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Anti-influenza virus activity of essential oils and vapors

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Few satisfactory therapeutic agents are available for the control of Influenza virus, largely because of the continual emergence of drug-resistant mutants. Some essential oils (EOs) have demonstrated effective antimicrobial and antiviral properties in experimental conditions, but most of these studies tested the liquid oil phases, which are generally less practical and are potentially toxic for oral applications. In the present study, we evaluated several EOs and some of their major constituents for their possible anti-influenza virus properties in both liquid and vapor phases. In vapor phase Citrus bergamia, Eucalyptus globulus, and the isolated compounds citronellol and eugenol were very active against influenza virus following exposures of only 10 minutes. Pelargonium graveolens, Cinnamomum zeylanicum, Cymbopogon flexuosus were also very active with 30 minutes exposure. In liquid phase, Cinnamomum zeylanicum, Citrus bergamia, Cymbopogon flexuosus and Thymus vulgaris displayed 100% inhibitory activity at 3.1 µL/mL concentration. Under these conditions the vapors showed no measurable adverse effect on epithelial cell monolayers. This suggests that these oils in their vapor phases could be potentially useful in influenza therapy. The oil vapors were also evaluated for possible direct effects on the principal external proteins of the influenza virus, namely the HA (hemagglutinin) and NA (Neuraminidase). Several of the vapors inhibited the HA activity, but not the NA activity, suggesting that interaction with HA is a possible mechanism for the antiviral activity. Thus some of these oil vapors could have therapeutic benefits for people suffering from influenza, and possibly other membrane containing respiratory viruses.
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American Journal of Essential Oils and Natural Produ cts 2014; 2 (1): 47-53
ISSN: 2321 9114
AJEONP 2014; 2 (1): 47-53
© 2014 AkiNik Publications
Received: 22-06-2014
Accepted: 25-08-2014
Selvarani Vimalanathan
Department of Pathology &
Laboratory Medicine, University
of British Columbia, Vancouver,
BC, V6T 1Z1, Canada.
James Hudson
Department of Pathology &
Laboratory Medicine, University
of British Columbia, Vancouver,
BC, V6T 1Z1, Canada.
Correspondence:
Selvarani Vimalanathan
Department of Pathology &
Laboratory Medicine, University
of British Columbia, Vancouver,
BC, V6T 1Z1, Canada.
Email: vimrani1@mail.ubc.ca
Anti-influenza virus activity of essential oils and vapors
Selvarani Vimalanathan, James Hudson.
Abstract
Few satisfactory therapeutic agents are available for the control of Influenza virus, largely because of
the continual emergence of drug-resistant mutants. Some essential oils (EOs) have demonstrated
effective antimicrobial and antiviral properties in experimental conditions, but most of these studies
tested the liquid oil phases, which are generally less practical and are potentially toxic for oral
applications. In the present study, we evaluated several EOs and some of their major constituents for
their possible anti-influenza virus properties in both liquid and vapor phases. In vapor phase Citrus
bergamia, Eucalyptus globulus, and the isolated compounds citronellol and eugenol were very active
against influenza virus following exposures of only 10 minutes. Pelargonium graveolens,
Cinnamomum zeylanicum, Cymbopogon flexuosus were also very active with 30 minutes exposure. In
liquid phase, Cinnamomum zeylanicum, Citrus bergamia, Cymbopogon flexuosus and Thymus vulgaris
displayed 100% inhibitory activity at 3.1 µL/mL concentration. Under these conditions the vapors
showed no measurable adverse effect on epithelial cell monolayers. This suggests that these oils in their
vapor phases could be potentially useful in influenza therapy. The oil vapors were also evaluated for
possible direct effects on the principal external proteins of the influenza virus, namely the HA
(hemagglutinin) and NA (Neuraminidase). Several of the vapors inhibited the HA activity, but not the
NA activity, suggesting that interaction with HA is a possible mechanism for the antiviral activity.
Thus some of these oil vapors could have therapeutic benefits for people suffering from influenza, and
possibly other membrane containing respiratory viruses.
Keywords: Essential oil, Vapor phase, antiviral activity, Hemagglutination (HA) Inhibition
1. Introduction
Influenza viruses continue to pose threats of epidemics, resulting from mutated viruses, to
which we have inadequate therapeutic remedies, largely because of the continuing emergence
of drug-resistance. Thus alternative therapies, targeting the viruses themselves rather than
their individual genes, could be useful.
Essential oils (EOs) of plants have been used traditionally for numerous applications in
health-related areas, and in foods and commercial uses [1, 2]. In most medical applications the
oils were applied directly to the skin, although the potential cytotoxicity of EOs precluded
internal consumption [3]. This problem could, at least in theory, be avoided by inhalation of
the vapors of EOs, as practiced in aromatherapy. Furthermore in many traditional remedies
for colds and respiratory disorders, formulations often included plant EOs to provide relief
through inhalation of the vapors [3].
Recently a number of studies reported the presence of antimicrobial and antiviral activities in
certain EOs and their components, such as monoterpenes. However, those studies were
carried out with the liquid phases of the oils and their components [3, 4, 5, 6, 7, 8, 9, 10, 11].
In contrast, Inouye et al. [12] Thyagi and Malik [13], Hudson et al. [14] and Vimalanathan and
Hudson [15] demonstrated that the vapor or “gaseous” phase of certain EOs showed good
antibacterial, antifungal and antiviral activity, sometimes better than the corresponding liquid
phase of the oil.
Some studies also indicated that the whole unfractionated oil was as potent as any of the
individual components, suggesting synergism [3 , 10].These observations clearly indicate that,
while there is great potential for the use of EOs as antimicrobials and antivirals, there is still
scope for further evaluation of the optimal methods for their applications.
