Download full-text PDF

Pharmaceutical and Therapeutic Potentials of Essential Oils and Their Individual Volatile Constituents: A Review

Article · Literature Review (PDF Available) inPhytotherapy Research 21(4):308-23 · April 2007with2,571 Reads
DOI: 10.1002/ptr.2072} · Source: PubMed
Abstract
Essential oils and their volatile constituents are used widely to prevent and treat human disease. The possible role and mode of action of these natural products is discussed with regard to the prevention and treatment of cancer, cardiovascular diseases including atherosclerosis and thrombosis, as well as their bioactivity as antibacterial, antiviral, antioxidants and antidiabetic agents. Their application as natural skin penetration enhancers for transdermal drug delivery and the therapeutic properties of essential oils in aroma and massage therapy will also be outlined.
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 1
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
Copyright © 2007 John Wiley & Sons, Ltd.
PHYTOTHERAPY RESEARCH
Phytother. Res. (in press)
Published online in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/ptr.2072
REVIEW ARTICLE
Pharmaceutical and Therapeutic Potentials of
Essential Oils and Their Individual Volatile
Constituents: A Review
Amr E. Edris*
Aroma and Flavor Chemistry Department, National Research Center, Dokki, El Behose Street, Dokki, 12622, Cairo, Egypt
Essential oils and their volatile constituents are used widely to prevent and treat human disease. The possible
role and mode of action of these natural products is discussed with regard to the prevention and treatment of
cancer, cardiovascular diseases including atherosclerosis and thrombosis, as well as their bioactivity as antibac-
terial, antiviral, antioxidants and antidiabetic agents. Their application as natural skin penetration enhancers
for transdermal drug delivery and the therapeutic properties of essential oils in aroma and massage therapy
will also be outlined. Copyright © 2007 John Wiley & Sons, Ltd.
Keywords: essential oils; cancer; cardiovascular disease; antimicrobial; antidiabetic; penetration enhancer; aromatherapy; massage
therapy.
Received 6 December 2005
Revised 31 October 2006
Accepted 31 October 2006
* Correspondence to: Amr E. Edris, Aroma and Flavor Chemistry De-
partment, National Research Center, Dokki, El Behose Street, Dokki,
12622, Cairo, Egypt.
E-mail: amr_edris@hotmail.com
INTRODUCTION
Aromatic plants had been used since ancient times
for their preservative and medicinal properties, and
to impart aroma and flavor to food. Hippocrates,
sometimes referred to as the ‘father of medicine’, pre-
scribed perfume fumigations.
The pharmaceutical properties of aromatic plants are
partially attributed to essential oils. The term ‘essential
oil’ was used for the first time in the 16th century
by Paracelsus von Hohenheim, who named the effec-
tive component of a drug, ‘Quinta essential’ (Guenther,
1950). By the middle of the 20th century, the role
of essential oils had been reduced almost entirely to
use in perfumes, cosmetics and food flavorings, while
their use in pharmaceutical preparations had declined.
Essential oils are natural, complex, multi-component
systems composed mainly of terpenes in addition to
some other non-terpene components. Several techniques
can be used to extract essential oils from different parts
of the aromatic plant, including water or steam distilla-
tion, solvent extraction, expression under pressure,
supercritical fluid and subcritical water extractions.
ESSENTIAL OILS AND CANCER
Most cancer chemotherapy regimens make use of highly
cytotoxic drugs that target proliferating cell populations.
The non-discriminatory nature of these drugs leads to
severe side effects in normal cells with a high prolifera-
tive index, such as those of the gastrointestinal tract
and bone marrow, thus limiting the effective dose of
anticancer drug that can be administered. The diverse
therapeutic potential of essential oils has drawn the
attention of researchers to test them for anticancer
activity, taking advantage of the fact that their mecha-
nism of action is dissimilar to that of the classic cytotoxic
chemotherapeutic agents (Rajesh et al., 2003). Early
reports had indicated that essential oil components,
especially monoterpenes, have multiple pharmacolo-
gical effects on mevalonate metabolism which could
account for the terpene-tumor suppressive activity
(Elson, 1995).
Monoterpenes have been shown to exert chemopre-
ventive as well as chemotherapeutic activities in
mammary tumor models and thus may represent a new
class of therapeutic agents. The mechanism of action
of monoterpenes is based on two main approaches,
chemoprevention and chemotherapy. Chemoprevention
occurs during the initiation phase of carcinogenesis
to prevent the interaction of chemical carcinogens with
DNA, by induction of phase I and phase II enzymes
to detoxify the carcinogen (Wattenberg, 1992). Chemo-
therapy works during the promotion phase, in which
inhibition of tumor cell proliferation, acceleration of
the rate of tumor cell death and/or induction of tumor
cell differentiation may occur (Morse and Stoner, 1993).
