. Rheumatol Ther. 2018;5(1):21–42. DOI: https://doi.org/10.1007/s40744-018-0102-x
Pranata S, Vranada A, Armiyati Y, Samiasih A, Aisah S. Inflammatory markers for predicting severity , mortality , and need for intensive care treatments of a patient infected with covid-19 : a scoping review. 2023;12(1):324–30. DOI: https://doi.org/10.15562/bmj.v12i1.3751.
Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med. 2021;384(16):1503–16. DOI: https://doi.org/10.1056/nejmoa2028700.
Sandner G, Heckmann M, Weghuber J. Immunomodulatory activities of selected essential oils. Biomolecules. 2020;10(8):1–16. DOI: https://doi.org/10.3390/biom10081139.
Ho CL, Li LH, Weng YC, Hua KF, Ju TC. Eucalyptus essential oils inhibit the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through reducing MAPK and NF-κB pathways. BMC Complement Med Ther. 2020;20(1):200. DOI: https://doi.org/10.1186/s12906-020-02999-0.
Bastos VPD, Gomes AS, Lima FJB, Brito TS, Soares PMG, Pinho JPM, et al. Inhaled 1,8-cineole reduces inflammatory parameters in airways of ovalbumin-challenged guinea pigs. Basic Clin Pharmacol Toxicol. 2011;108(1):34–9. DOI: https://doi.org/10.1111/j.1742-7843.2010.00622.x.
Coelho-De-Souza LN, Leal-Cardoso JH, De Abreu Matos FJ, Lahlou S, Magalhães PJC. Relaxant effects of the essential oil of Eucalyptus tereticornis and its main constituent 1,8-cineole on guinea-pig tracheal smooth muscle. Planta Med. 2005;71(12):1173–5. DOI: https://doi.org/10.1055/s-2005-873173.
Juergens LJ, Worth H, Juergens UR. New perspectives for mucolytic, anti-inflammatory and adjunctive therapy with 1,8-Cineole in COPD and asthma: review on the new therapeutic approach. Adv Ther. 2020;37(5):1737–53. DOI: https://doi.org/10.1007/s12325-020-01279-0
Dev S, Kaur I. Bioactive molecules from eucalyptus essential oil as potential inhibitors of COVID 19 corona virus infection by molecular docking studies. Kragujev J Sci. 2020;(42):29–43.
Iqhrammullah M, Rizki DR, Purnama A, Duta TF, Harapan H, Idroes R, et al. Antiviral Molecular Targets of Essential Oils against SARS-CoV-2: A Systematic Review. Sci Pharm. 2023;91(1):15. DOI: https://doi.org/10.3390/scipharm91010015.
Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355–62. DOI: http://dx.doi.org/10.1038/s41577-020-0331-4
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet [Internet]. 2020;395(10224):565–74. DOI: http://dx.doi.org/10.1016/S0140-6736(20)30251-8
Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9. DOI: https://doi.org/10.1002/rmv.2141.
Barry CE, Nolan Y, Clarke RM, Lynch A, Lynch MA. Activation of c-Jun-N-terminal kinase is critical in mediating lipopolysaccharide-induced changes in the rat hippocampus. J Neurochem. 2005;93(1):221–31. DOI: https://doi.org/10.1111/j.1471-4159.2004.03011.x.
Sun Z, Arendt CW, Ellmeier W, Schaeffer EM, Sunshine MJ, Gandhl L, et al. PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes. Nature. 2000;404(6776):402–7. DOI: https://doi.org/10.1038/35006090.

[1] Setiyowati E, Anggraeni R, Winoto PM, da Silva Soares Pereira D, Lopes P, Martins AT. Acceptance of the covid-19 vaccine based on health belief model. Bali Med J. 2022;11(3):1319–24. DOI: hhttp://dx.doi.org/10.15562/bmj.v11i3.3549.

[2] Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: A meta-analysis. J Med Virol. 2020;92(11):2283–5. DOI: https://doi.org/10.1002/jmv.25948.

