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Hatem Sameir Abbas et al. Universal Journal of Pharmaceutical Research 2020; 5(4):57-60
ISSN: 2456-8058 57 CODEN (USA): UJPRA3
Available online on 15.9.2020 at http://ujpr.org
Universal Journal of Pharmaceutical Research
An Intern ational Peer Reviewed Jo urnal
Open access to Pharmaceutical research
This is an open access article distributed under the terms of the Creative Commons
Attribution-Non Commercial Share Alike 4.0 License which permits unrestricted non
commercial use, provided the original work is properly cited
Volume 5, Issue 4, 2020
REVIEW ARTICLE
EUCALYPTUS ESSENTIAL OIL; AN OFF-LABEL USE TO PROTECT THE
WORLD FROM COVID-19 PANDEMIC: REVIEW-BASED HYPOTHESES
Hatem Sameir Abbass
Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University (Boys), Cairo 11371-Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Sinai University, Kantara 41636-Egypt.
ABSTRACT
Objective: Severe acute respiratory syndrome Coronavirus 2 causes both health and economic crises and up till now no drug or vaccine has yet
been approved. There is an increased demand to explore other complementary methods to protect the world. Eucalyptus essential oil; a popular off-
label drug used to relieve nasal congestion via inhalation with promising effects on the upper respiratory diseases including viral infections.
Methods: In order to provide review-based hypotheses demonstrating eucalyptus essential oil beneficial role; several published studies were
retrieved from different databases and websites till June 2020. The retrieved data declared the antiviral potentials against viruses of same subgenus
or with same pattern and the beneficial effects on respiratory system, immunity and overall health improvement, along with declaring the
application methods and safety.
Results: Off-label use of Eucalyptus essential oil by inhaling 12drops /150mL or 1.5% v/v solution boiling water may relief COVID-19 mild and
moderate symptoms as pain, cough, respiratory inflammation, cytokine storm and dyspnea.
Conclusions: Experimental and clinical data proved that inhalation of eucalyptus essential oil may provide the ability to reduce COVID -19
patients symptoms and morbidity risk factors and may play a role as a preventative technique complementary to WHO guidanc e for beating
COVID-19 virulence and transmission spread.
Keywords: Cineole, COVID-19, essential oil, eucalyptus oil, inhalation.
Article Info: Received 28 June 2020; Revised 20 July; Accepted 10 August, Available online 15 September 2020
Cite this article-
Abbass HS. Eucalyptus essential oil; an off-label use to protect the world from COVID-19 pandemic: review-
based hypotheses. Universal Journal of Pharmaceutical Research 2020; 5(4):57-60.
DOI: https://doi.org/10.22270/ujpr.v5i4.440
Address for Correspondence:
Dr. Hatem Sameir Abbass, Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University (Boys), Cairo 11371-
Egypt. Department of Pharmacognosy, Faculty of Pharmacy, Sinai University, Kantara 41636-Egypt., Tel: +00201092900910,
E-mail: hsam8406@azhar.edu.eg
INTRODUCTION
Corona virus disease 2019 (COVID-19) is a global
pandemic of Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2). It first appeared in
Wuhan, Hubei, China and then spreads all over the
world through respiratory droplets, contact and the
faecal-oral route1. World Health Organization (WHO)
listed COVID-19 as a public health emergency of
international concern due to its rapid and highly
infectious pattern. The last WHO situation report-134
up to date June 2, 2020 has confirmed a total number
of infected peoples to be 6194533 from which 376320
were died2. The nowadays pandemic is characterized
by intensity variation between countries, misleading
indication of case fatality rate and unclear data about
the virus and its virulence. The absence of vaccines and
treatments encouraged the control strategies role and
non-pharmacological measurements for communities3.