Chemoprevention
It is generally accepted that components that induce
Phase I or II drug metabolizing enzymes can protect
against chemical carcinogenesis or damage, especially
during the initiation phase. Essential oils could be
utilized to protect body organs against carcinogenesis;
for instance, nutmeg, (Myristica fragrans), showed a
potent hepatoprotective activity against liver damage
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
2A. E. EDRIS
caused by certain chemicals (Morita et al., 2003). The
protective activity was correlated with myristicin, a
major constituent. The mechanism of hepatoprotective
activity of myristicin includes inhibition of TNF-
α
release from macrophages and suppression of apoptosis.
Myristicin can also induce glutathione-S-transferase,
a phase II detoxifying enzyme (Ahmad et al., 1997),
in addition to its activity of inhibiting benzo[a]pyrene-
induced tumorigenesis in mouse tissues (Zheng et al.,
1992). Recently it was found that myristicin induces
cytotoxicity in human neuroblastoma SK-N-SH cells by
an apoptotic mechanism (Lee et al., 2005).
Citral, which is found in many essential oils and
comprises 70%–85% of lemongrass oil, is a novel
monoterpene inducer of glutathione-S-transferase class
π
, (GSTP1). This isozyme is responsible for the increase
in the total GST activity of the citral-treated rat
hepatocyte cells (Nakamura et al., 2003). Structure–
activity relationship studies revealed that trans-citral
(geranial) was the main contributor for the induction
of GSTP1. The aldehyde group conjugated with a trans-
double bond in trans-citral is an essential structural
factor for GST induction. On the other hand cis-citral
(neral) showed no activity. This suggested the explora-
tion of citral as a cancer chemopreventive agent
targeted towards inflammation-related carcinogenesis
such as skin cancer (Henderson et al., 1998) and colon
cancer (Mulder et al., 1995), both of which were found
to be due to lack of GSTP1 activity. The high content
of citral in lemongrass oil may explain the inhibitory
effect of that aromatic plant on the early phase of
hepatocarcinogenesis in rats (Puatanachokchai et al.,
2002). Citral also increased the hepatic glutathione-
S-transferase (GST) and aminopyrine demethylase
activities, and reduced glucuronyl transferase activity
(Vinitketkumnuen and Lertprasertsuk, 1997).
Although citral is generally recognized as safe for
human consumption as a food additive by the FDA
(GRAS), it is classified as a potential teratogen and
primary irritant (Abramovici and Rachmuth-Roizman,
1983). The National Toxicology Program (2003) con-
cluded that under the conditions of two-year feeding
studies there was no evidence of carcinogenic activity
of citral in male or female F344/N rats exposed to 1000,
2000 or 4000 ppm. There was no evidence of carcino-
genic activity of citral in male B6C3F1 mice exposed to
500, 1000 or 2000 ppm. There was, however, equivocal
evidence of carcinogenic activity in female B6C3F1
mice based on the increased incidence of malignant
lymphoma, thus the acceptable daily intake (ADI) of
citral has been proposed as 0–0.5 mg/kg/day (FAO/
WHO 2003).
Other essential oils elicit hepatoprotective activity
due to their phenolic and/or monoterpene content:
for example, black cumin (Nigella sativa), due to
thymoquinone (Mansour et al., 2001); orange essential
oil, due to d-limonene (Bodake et al., 2002); and sweet
fennel (Foeniculum vulgare) due to both d-limonene
and
β
-myrcene (Ozbek et al., 2003). In addition,
d-limonene exhibits chemopreventive efficacy in
preclinical hepatocellular carcinoma models (Parija and
Das, 2003; Guyton and Kensler, 2002; Jiri et al., 1999).
The mode of action originates, in part, from the induc-
tion of the specific cytochrome P450 isozymes includ-
ing CYP 2B1 and CYP2C (Maltzman et al., 1991).
d-Limonene is also a candidate for the chemoprevention
of skin cancer (Stratton et al., 2000), although it can
cause contact dermatitis, especially when oxidized.
Garlic essential oil is a rich source of volatile organo-
sulfur components (OSCs). These compounds are recog-
nized as a group of potential cancer chemopreventive
agents due to their activity for modulating phase I and
II drug detoxifying enzymes (Milner, 2001). The three
major OSCs of garlic essential oil, diallyl sulfide (DAS),
diallyl disulfide (DADS) and diallyl trisulfide (DATS),
were found differentially to mediate the transcriptional
levels of phase II detoxifying enzymes, NQO1 and HO1,
in human hepatoma (HepG2) cells (Chen et al., 2004).