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In order to address these issues, we compared the anti-
influenza virus activities, and relative cytotoxic potentials, of a
number of commercial EOs, and some of their pure
compounds in their liquid and vapor phases. In addition we
also examined their effects on the influenza neuraminidase and
hemagglutinin, the major viral antigens.
2. Materials and methods
2.1 Test materials
All the essential oils (EOs) were standard commercial brands
purchased from local suppliers (Table 1).
Table 1: Essential oils used and their suppliers, major constituents and references.
Scientific name and family Common name
Supplier and origin Major components
(%) References
Lavandula officinalis
Lamiaceae
Fresh flowering heads
Julia lawless
Aqua Oleum
Bulgaria
Linalyl acetate
Linalool
[24]
Pelargonium graveolens
Geraniaceae
Geranium
Leaves and flowering branchlets
Aura Cacia
China
Citronellol
Geraniol
[25, 26]
Cinnamomum zeylanicum
Lauraceae
Cinnamon leaf oil
Leaves Aura Cacia
Sri Lanka
Eugenol
[23]
Salvia officinalis
Lamiaceae
Sage
Partially dried leaves
Aura Cacia
Austria, Croatia
1,8
Cineole
α-Thujone
[7, 22]
Eucalyptus globulus
Myrtaceae
Eucalyptus
Leaves and twigs
Julia lawless
Aqua Oleum
South Africa
1,8
-
Cineole
α-Pinene
[13]
Cymbopogon flexuosus
Poaceae
Lemongrass
Freshly cut grass
Aura Cacia
India
Geranial
Neral
[27, 28]
Thymus vulga
ris
Lamiaceae
Red Thyme
Partially dried above ground plant parts.
Aura Cacia
Spain
1,8
-
cineole
Terpenyl acetate
Borneol
[21]
Citrus bergamia
Rutaceae
Bergamot
Fruit Peel
Aura Cacia
Italy
(
)
-
linalyl acetate
(–)-linalool
(+)-limonene
γ-Terpinene,
β-Pinene
α-pinene
α-terpinene
[29, 30]
Cupressus sempervirens
Cupressaceae
Cypress oil
Needles & Twigs
Aura Cacia
Morocco
α
-
pinene
α-terpinene
[7]
2.2 Cells and virus
Madin-Darby canine kidney cells (MDCK) and A549 human
lung epithelial cells were acquired originally from ATCC
(American Type Culture Collection, Rockville, MD), and were
passaged in Dulbecco MEM (DMEM), in cell culture flasks,
supplemented with 5% fetal bovine serum, at 37 °C in a 5%
CO2 atmosphere (cell culture reagents were obtained from
Invitrogen, Ontario CA). No antibiotics or antimycotic agents
were used.
Influenza virus A1/Denver/1/57 (H1N1) was acquired from
BC Centre for Disease Control, Vancouver, and was grown in
MDCK cells with TPCK (L-1-Tosylamide-2-phenylethyl
chloromethyl ketone; Sigma Chemical co.) treated trypsin (2
µg/mL) and assayed by plaque formation. The following pure
compounds citronellol and eugenol were kindly supplied to us
by Dr. Murray Isman, University of British Columbia. The
infectious titer of stock virus varied from 105-106 PFU/mL.
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2.3 Virucidal activity (liquid phase)
The assay technique was based on our standard techniques for
the evaluation of plant extracts for antiviral activity [16, 1 7]. The
experimental procedure consisted of incubating two-fold
dilutions of the test oil or compound in phosphate buffered
saline, in 96-well trays, with 20 µL of virus containing 800
plaque forming unit of virus. The mixtures, in triplicate, were
incubated for 60 min at 22 ºC. The total volume of 120 µL
from each mixture was then transferred into confluent MDCK
cells containing 1mL PBS, and incubated at 37 ºC to allow
adsorption of remaining virus. After 60 min the inocula were
removed and replaced with 0.5% agarose in MEM and 2
µg/mL trypsin. Monolayers were fixed with 3.6% formalin
after 48 h and stained with 0.1% crystal violet. Virus plaques
were counted. Inhibitory concentration was calculated as
MIC100 by comparison with untreated virus controls.
2.4 Virucidal activity (vapor phase)
The method used was a modification of the standard plaque
reduction assay described above. Aliquots (20 µL) of virus
(10000 pfu) were individually dried on the underside of the
caps from sterile Eppendorf tubes, within the biosafety cabinet
(10 min). Test oils (250 µL) were carefully added to each tube,
the caps were replaced with caps containing dried virus film
and exposure to oil allowed for 10 or 30 min, at 37 ºC. Caps
were removed again and each dried exposed film was
reconstituted in 1 mL of PBS. All samples (in triplicate) were
then assayed for virus plaque formation in MDCK cells as
described above. Canola oil, which does not inhibit influenza
virus, was used as a negative control. The reduction of viral
titer was quantified and viral infectivity loss due to drying was
determined to be ≤ 1.0 log10. Starting from a titer of 10,000
PFUs, the virus titer was reduced to ± 1,000 PFUs after drying,
before Eos vapor exposure.
2.5 Neuraminidase Assay (liquid phase)
The Amplex Red Neuraminidase (Sialidase) Assay Kit from
Invitrogen (Ontario) was used. Briefly, equal volumes (25 µL)
of two fold dilutions of EOs and virus (1:4 dilution of stock
virus) were mixed and incubated for at 37 °C with continuous
shaking. After 60 min, 50 µL of 2X working solution of 100
μM Amplex Red reagent containing 0.2 U/mL HRP, 4 U/mL
galactose oxidase and 500 μg/mL fetuin was added and the
mixtures incubated overnight. Absorbance (A) was measured
at 550 nm in a plate reader. The percentage of Neuraminidase
inhibition was calculated by the following formula: Avirus-
Atest/Avirus×100.