[3] Zhu J, Pang J, Ji P, Zhong Z, Li H, Li B, et al. Elevated interleukin-6 is associated with severity of COVID-19: A meta-analysis. J Med Virol. 2021;93(1):35–7. DOI: https://doi.org/10.1002/jmv.26085.

[4] Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–8. DOI: https://doi.org/10.1007/s00134-020-05991-x

[5] Rubbert-Roth A, Furst DE, Nebesky JM, Jin A, Berber E. A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases. Rheumatol Ther. 2018;5(1):21–42. DOI: https://doi.org/10.1007/s40744-018-0102-x

[6] Pranata S, Vranada A, Armiyati Y, Samiasih A, Aisah S. Inflammatory markers for predicting severity , mortality , and need for intensive care treatments of a patient infected with covid-19 : a scoping review. 2023;12(1):324–30. DOI: https://doi.org/10.15562/bmj.v12i1.3751.

[7] Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med. 2021;384(16):1503–16. DOI: https://doi.org/10.1056/nejmoa2028700.

[8] Sandner G, Heckmann M, Weghuber J. Immunomodulatory activities of selected essential oils. Biomolecules. 2020;10(8):1–16. DOI: https://doi.org/10.3390/biom10081139.

[9] Ho CL, Li LH, Weng YC, Hua KF, Ju TC. Eucalyptus essential oils inhibit the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through reducing MAPK and NF-κB pathways. BMC Complement Med Ther. 2020;20(1):200. DOI: https://doi.org/10.1186/s12906-020-02999-0.

[10] Bastos VPD, Gomes AS, Lima FJB, Brito TS, Soares PMG, Pinho JPM, et al. Inhaled 1,8-cineole reduces inflammatory parameters in airways of ovalbumin-challenged guinea pigs. Basic Clin Pharmacol Toxicol. 2011;108(1):34–9. DOI: https://doi.org/10.1111/j.1742-7843.2010.00622.x.

[11] Coelho-De-Souza LN, Leal-Cardoso JH, De Abreu Matos FJ, Lahlou S, Magalhães PJC. Relaxant effects of the essential oil of Eucalyptus tereticornis and its main constituent 1,8-cineole on guinea-pig tracheal smooth muscle. Planta Med. 2005;71(12):1173–5. DOI: https://doi.org/10.1055/s-2005-873173.

[12] Juergens LJ, Worth H, Juergens UR. New perspectives for mucolytic, anti-inflammatory and adjunctive therapy with 1,8-Cineole in COPD and asthma: review on the new therapeutic approach. Adv Ther. 2020;37(5):1737–53. DOI: https://doi.org/10.1007/s12325-020-01279-0

[13] Dev S, Kaur I. Bioactive molecules from eucalyptus essential oil as potential inhibitors of COVID 19 corona virus infection by molecular docking studies. Kragujev J Sci. 2020;(42):29–43.

[14] Iqhrammullah M, Rizki DR, Purnama A, Duta TF, Harapan H, Idroes R, et al. Antiviral Molecular Targets of Essential Oils against SARS-CoV-2: A Systematic Review. Sci Pharm. 2023;91(1):15. DOI: https://doi.org/10.3390/scipharm91010015.

[15] Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355–62. DOI: http://dx.doi.org/10.1038/s41577-020-0331-4

[16] Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet [Internet]. 2020;395(10224):565–74. DOI: http://dx.doi.org/10.1016/S0140-6736(20)30251-8

[17] Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9. DOI: https://doi.org/10.1002/rmv.2141.

[18] Barry CE, Nolan Y, Clarke RM, Lynch A, Lynch MA. Activation of c-Jun-N-terminal kinase is critical in mediating lipopolysaccharide-induced changes in the rat hippocampus. J Neurochem. 2005;93(1):221–31. DOI: https://doi.org/10.1111/j.1471-4159.2004.03011.x.

[19] Sun Z, Arendt CW, Ellmeier W, Schaeffer EM, Sunshine MJ, Gandhl L, et al. PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes. Nature. 2000;404(6776):402–7. DOI: https://doi.org/10.1038/35006090.

Eucalyptus oil as adjuvant therapy for coronavirus disease 19 (covid-19): a randomized clinical trial

Abstract

References

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