Several intervention therapeutic strategies were
reported as an alternative approach to control the
COVID-19 pandemic. From these strategies the
inhalation of Eucalyptus essential oil (EEO) which
reported in several publications in addition to folkloric
traditional use in some countries during the few last
days4-9. No clinical trial, in vivo or in vitro studies
demonstrate the EEO activity against COVID-19; but
several review-based expected potentials as antiviral,
co-infection control, symptoms relief or just a safe
hygienic lifestyle. Today many companies have
advertised to EEO as a product for prevention or
treatment of COVID-1910; but, US Food and Drug
Administration (FDA) had sent a warning letters to
such companies11. In this work I will declare both facts
and problems of EEO use in controlling COVID-19
pandemic.
METHODS
Literature search was performed using diffrent
databases as; Science Direct, Google Scholar, Web of
Science, PubMed, ClinicalTrials.gov and Scopus using
Hatem Sameir Abbas et al. Universal Journal of Pharmaceutical Research 2020; 5(4):57-60
ISSN: 2456-8058 58 CODEN (USA): UJPRA3
main key word “Eucalyptus” in addition to “COVID-
19, COPD, Antiviral, Anti-inflammatory, Immune
modulation, Antimicrobial, clinical trials, FDA,
Monograph, Inhalation and Potential”.
DISCUSSION
Off-label use of EEO: EEO widely used as Over The
Counter (OTC) drug in a single or combined form for
relieving nasal congestion via inhaling a few drops
either on a handkerchief or in a bowl of hot water12.
Vapor inhalation of EEO relief symptoms of
bronchitis, asthma, and chronic obstructive pulmonary
disease (COPD) which are the risk factors in COVID-
19 patients13. Traditional use of EEO for relief of
cough associated with cold are accepted without the
supervision of a medical practitioner via inhalation and
as a bath additive and had been described for a long
time14. 1,8-Cineole the major constituent of EEO (80-
95%) is well tolerated in inhalation administrations and
is registered as a licensed medicinal product which
available for airways inflammation for many years15.
As well Vicks VapoRub® vapors inhalation which
containing eucalyptus, camphor and menthol acting on
cold receptors in the nose are a common used off-label
drug. The German Standard zulassung, the
Pharmacopée Française and the WHO monograph
2002 had reported the use of EEO for the treatment of
respiratory tract disorders, bronchial catarrh and
stomach pain14. The Martindale reported that EEO
effective as an inhalant, often in combination with
other volatile oils for catarrh and coughs in a lot of
preparations16. EEO is approved by the FDA for food
use (EAFUS -Everything Added to Food in the United
States- list No 2081) [FDA 2013] and as OTC (Over
the counter) drug in cough/cold monograph sub-
categories nasal decongestant (mouthwash or lozenge),
antitussive and expectorant and in external analgesic
monograph sub-categories counter irritant, fever
blister/cold sore and poison ivy/oak/sumac and in skin
protectant monograph sub-categories astringent and
poison (ivy/oak/sumac)17.
COPD control by EEO: COPD is associated with
increased risk of morbidity in COVID-19 patients18.
Pretreatment with EEO markedly reduced the
production TNF-α and IL-β proinflammatory
cytokines, superoxide dismutase (SOD) activity and
malondialdehyde (MDA) level which indicates that
EEO might have its potential in COPD treatment19. The
anti-inflammatory effect EEO to reduce cytokine
release was confirmed also in ex-vivo cultured and
stimulated alveolar macrophages from patients with
(COPD)20. Few weeks (1-8) therapy with 1,8-Cineole
reduces exacerbations, dyspnea and specific airway
resistance in patients with COPD and improves lung
function parameters and health status by intervening in
the mucus membrane pathophysiology of airway
inflammation14.
Antiviral activity of EEO: The antiviral activity of
EEO was confirmed against an enveloped viruses
(similar to COVID-19); mumps virus obtained from
patients with respiratory tract infection21, herpes
simplex virus before or during host cell adsorption22,
H1N1 influenza virus23and inhibits avian influenza virus
H11N9 in aerosol, vapor and if being captured on a fiber
coating materials9. The inhibitory mechanism of EEO
is based on the inactivation of hemagglutinin protein of
the virus in its vapor phase9. As well, two preprint
articles by (Sharma et al.) demonstrated that eucalyptol
(1,8 cineole) and Jensenone from EEO represent
potential COVID-19 main viral proteinase (M-
pro/3CLpro) inhibitory effect by molecular docking
studies. Inhaling concentrated EEO vapors for 30
minutes followed by periodical inhaling vapor mixture
of EEO and tea tree oil (TTO) (50:50) with 30-120
minutes intervals; reduces the risk of infection with
SARS-CoV which is a highly pathogenic
coronavirus23,24.