2.6 Hemagglutination (HA) Inhibition Assay (Liquid and
Vapor phases)
Since all the liquid EOs were toxic to erythrocytes on direct
exposure, HA inhibition was measured only in dried films of
virus exposed to the vapor phases, as described above for
antiviral activity of EO vapors in Eppendorf tubes.
Reconstituted exposed virus (50 µL) were mixed with 50 µL
of 0.75% suspension of human type O Rh+ erythrocytes and
incubated at 22 ºC for 60 min [18]. The hemagglutination
reaction was observed after 60 min incubation.
2.7 Cytotoxicity assay (Liquid and Vapor phases)
The Cell Proliferation Assay Kit (XTT) (ATCC, Manassas,
VA) was used according to the manufacturer’s instructions.
Human lung epithelial cells (A549 cell line) were used as the
indicator cells. The cells (5× 103) were seeded in each well
containing 100 μL of the MEM medium supplemented with
5% FBS in a 96-well plate. Cells were grown for 48 h and the
test materials, prepared as a series of two-fold dilutions in
MEM, without phenol red, were added to the cells and
incubated for 15 min, followed by removal of test material
and incubation for a further 24 h in MEM, followed by
measurement of cell viability. For cytotoxicity of EOs vapor,
monolayers of human lung A549 cells grown to confluence in
6-well trays for 48 hour. For EOs exposure, the media were
removed by aspiration, and the moist cells were exposed to
EOs vapor. Following further 24 h incubation in normal
medium, cell viability was measured. The results were
measured as absorbance at 490 nm in a plate reader, in
comparison with similar cells exposed to medium only.
Cytotoxicity is expressed as the concentration of test sample
inhibiting cell growth by 50% (TC50). All tests were run in
triplicate and mean values recorded.
3. Results
3.1 Antiviral Activities of Liquid Phase EOs
Three of the oils, Cinnamomum zeylanicum, Citrus bergamia
and Thymus vulgaris (Figure 1, 2), were able to completely
inactivate (IC100) the virus at high dilutions, down to <3.1 µL
per mL or less (Figure 3). Lavandula officinalis and
Eucalyptus globulus also showed excellent activity at higher
concentrations, but were much less effective at the lower
concentrations. Salvia was only partly active at the
concentrations tested. In similar experiments liquid phase
Pelargonium graveolens (Geranium) oil also showed good
antiviral activity. Cupressus sempervirens and its main
constituent α-pinene did not show antiviral activity even at
very low dilutions. Among the pure components tested, only
eugenol showed 100% plaque reduction (Figure 3) but
citronellol displayed partial inactivation. Liquid canola oil,
used as a negative control, had no activity even at very high
concentration (100%)
Fig 1: Antiviral Activities of serial dilutions of EOs. Each sample, in
triplicate, was serially diluted 2x and incubated with a standard
amount of H1N1 virus (800 pfu per reaction). Remaining infectious
viruses were measured by plaque assay on MDCK cells.
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Fig 2: Antiviral Activities of serial dilutions of EOs. Each sample, in
triplicate, was serially diluted 2x and incubated with a standard
amount of H1N1 virus (800 pfu per reaction). Remaining infectious
viruses were measured by plaque assay on MDCK cells.
Fig 3: Antiviral Activities of EOs and selected monoterpenes against
H1N1 virus with 3.1 µL/mL. Each sample, in triplicate, was diluted
to 3.1 µL/mL and incubated with a standard amount of H1N1 virus
(800 pfu per reaction). Remaining infectious viruses were measured
by plaque assay on MDCK cells. Results are expressed as percentage
of plaque reduction.
3.2 Antiviral Activities of EO Vapor Phases
Two EOs, C. bergamia, E. globulus, and the tested pure
compounds citronellol and eugenol showed significant activity
against influenza virus following exposures of only 10
minutes.
Several of the oil vapor phases were able to completely
inactivate influenza virus following exposures of 30 minutes,
as shown in Figure 4. These were, C. zeylanicum, C.
flexuosus, L. officinalis and P. graveolens. T. vulgaris and S.
officinalis showed only partial activity, and the two negative
controls, olive oil and canola oil, showed no antiviral activity.
Thus the relative activities did not reflect the corresponding
activities of the liquid phases.
Fig 4: Antiviral Activities of EOs in vapor phase. Aliquots of
influenza virus, in triplicate dried films of H1N1 virus (1000 pfu of
H1N1 per reaction) were exposed to EO vapors for 10 and 30
minutes, reconstituted in PBS, and remaining infectious viruses
measured by plaque assays on MDCK cells.
3.3 Activities Against Viral HA (Hemagglutinin) and NA
(Neuraminidase)
HA and NA are the two most important proteins of the
influenza virus which together determine successful infection
and dissemination of the virus.
Most of the oil vapors tested showed anti-hemagglutination
activity against the indicator human erythrocytes type O Rh+,
as shown in Table 2 and Figure 5. Since most of the tested Eos
in liquid phase had hemolytic effect, that disabled further
testing of HAI assay with liquid oils.
In contrast to the anti-HA activities, most of the oils, even in
liquid phase, were not able to inhibit NA activity, as shown in
Figure 6. The exception was Cinnamomum zeylanicum, which
showed complete inhibition at least down to 1.5 µL/mL. The
positive control anti-influenza compound zanamivir was
effective as expected.
Human lung epithelial cells (A549) were exposed to EOs for
15 min, followed by incubation in normal medium for 24 h.
They were then assayed for cell viability. Results are shown in
Table 3. All the EOs showed some toxicity at the high
concentrations but were non-toxic at concentrations less than
10 µL/mL. The 24 hour exposures showed greater degrees of
cytotoxicity, except for olive oil, which remained non-
cytotoxic.
In contrast to the results with the liquid phases, when cell
monolayers were exposed to each of the oil vapors for 10 or
30 min there were no adverse effects on cell appearance or
viability, as determined by XTT measurements.
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Fig 5: Viral HAI Assay plate. Inhibitory activity of EOs’ vapor on agglutination with viral hemagglutinin and human type O Rh+ erythrocytes,
as described in Methods (and in WHO Manual, 2011). The presence of conspicuous red buttons in the well indicates absence of agglutination,
i.e. inhibition of HA activity. The other wells show normal hemagglutination.
Fig 6: Effect EOs and zanamivir on the influenza virus Neuraminidase activity. Only the Cinnamon and the positive control zanamivir were
active.
Table 2: Inhibitory activity of EO vapors on agglutination with viral
hemagglutinin and human RBC O Rh+.
EOs vapor
Hemagglutination
inhibition activity (HAI)
C. bergamia
+
C. fle
xuosus
+
C. sempervirens
-
C. zeylanicum
+
E. globulus
+
L. officinalis
-
P. graveolens
+
S. officinalis
+
T. vulgaris
+
Olive oil
-
Virus control
-
Cell control
+
Table 3: TC50 values of EOs in human lung epithelial cells.TC50 =
50% tissue culture cytotoxicity, or concentration giving 50%
reduction in cell viability
Eos liquid
TC
50
Viability (µL/mL)
Citrus bergamia
15.98±6.92
Cymbopogon flexuosus
12.21±2.64
Cupressus sempervirens
75±7.98
Cinnamomum zeylanicum
Eucalyptus globulu
s
26.51± 4.9
Lavandula officinalis
26.46± 3.9
Pelargonium graveolens
67.46± 6.85
Salvia officinalis
26.85± 7.2
Thymus vulgaris
14.34± 3.32
Olive oil
>100±0
Cell control
100
All EO vapors
No cytotoxicity
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4. Discussion
Respiratory viruses continue to cause problems within the
general population, as a result of frequent acute and chronic
infections, including occasional epidemics. Few satisfactory
therapeutic agents are available, in part because of the
diversity of replication schemes among these viruses, and
consequently the lack of a generic molecular target; and partly
because of the continual emergence of drug-resistant mutants
in the viral populations. These problems are well illustrated by
influenza viruses.
Some essential oils have demonstrated effective antimicrobial
and antiviral properties, and in a few cases beneficial anti-
inflammatory properties [4, 8, 19, 6, 3, 20]. However, these studies
tested the liquid oil phases, which are generally less practical
and potentially toxic for nasopharyngeal or oral applications.
A few reports have indicated that the vapors of some oils
might be useful for this purpose [3 , 13, 14 ], and this type of
application would be in accord with anecdotal reports of the
usefulness of inhaled vapors [3, 14].
In the present study we evaluated several essential oils (EOs)
for their possible anti-influenza virus properties under
conditions that are relevant to potential applications. Four of
the EOs, Cinnamomum zeylanicum, Citrus bergamia and
Thymus vulgaris were very active against influenza virus at
relatively low concentrations (MIC100 3.1 µL/mL) in the liquid
phase, but only Citrus bergamia showed prominent activity
(95% ± 2) in its vapor phase (10 min exposure), the rest
showed activity only after 30 min exposure. On the other hand,
Eucalyptus globulus had less activity (MIC100 50 µL/mL) in
liquid phase but showed prominent activity in 10 min vapor
phase (94% ± 3). Interestingly, although 1,8-cineole is the
major component [ 13, 21, 7, 22] of Eucalyptus globulus, Thymus
vulgaris and Salvia officinalis, only Eucalyptus globulus and
Thymus vulgaris exhibited antiviral activity, suggesting that
1,8- cineole might not be responsible for the antiviral property
of Eucalyptus globulus and Thymus vulgaris.
Under these conditions the vapor showed no measurable
adverse effect on epithelial cell monolayers. This suggests that
these oils in their vapor phases could be potentially useful in
influenza therapy. In addition Cinnamomum zeylanicum and
Thymus vulgaris were also very active in the liquid phase,
although they were only partially effective in the vapor phase.
However eugenol, the major component [23] of Cinnamomum
zeylanicum possessed the most potent anti-influenza activity in
both liquid and vapor phases. This suggests that eugenol might
be one of the major components responsible for antiviral
property of Cinnamomum zeylanicum.
Conceivably a longer exposure to these oil vapors could result
in complete virus inactivation. In contrast Salvia officinalis
displayed only slight antiviral activity, only 20% plaque
reduction following 30 minutes exposure. Cupressus
sempervirens oil did not show any activity, this may be
correlated to the inactivity of the main component α-pinene in
both phases. Liquid canola oil, included as a negative control
[19] showed no activity.
The oils were also evaluated for possible direct effects on the
principal external proteins of the influenza virus, namely the
membrane proteins HA (hemagglutinin) and NA
(Neuraminidase). It was not possible to test the liquid oils
against HA because all of them lysed the indicator
erythrocytes. However, we were able to evaluate the vapors,
which did not affect the integrity of the test erythrocytes, and
in this situation most of the oil vapors inhibited viral HA
activity, with the exception of Lavandula officinalis.