Co-infection control activity of EEO: The
antibacterial potentials of EEO was confirmed by
activity against respiratory infecting bacteria;
Haemophilus influenzae, H. parainfluenzae,
Stenotrophomonas maltophilia and Streptococcus
pneumoniae21 and by inhalation prophylactic use
against colds, tuberculosis, flus and opportunistic
infections of the human respiratory system24. In
hospitals EEO used for controlling multidrug-resistant
bacteria25, reduce endotracheal tube biofilm microbial
contamination during ventilation process26 and showed
antifungal potential against intensive care units (ICU)
isolated yeast24,27. EEO fumes inhalation affords
bactericidal components killing infections in the nasal
passages, sinuses, bronchial tubes and lungs24.
Anti-inflammatory and Immune modulation
potentials of EEO: Dexamethasone today is the first
and only drug that has made a significant difference to
patient mortality for COVID-19 due to its anti-
inflammatory and immune modulation effects.
Surprisingly EEO can implement the innate cell-
mediated immune response and anti-inflammatory
properties28,29. COVID-19 hospitalized patients
developed at latter phase a syndrome known as
cytokine storm or hyperinflammatory syndrome due to
immune overactivation that increases the acute
respiratory distress and can lead to death30.
Pretreatment with EEO markedly reduced the
production of proinflammatory cytokines which
indicates that EEO might have its potential to stop
cytokine storm19. As well suppression of human lung
macrophages inflammatory responses by EEO and its
constituent 1,8-cineole was reported31.
Other activities of EEO: EEO decreasing patient’s
pain32, cough treatment33, aid in the recovery from
certain respiratory diseases24, air freshener, fumigating
agent34 and effective in cleaning mixtures for
degreasing, deodorizing and disinfection33,35.
Dose and safety of EEO: The WHO monograph EEO
reported doses were 12drops /150mL or 1.5% v/v
solution boiling water for inhalation three times
daily36,37. The oral LD50 in rats (2.5g/kg)38. A
toxicological study influenced the use of EEO with
certain concentration less than (233.44 mg/kg) to avoid
serious metabolic and cellular damage39. As well, EEO
also may cause irritation to the skin, toxic effects
especially in children and adverse effects as slurred
speech, ataxia, muscle weakness progressing to
unconsciousness and seizures if used in high
Hatem Sameir Abbas et al. Universal Journal of Pharmaceutical Research 2020; 5(4):57-60
ISSN: 2456-8058 59 CODEN (USA): UJPRA3
concentration40-42. Because of EEO strong odor, an
accidental poisoning is not common, as intoxication
occurs only via oral consumption of 4-5ml EEO5.
There is no danger of accumulating inhaled essential
oils in the body even with repeated inhalation as the
concentration of inhaled EOs decreases to half its
original value within 30-40 minutes24. However the oils
liquid phase are generally irritant and possibly toxic for
nasopharyngeal and lung epithelial cells, the vapor
phase of the same oils might be useful as inhalers for
respiratory infections in low concentrations15. Studies
on 1,8-cineole confirmed that it is well absorbed from
breathing air. Upon inhalation of 2 ml 1,8-cineole 99%
for 20 min. the blood serum concentration was
increasing in a linear way with distribution half-life 2-
13 min. and elimination half-life 31-281 min.