In contrast none of the liquid oils, except Cinnamon, were
able inhibit NA activity. This suggests that a primary target
for most of the oils is the viral HA, and this activity was
demonstrated with the EO vapors. However Cinnamon may
be able to target both external proteins. Since the HA and NA
proteins of influenza virus are responsible for virus entry and
exit into and from cells respectively, then inhibition of either
of these viral functions would decrease the growth and
dissemination of the virus.
Most of the liquid phase oils showed cytotoxic effects in
human lung epithelial cells, but in contrast the vapor phases
did not appear to show adverse effects following exposures of
at least 10 minutes.
5. Conclusion
Several of the essential oil vapors evaluated possess potent
anti-influenza virus activity, under conditions that did not
adversely affect cultured epithelial cells. The hemagglutinin
protein of the virus appeared to be a major target. Thus some
of these oil vapors could have therapeutic benefits for people
suffering from influenza, and possibly other respiratory
viruses.
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... [10][11][12] E. purpurea also has antifungal, antiviral, antibacterial, anti-inflammatory, antioxidant, and even cancer-fighting properties. [13][14][15] Therefore, the purpose of this study was to see if E. purpurea root extract might protect against nephrotoxicity, oxidative stress, biochemical and molecular alterations as well as histological and ultrastructural changes caused by hexavalent chromium. ...
Article
Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with the overproduction of free radicals, which induces oxidative damage. Echinacea purpurea (L.) Moench is an herbaceous perennial plant rich in phenolic components and frequently used for its medicinal benefits. The current work evaluated the effectiveness of E. purpurea (EP) against oxidative stress and nephrotoxicity induced by potassium dichromate in male rats. Male Wistar rats were divided into four groups: control, E. purpurea (EP; 50 mg/kg; once daily for 3 weeks), hexavalent chromium (Cr(VI); 15 mg/kg; single intraperitoneal dose), and EP + Cr(VI) where rats were pretreated with EP for 3 weeks before receiving CrVI, respectively. Results revealed that rats exposed to Cr(VI) showed a significant increase in PC, TBARS, and H2O2, kidney function biomarkers (Urea, creatinine, and uric acid), lactate dehydrogenase activity (LDH), TNF‐α, IL‐18, nuclear factor kappa B (NFκB), and IGF‐1 (Insulin‐like growth factor‐1) levels as well as a considerable decline in metallothionein (MT), glutathione (GSH) content, enzymatic antioxidants (SOD, CAT, GPx, GR, and GST), alkaline phosphatase (ALP) activities, and protein content. Cr(VI) induced apoptosis in kidney tissues as revealed by upregulation of Bax and caspase 3 and downregulation of Bcl‐2. Furthermore, EP treatment ameliorated the Cr(VI)‐induced histopathological and ultrastructure variations of kidney tissue, which was confirmed by the biochemical and molecular data. It is clear from the results of this study that EP exerts nephroprotective effects by improving the redox state, suppressing inflammatory reaction and cell apoptosis as well as ameliorating the performance of kidney tissue architecture, which is eventually reflected by the improvement of kidney function in rats.
... Essential oil from Lemongrass (C. citratus) has been shown to exhibit anti-influenza activities [117]. Berberine, an alkaloid from B. vulgaris, has been found to significantly reduce RSV replication by reducing the synthesis of mRNA and viral proteins [118,119]. ...
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Objectives The recent emergence of the COVID-19 pandemic (caused by SARS-CoV-2) and the experience of its unprecedented alarming toll on humanity have shone a fresh spotlight on the weakness of global preparedness for pandemics, significant health inequalities, and the fragility of healthcare systems in certain regions of the world. It is imperative to identify effective drug treatments for COVID-19. Therefore, the objective of this review is to present a unique and contextualised collection of antiviral natural plants or remedies from the West African sub-region as existing or potential treatments for viral infections, including COVID-19, with emphasis on their mechanisms of action. Evidence acquisition Evidence was synthesised from the literature using appropriate keywords as search terms within scientific databases such as Scopus, PubMed, Web of Science and Google Scholar. Results While some vaccines and small-molecule drugs are now available to combat COVID-19, access to these therapeutic entities in many countries is still quite limited. In addition, significant aspects of the symptomatology, pathophysiology and long-term prognosis of the infection yet remain unknown. The existing therapeutic armamentarium, therefore, requires significant expansion. There is evidence that natural products with antiviral effects have been used in successfully managing COVID-19 symptoms and could be developed as anti-COVID-19 agents which act through host- and virus-based molecular targets. Conclusion Natural products could be successfully exploited for treating viral infections/diseases, including COVID-19. Strengthening natural products research capacity in developing countries is, therefore, a key strategy for reducing health inequalities, improving global health, and enhancing preparedness for future pandemics. Graphical abstract
... Another key strategy of antiviral activity is protein inhibition. Generally, viral surface proteins (such as hemagglutinin) help in the attachment and invasion of the virus in the host cell, while some other proteins (Tat protein) help in viral transcription [79]. Recently, it has been reported that cedar leaf essential oils hinder the hemagglutinin protein, while thyme essential oils destabilize the Tat protein [80,81]. ...