Clinical trials of EEO on human volunteers: The
effect of 0.25ml EEO inhalation for 10 minutes on
cardiovascular responses using a disposable face mask
was reported in (ClinicalTrials.gov Identifier:
NCT02656004) and smelling of pure EEO in vial for
training of the olfactory nerve for improving smell
sense after radiation therapy also reported in
(ClinicalTrials.gov Identifier: NCT03049358). EEO
100% concentration was confirmed as a safe method of
protection from mosquito bites on human volunteers
skin in indoor conditions34. Inhalation of EEO was
effective in reducing blood pressure and pain after total
knee replacement32. Another clinical study had
concluded that the treatment with 1,8-cineole of
patients with acute non-purulent rhinosinusitis was
effective and safe with only mild side effects and can
avoid antibiotic treatment43. Another study had
concluded that acute rhinosinusitis can be managed
by treatment with 1,8-cineole and confirmed its safety
and significant benefit for bronchitis44.
Precautions for using EEO: EEO should not be used
during pregnancy or lactation as there is no information
available on inhalation of EEO or its main constituent
1,8-cineole for pregnant women and 1,8-cineole has
been reported to penetrate the rodents placenta. EEO
should not be used for babies and very young children
less than 12 years as the risk of reflex spasm is
expected.
CONCLUSION
Off-label use of EEO as an inhaler via inhalation
vaporizers, diffusers or as a fragrance in cleaning
mixtures should be announced as a concomitant safe
hygienic lifestyle to hand washing, face mask wearing
and social distancing. The use of EEO for COVID-19
patients will reduce muscle and stomach pain, cough
and dyspnea which are the common symptoms, and
protect patients from co-infection susceptibility and
decrease chance of hyper inflammatory syndrome and
COPD associated risk morbidity. Researchers should
start the clinical trials and in vivo studies on EEO
safety and efficacy as soon as possible to confirm or
reject its antiviral potentials against COVID-19 to
evaluate the possibility of its use for treatment and/or
prevention. Community pharmacies and essential oil
manufactories should sell EEO just as an off-label drug
not as treatment or preventative protocol for COVID-
19 pandemic.
CONFLICT OF INTEREST
The author declares no conflict of interest.
REFERENCES
1. Yeo C, Kaushal S, Yeo D. Enteric involvement of corona
viruses: is faecal-oral transmission of SARS-CoV-2
possible? The lancet Gastroenterology & hepatology.
2020; 5(4):335-337.
https://doi.org/10.1016/S2468-1253(20)30048-0
2. Organization WH. Corona virus disease (COVID-19).
Situation Report 134. 2 June 2020.
3. Mansuri FM. Situation analysis and an insight into
assessment of pandemic COVID-19. J Taibah University
Medical Sci 2020; 15(2):85.
https://doi.org/10.1016/j.jtumed.2020.04.001
4. Marwah A, Marwah P. Coronavirus (COVID-19): A
protocol for prevention, treatment and control. J App Nat
Sci 2020:119-123.
https://doi.org/10.31018/jans.vi.2269
5. Nkeck JR, Tsafack EE, Ndoadoumgue AL, Endomba FT.
An alert on the incautious use of herbal medicines by sub-
Saharan African populations to fight against the COVID-
19. The Pan African Med J 2020; 35(26).
https://doi.org/10.11604/pamj.supp.2020.35.2.23161
6. Szalkai I, Radnai A, Karacsony F, Körmendi-Racz J,
Nyerges A, Hegyi G. Possibilities of pre-hospital
intervention in the prevention and treatment of COVID-19
recommendations of The Hungarian Integrative Medicine
Association. J Med Healthcare SRC/JMHC/118 J Med
Healthcare 2020; 2(2):2.
7. Ainane T. Moroccan traditional treatment for fever and
influenza, similar to symptoms of coronavirus COVID-19
disease: Mini Review. J Analyt Sci App Biotech
2020;2(1):1-3.
8. Chakraborty MK. Novel Corona Virus Disease 19 (N
COVID-19) Epidemic origin, symptoms and precaution
measure. Purakala 2020;31(8):1395-1409.
9. Panyod S, Ho C-T, Sheen L-Y. Dietary therapy and herbal
medicine for COVID-19 prevention: A review and
perspective. J Trad Comp Med 2020; 10(4):420-27.
https://doi.org/10.1016/j.jtcme.2020.05.004
10. Lim GY. Essential oils and COVID-19: Industry warns no
sufficient evidence for efficacy amid sales surge. 2020;
11. Ashley DD. Unapproved and Misbranded Products
Related to Corona virus Disease 2019 (COVID-19). 2020;
12. Shelley A, Horner K. Otolaryngology: Nasal perforation.
British Dent J 2017; 222(7):495-495.
https://doi.org/10.1038/sj.bdj.2017.288
13. Sadlon AE, Lamson DW. Immune-modifying and
antimicrobial effects of Eucalyptus oil and simple
inhalation devices. Alt Med Rev 2010; 15(1):33-43.
14. Assessment report on Eucalytus globulus Labill.,
Eucalyptus polybractea R.T. Baker and/or Eucalyptus
smithii R.T. Baker, aetheroleum.
15. Pasdaran A, Sheikhi D. Volatile oils: Potential agents for
the treatment of respiratory infections. The Microbiology
of Respiratory System Infections. Elsevier; 2016:237-261.
https://doi.org/10.1016/B978-0-12-804543-5.00016-6
16. Sweetman S. The complete drug reference (Martindale).
The Pharmaceutical Press, London; 2007.
17. FDA. OTC Active Ingredients.
18. Lippi G, Henry BM. Chronic obstructive pulmonary
disease is associated with severe corona virus disease 2019
(COVID-19). Respiratory Medicine. 2020; 167:105941.
https://doi.org/10.1016/j.rmed.2020.105941
19. Wang L, Sun J, Li W, Lv Y, Shi W, Zhao C. Protective
effect of eucalyptus oil against pulmonary destruction and
inflammation in COPD rats. J Dis Med Plts 2017; 3:17-22.
https://doi.org/10.11648/j.jdmp.20170301.14
Hatem Sameir Abbas et al. Universal Journal of Pharmaceutical Research 2020; 5(4):57-60
ISSN: 2456-8058 60 CODEN (USA): UJPRA3
20. Rantzsch U, Vacca G, Dück R, Gillissen A. Anti-
inflammatory effects of Myrtol standardized and other
essential oils on alveolar macrophages from patients with
chronic obstructive pulmonary disease. European J Med
Res 2009; 14(4):1-5.
https://doi.org/10.1186/2047-783X-14-S4-205
21. Cermelli C, Fabio A, Fabio G, Quaglio P. Effect of
eucalyptus essential oil on respiratory bacteria and viruses.
Curr Micro 2008; 56(1):89-92.
https://doi.org/10.1007/s00284-007-9045-0
22. Schnitzler P, Schön K, Reichling J. Antiviral activity of
Australian tea tree oil and eucalyptus oil against herpes
simplex virus in cell culture. Die Pharmazie 2001;
56(4):343-347. PMID: 11338678
23. Vimalanathan S, Hudson J. Anti-influenza virus activity of
essential oils and vapors. American J Essent Oils Nat Prod
2014;2(1):47-53.
24. Vail III WB, Vail ML. Methods and apparatus to prevent,
treat and cure infections of the human respiratory system
by pathogens causing severe acute respiratory syndrome
(SARS). Google Patents; 2006.
25. Mulyaningsih S, Sporer F, Reichling J, Wink M.
Antibacterial activity of essential oils from Eucalyptus and
of selected components against multidrug-resistant
bacterial pathogens. Pharm Biol 2011; 49(9):893-899.
https://doi.org/10.3109/13880209.2011.553625
26. Amini N, Rezaei K, Yazdannik A. Effect of nebulized
eucalyptus on contamination of microbial plaque of
endotracheal tube in ventilated patients. Iranian J Nursing
Midwifery Res 2016; 21(2):165.
https://doi.org/10.4103/1735-9066.178242
27. Suman A, Chauhan S, Lata S, Sharma RK. Antifungal
activity of various plant oils against yeast isolates from
ICU patients. Int J Res Med Sci 2017; 5(7):3227.
https://doi.org/10.18203/2320-6012.ijrms20173018
28. Han X, Parker TL, Dorsett J. An essential oil blend
significantly modulates immune responses and the cell
cycle in human cell cultures. Cogent Biol 2017;
3(1):1340112.