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With the onset of the COVID-19 pandemic in late 2019, and the catastrophe faced by the world in 2020, the food industry was one of the most affected industries. On the one hand, the pandemic-induced fear and lockdown in several countries increased the online delivery of food products, resulting in a drastic increase in single-use plastic packaging waste. On the other hand, several reports revealed the spread of the viral infection through food products and packaging. This significantly affected consumer behavior, which directly influenced the market dynamics of the food industry. Still, a complete recovery from this situation seems a while away, and there is a need to focus on a potential solution that can address both of these issues. Several biomaterials that possess antiviral activities, in addition to being natural and biodegradable, are being studied for food packaging applications. However, the research community has been ignorant of this aspect, as the focus has mainly been on antibacterial and antifungal activities for the enhancement of food shelf life. This review aims to cover the different perspectives of antiviral food packaging materials using established technology. It focuses on the basic principles of antiviral activity and its mechanisms. Furthermore, the antiviral activities of several nanomaterials, biopolymers, natural oils and extracts, polyphenolic compounds, etc., are discussed.
... In fact, many compounds extracted from plants have known antiviral activity. Volatile compounds such as monoterpenes, sesquiterpenes and diterpenes are among the secondary metabolites having this activity (Adorjan and Buchbauer, 2010;Da Silva et al., 2014;Vimalanathan and Hudson, 2014;Shakeri et al., 2017). ...
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Context: COVID-19 is a pandemic that has affected the entire population, characterized by multisystemic involvement. With around 130 million cases of infection and more than 2.5 million deaths globally. However, the development of a low-efficacy treatment has led to the study of natural products as possible therapeutic alternatives against SARS-CoV-2. Aims: To identify volatile compounds present in two plants in the Colombian Pacific and carry out in-silico studies to search for promising inhibitory molecules against SARS-CoV-2 proteases. Methods: This research carried out the identification of metabolites of two plants identified in the Colombian Pacific, called P. scaberrima (Juss. ex Pers.) Moldenke y D. ambrosioides (L.) Mosyakin & Clemants. Ethanolic extracts were obtained by rotary-evaporation and determinated by GC-MS. Subsequently, in-silico studies were carried out by molecular docking against Mpro and PLpro using Autodock-vina 1.1. Also, a prediction of ADMET properties using SwissADME and GUSAR-Online server was performed. Results: Thus, 15 volatile compounds with similarities greater than 85% were identified from both extracts, mostly sesquiterpenic and monoterpenic compounds. The compounds that showed the highest affinity against Mpro were α-amorphene and phytol for PLpro. Likewise, these were contrasted with co-crystallized molecules such as boceprevir and VIR2-251 as control structures. Finally, the predictions of ADMET properties showed values consistent with the literature. Conclusions: Therefore, the follow-up of in-silico studies with these plants from Colombian pacific are considered as possible tools in the search for active molecules against proteases linked to virus.
... But the role that each individual component plays in the overall EO antiviral activity is source of controversy. Indeed, (Vimalanathan and Hudson, 2014) reported that Eucalyptus globulus and Salvia officinalis both contain1,8-cineole as a major component. However, the former was reported to have strong anti-H1N1 activity (IC 50 < 3.1 μg/mL) while the later was not. ...
Article
To investigate chemical compositions and antiviral activities of essential oils (EOs) from two Ivorian aromatic plants (Lippia multiflora and Zingiber officinale) against two non-enveloped viruses (PV-1 and enterovirus type 1), human enteroviruses, chemical composition of LMEO and ZOEO was obtained by GC-MS. Biological activities such as inhibitory action on α-glucosidase, α-amylase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase and antioxidative potential of both EOs were evaluated. Respective cytotoxicity of LMEO and ZOEO towards RD (rhabdomyosarcoma) and L20B (a genetically engineered mouse cell line) were also determined by observation of the cell line carpet. In addition, Antiviral activity of LMEO and ZOEO against poliovirus type I and enterovirus type I was assessed using a cell culture cytopathic inhibition test. From the structure elucidation experiment, a total number of 23 and 30 compounds were respectively identified for LMEO and ZOEO. Among both plant species, ZOEO significantly inhibited type I enterovirus activity by 50% at 9.860 µg/mL as compared to LMEO (44.47 µg/mL), respectively after 48 and 72 h of incubation. Furthermore, inhibition was statistically the same for studied essential oils (ZOEO: 9 µg/mL and LMEO: 9.077 µg/mL). As a result of our findings, we concluded that the tested essential oils could be used as a source of natural antiviral agents in phytotherapeutic applications.
... The EO of C. zeylanicum was found to have a 100% inhibitory effect on influenza virus A1/Denver/1/57 (H1N1) with a 30-minute exposure at a concentration of 3.1 µL/mL. As a result of this study, Eugenol, the main component of C. zeylanicum EO, was reported to have the strongest anti-flu activity in both liquid and vapor phases (Vimalanathan at al., 2014). ...
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It is the ability of an implant to respond appropriately to the body. If it is biomaterial; It is defined as a material with biocompatibility. Biocompatibility is the most important feature of a biomaterial besides its strength. A biocompatible material does not harm the surrounding tissue in the body, does not develop a reaction and is integrative. Biocompatibility is the physical, chemical and biological compatibility of a biomaterial to body tissues and the Implants can be classified as bioactive, biotolerant and bioinert according to their biocompatibility. Ceramics such as calcium hydroxyapatite are bioactive materials. Calcium hydroxyapatite coated implants are attached to the mineralized bone matrix through chemical reactions(1).For this reason, they are used as artificial bone in the construction of various prostheses, in the repair of cracked and broken bones, and in the coating of metallic biomaterials.
... 23 . In vapor phase, Eucalyptus oil and its main compound eugenol are effective against influenza virus 21 . Eucalyptus oil can affect the innate cell-mediated immune response. ...
... One study has shown the in vitro antiviral effect of essential oil of L. angustifolia against influenza type A (H1N1) (Vimalanathan and Hudson, 2014). The effect of lavender on COVID-19 virus should be evaluated in future studies. ...
Article
Objective: The effect of lavender syrup on COVID-19-induced olfactory dysfunction (OD) has been assessed in this study. Materials and methods: This pilot clinical trial was conducted in Gonbad-E-Kavoos (Golestan province, Iran). Twenty-three outpatients with COVID-19 and OD in lavender group took 9 ml of lavender syrup/bid for 3 weeks along with the standard COVID-19 treatments and 20 patients in control group took only standard COVID-19 treatments. The severity of OD was assessed by the visual analogue scale (VAS). Data analysis was performed by Friedman and Mann-Whitney tests using SPSS software. Results: The mean± standard deviation of age was 36.6±9.1, and 42.6±10.4 years (p=0.05), and the duration of symptoms was 7.4±3.5, and 7.5±3.4 days (p=0.98) in the lavender and control group, respectively. The VAS score for OD decreased from 6.8±3.04 to 0.26±0.86 in the lavender group and from 5.3±3.4 to 1±2.61 in the control group. Although, VAS for OD was significantly decreased in both groups (p<0.001), the amount of VAS decrease was 6.6±2.9 scores in the lavender group, and 4.3±4 in the control group (p=0.03). No side effects were observed in the lavender group. Conclusion: The present study showed that lavender syrup is an effective treatment for COVID-19-induced OD. It is suggested to conduct further studies with larger sample size.
... Thus, it can be presumed that this was very active in its liquid phase and partially active in its vapour phase. Furthermore, cinnamon could target both the external proteins Haemagglutinin (HA) and Neuraminidase (NA) which are responsible for virus entry and multiplication ultimately decreasing the growth and dissemination of the virus (Selvarani and Hudson, 2014) [57] . AgNPs derived from C. cassia extract inhibited avian influenza virus subtype H7N3 with non-cytotoxic effect even at 500 µg/ml and attested its efficacy as natural antiviral drug (Fatima et al., 2016) [25] . ...
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Synthetic antiviral medicines expounded for treating infective agent diseases expose a variety of undesirable consequences on mortals necessitating the contribution of natural medication and medicines of plant origin. Husbandry crops implementing the intent of protecting foods have the competency to contend microorganism, plant and infective agent diseases debilitative human health. Spices are well-utilized by our ancestors for formulating medicines to cure many health ailments therefore reassuring its ability to fight the frightful infective agent diseases. This manuscript solely congregates the Phyo-pharmaceuticals nonheritable in spices impartation protection against animal virus, picornavirus, influenza, dengue, chikungunya, zika, etc. which might be exposed to additional analysis in medical environment to confront the most recent severe COVID-19 still as imminent frailties all the way down to budding viruses.
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1,8-cineole is a licensed medicinal product formulated in gastric resistant capsules (200 mg/capsule) in Germany due to its negligible side effects. It is a strong helper against the agonizing symptoms of bronchitis, common colds, and respiratory tract influenza. Additionally, 1,8-cineole is well known for its mucolytic and spasmolytic action on the respiratory tract with proven clinical efficacy. The medicine has also shown therapeutic benefits in inflammatory airway diseases in reducing excessive immune reactions in various preclinical investigations. Therefore, 1,8-cineole can be a good medical candidate against COVID-19 variant omicron, which triggers milder illness with symptoms such as cough, fever, and fatigue in the majority of those it infects. The medicine can keep the airways of patients suffering from respiratory diseases free for breathing. 1,8-cineole can help the patients wining enough time to build antibodies against COVID-19 variant omicron through their immune systems.
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The demand for lemongrass (Cymbopogon citratus) is for its high citral content. Early or delayed harvesting of lemongrass affected essential oil and citral content. The objective of the study was to determine the effects of three maturity stages at harvest of lemongrass on essential oil, chemical composition and citral contents. The lemongrass plant was planted using a randomized complete block design with four replications, at the University Agriculture Park, Universiti Putra Malaysia. The plants were harvested at 5.5, 6.5, and 7.5 months after planting. After harvest, the essential oil, chemical composition and citral contents were analysed using gas chromatography-mass spectrometry (GC-MS) analysis. There were significant effects of maturity stages on essential oil and citral contents. Lemongrass harvested at 5.5 and 6.5 months after planting had significantly higher oil contents than those harvested at 7.5 months. A total of 65 compounds were detected from all the three stages of maturity. However, only 13 compounds were present at each of the maturity stage. Among 13 compounds, only 7 compounds (β-myrcene, 3-undecyne, neral, geranial, nerol, geranyl acetate and juniper camphor) had a concentration of greater than 1%. The citral content at 6.5 months after planting was higher by 11.4% than at 5.5 months after planting. The citral content decreased by 5.4% when lemongrass was harvested at 6.5 compared to at 7.5 months after planting. Citral content peaked at 6.7 ± 0.3 months after planting. Thus, maturity stage at harvest influenced essential oil and citral contents of lemongrass. Therefore, lemongrass should be harvested at the appropriate level of maturity in order to achieve high quality essential oil and lower production cost.
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The essential oils of the bark, leaf, root and fruit of Cinnamon were analyzed by capillary GC and GCIMS. The major constituents of Cinnamon fruit oil, were 6-and y-cadinene (36.0%) and T-cadinol (7.7%) and 8-caryophyllene (5.6%). About 84% of Cinnamon fruit oil comprised sesquiterpenes while other parts of Cinnamon contained less than 9% of this group of compounds. Phenyl propanoids were the major constituents of Cinnamon bark and leaf oils while root oil had monoterpenes as the major constituents (95%).