https://doi.org/10.1080/23312025.2017.1340112
29. Serafino A, Vallebona PS, Andreola F, et al. Stimulatory
effect of Eucalyptus essential oil on innate cell-mediated
immune response. BMC Immunol 2008; 9(1):17.
https://doi.org/10.1186/1471-2172-9-17
30. Ingraham NE, Lotfi-Emran S, Thielen BK, et al.
Immunomodulation in COVID-19. The Lancet
Respiratory Medicine 2020;
https://doi.org/10.1016/S2213-2600(20)30226-5
31. Yadav N, Chandra H. Suppression of inflammatory and
infection responses in lung macrophages by eucalyptus oil
and its constituent 1, 8-cineole: Role of pattern recognition
receptors TREM-1 and NLRP3, the MAP kinase regulator
MKP-1, and NFκB. PLoS One. 2017; 12(11):e0188232.
https://doi.org/10.1371/journal.pone.0188232
32. Jun YS, Kang P, Min SS, Lee J-M, Kim H-K, Seol GH.
Effect of eucalyptus oil inhalation on pain and
inflammatory responses after total knee replacement: a
randomized clinical trial. Evidence-Based Com Alt Med
2013. https://doi.org/10.1155/2013/502727
33. Penfold AR. Eucalyptus Oils. Environment: a magazine of
science. 1934; 1(3).
34. Mandal S. Repellent activity of Eucalyptus and
Azadirachta indica seed oil against the filarial mosquito
Culex quinquefasciatus Say (Diptera: Culicidae) in India.
Asian Pac J Trop Biomed 2011;1(1):S109-S112.
https://doi.org/10.1016/S2221-1691(11)60135-4
35. Kutumian DM. Multipurpose cleaner and method of
cleaning using therapeutic grade essential oils. Google
Patents; 2012.
36. Fugh-Berman A. The 5-minute herb and dietary
supplement consult. Lippincott Williams and Wilkins;
2003. https://doi.org/10.4065/78.11.1436-a
37. Organization WH. WHO monographs on selected
medicinal plants. Vol 2. World Health Organization; 1999.
38. Carson C, Riley T, Cookson B. Efficacy and safety of tea
tree oil as a topical antimicrobial agent. J Hospital Inf
1998;40(3):175-178.
https://doi.org/10.1016/S0195-6701(98)90135-9
39. Shalaby SE, El-Din MM, Abo-Donia SA, Mettwally M,
Attia ZA. Toxicological affects of essential oils from
eucalyptus Eucalyptus globules and clove Eugenia
caryophyllus on albino rats. Pol J Environ Stud. 2011;
20(2):429-434.
40. Mathew T, Kamath V, Kumar RS, et al. Eucalyptus oil
inhalation-induced seizure: A novel, under recognized,
preventable cause of acute symptomatic seizure. Epilepsia
Open 2017;2(3):350-354.
https://doi.org/10.1002/epi4.12065
41. Niggemann B, Grüber C. Side effects of complementary
and alternative medicine. Allergy 2003;58(8):707-716.
https://doi.org/10.1034/j.1398-9995.2003.00219.x
42. Devi MP, Chakrabarty S, Ghosh S, Bhowmick N.
Essential oil: its economic aspect, extraction, importance,
uses, hazards and quality. Value addition of horticultural
crops: recent trends and future directions. Springer;
2015:269-278.
https://doi.org/10.1007/978-81-322-2262-0_15
43. Kehrl W, Sonnemann U, Dethlefsen U. Therapy for acute
nonpurulent rhino sinusitis with cineole: results of a
double blind, randomized, placebo controlled trial. The
Laryngoscope 2004;114(4):738-742.
https://doi.org/10.1097/00005537-200404000-00027
44. Tesche S, Metternich F, Sonnemann U, Engelke J-C,
Dethlefsen U. The value of herbal medicines in the
treatment of acute non-purulent rhinosinusitis. European
Arch Oto-rhino-Laryngol2008; 265(11):1355.
https://doi.org/10.1007/s00405-008-0683-z