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The chemical composition of essential oils and hydrolate from dried lavender flowers (Lavandula angustifolia) was determined. Organic compounds were isolated from the hydrolate by the liquid–liquid (LLE) method. Optimal conditions for LLE (pentane, five extraction cycles, 40 mL, salting out [5% NaCl]) were determined by the Taguchi method. As many as forty-seven compounds were identified both in the essential oil (Oe) and in the essential oil isolated during the preparation of hydrolate (OeH), representing 94.9% of the content of Oe and 95.7% of OeH. The main compounds in OeH and Oe are: linalool (24.6% and 24.9%, respectively), linalyl acetate (14.4% and 18.0%, respectively) and borneol (6.2% and 6.3%, respectively). The most abundant compounds are oxygenated derivatives of monoterpenes (74.3% Oe, 73.4% OeH), including monoterpene alcohols (40.5% Oe, 38.0% OeH). In the hydrolate (H), twenty-four compounds, representing 83.8% of its composition, were identified. The main ingredients are: linalool (26.5%) and borneol (9.0%). Also here, oxygenated derivatives of monoterpenes predominate (78.1%), consisting mainly of alcohol monoterpenes (50.7%). In the hydrolate, the presence of acetate linalyl, monoterpenes, or sesquiterpenes was not found. Quantitative analysis of Oe, OeH and H was conducted for selected chemical compounds.
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The essential oil and various extracts obtained from Salvia cedronella Boiss have been evaluated for their possible in vitro antimicrobial and antiviral capacities. The GC-EIMS analysis of the essential oil was resulted in detection of 92 components representing 96.1% of the oil. Major components were 1,8- cineole, α α α α-pinene, caryophyllene oxide and sabinene. In the case of antimicrobial activity, hexane and dichloromethane extracts did not show any effects. Methanolic extract and essential oil exhibited various degrees of activity against the tested microorganisms. The antiviral potential of the plant samples was screened in 2 model systems namely; reproduction of 2 influenza viruses in MDCK cells and of 2 herpes simplex viruses in MDBK cells. The methanol extract showed a good anti-influenza virus effect, the growth of both A/Weybridge and A/Aichi was reduced significantly. This extract also exhibited anti-herpetic activity. Amount of the total phenolics was very high in methanol extract. It was followed by dichloromethane. This extract has also been found to be rich in flavonoids. A positive correlation was observed between biological activity potential and amount of phenolic compounds of the extracts.
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Commercial Oregano oils with high concentrations of carvacrol have been vigorously promoted as antiviral agents effective against colds and ‘flu, including the pandemic H1N1 virus. However there seems to be no evidence to support these claims. Furthermore, since carvacrol itself is known to be toxic, so-called “carrier oils”, such as olive oil, have been included in formulations to ameliorate the potential toxic effects. We compared the anti- influenza virus activity of several preparations, with and without “carriers”, and pure olive oil and carvacrol, by means of quantitative assays for H1N1 influenza virus, and for cytotoxicity in human lung epithelial cells. A range of concentrations was evaluated, including those relevant to consumer applications. All five Oregano oils showed significant antiviral activity, as did olive oil by itself, although their potencies were not comparable to a standardized preparation of Echinacea purpurea. Carvacrol was also very active, but it was also strongly cytotoxic. In addition all the Oregano oils were more cytotoxic than Echinacea purpurea. Thus certain commercial Oregano oils do possess anti-influenza virus activities, although these are less than a potent standardized Echinacea preparation, and furthermore the toxicity of the oils to lung epithelial cells, at doses relevant to consumer applications, is a limiting factor in their usefulness for oral applications.
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Respiratory viruses continue to cause frequent acute and chronic infections, for which few satisfactory treatments are available. Some essential oils possess antiviral properties, but these have usually been tested as liquids, which have limited applications. In this study the vapor of cedar leaf oil (CLO vapor) was evaluated for antiviral activity, in addition to its possible anti-inflammatory activity. The viruses tested, Influenza viruses, Rhinovirus, Adenovirus, and Herpes simplex viruses 1 and 2, in the form of dried films, were all inactivated by exposure to CLO vapor. In assays for influenza viral hemagglutinin (HA) the HA activity was inhibited by CLO vapor. Exposure of human lung epithelial cell monolayers to the vapor showed inhibition of rhinovirus virus-induced cytokine IL-6, but the cells themselves were not adversely affected by short exposure to the vapor. However the two major volatile components of CLO, thujone and alpha - pinene, did not show activity against influenza viral infectivity or hemagglutinin, indicating possible synergistic effects of the whole vapor. We conclude that CLO vapor has potential applications in the control of viral respiratory infections.
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The chemical constituents of the essential oil Pelargonium graveolens leaves were analyzed by GC and GC-MS. Thirty compounds accounting for 99.1% of the oil were identified. The main components identified were citronellol (33.6%), geraniol (26.8%), linalool (10.5%), citronellyl formate (9.7%) and p-menthone (6.0%).
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Leaf oils of Cymbopogon flexuosus and Cymbopogon tortilis were submitted to combined analysis by CG(retention indices), Gas Chromatography Mass Spectrometry (GC-MS), and C Nuclear Magnetic Resonance (NMR). The composition was dominated by geranial (39.2% and 32.0%) and neral (24.1% and 19.1%). Cis- and trans-7-hydroxy-3,7-dimethyl-3,6-oxyoctanal (synonym: cis- and trans-tetrahydro-5-(1-hydroxy-1-methylethyl)-2-methyl-2-furanacetaldehyde) were identified by C NMR by comparison with literature data.