DATS, with three sulfur atoms, was found to be the
most potent inducer of phase II enzyme gene expres-
sion, ARE activation and Nrf2 protein accumulation.
The effects of oral administration of garlic essential oil
and its three major OSCs on different phase I and phase
II hepatic detoxification enzymes in rat showed that
the essential oil and DAS significantly increased the
activity of the phase I enzyme (PROD) (Wu et al., 2002).
DADS and DATS significantly decreased the activity
of phase I enzyme (NDMAD). Garlic essential oil,
DADS, and DATS significantly increased the activity
of glutathione S-transferase, a phase II detoxifying
enzyme. The placental form of GST (GST
π
) level
was also increased by garlic oil and its three major
components. GST
π
is one of the GST isozymes which
are of special interest due to their relationship with
the development of human ovarian cancer (Hamada
et al., 1994) and colorectal cancer (Mulder et al., 1995).
The highest concentrations of DAS, DADS and DATS,
which are decomposition products of allicin, are found
in garlic essential oil extracted from crushed cloves using
steam or water distillation (Ibrel et al., 1990).
Cancer suppression
Essential oils and their individual aroma components
showed cancer suppressive activity when tested on a
number of human cancer cell lines including glioma,
colon cancer, gastric cancer, human liver tumor,
pulmonary tumors, breast cancer, leukemia and others.
Glioma is one of the most malignant human tumors
(De Angelis, 2001).
α
–Bisabolol, a major sesquiterpene alcohol in Chamo-
mile, (Matricaria chamomilla) essential oil, could be
considered as a promising inducer of apoptosis in highly
malignant glioma cells. It is neither toxic in animals nor
does it reduce the viability of normal astroglial cells
(Cavalieri et al., 2004). A significant effect on the treat-
ment of glioma was reported using the sesquiterpene
hydrocarbon elemene which is found in small amounts
in many essential oils: it prolonged quality survival time
of patients with glioma (Tan et al., 2000).
Geraniol, a monoterpene alcohol, elicited a dramatic
reduction in the amounts of thymidylate synthase (TS)
and thymidine kinase (TK) expression in colon cancer
cells (Carnesecchia et al., 2004). These two enzymes
are involved in 5-fluorouracil (5-FU) toxicity, in that a
decrease in these enzymes is related to enhanced 5-FU
cytotoxicity (Mans et al., 1999). Geraniol lowered the
resistance of cancer cells to 5-FU thus potentiating the
inhibition of tumor growth by the drug, and increasing
the survival time of nude mice grafted with the human
colorectal tumor cells TC118. Geraniol acts on at least
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 3
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
two different targets involved in the resistance of
cancer cells to 5-FU: it increases cell membrane
permeability leading to enhanced uptake of 5-FU by
colon cancer cells and causes a significant change in
the resting potential and cell membrane polarization,
which may trigger modifications of membrane bound
protein activity and alterations in intracellular signal-
ing pathways (Carnesecchi et al., 2002a, 2002b). A
major natural source of geraniol is Palmarosa oil
(Cymbopogon martini var martini), also known as East
Indian geranium, containing 59%–84% which is much
greater than most species of Geranium or Pelargonium
(Sirinivas, 1986).
d-Limonene showed antiangiogenic and proapoptotic
effects on human gastric cancer implanted in nude mice,
thus inhibiting tumor growth and metastasis (Guang
et al., 2004). d-Limonene can also induce the formation
of apoptotic bodies on BGC-823 gastric cancer cells in
a dose- and time-dependent manner (Guang et al., 2003)
and its efficacy was increased by combining it with
cytotoxic agents such as 5-fluorouracil. Administra-
tion of chow pellets containing 1% or 2% d-limonene
to male Sprague-Dawley rats resulted in significant
reductions in chemically induced, hepatocellular
carcinomas (Kaji et al., 2001). This effect could be re-
lated to its effect in inhibiting cell proliferation and
in enhancing apoptosis. d-Limonene also increased the
survival of lymphoma-bearing mice and modulated
the immune response, showing significant potential for
clinical application (Del Toro-Arreola et al., 2005). A
mechanism that may contribute to d-limonene efficacy
in the chemoprevention and/or therapy of chemically
induced human solid tumor cells has been proposed
(Chen et al., 1999; Jiri et al., 1999; Parija and Das, 2003).
Briefly, d-limonene can, in part, inhibit FPTase activ-
ity, inhibit the plasma-membrane associated P21ras
expression, and the post-translational isoprenylation
of P21ras. d-Limonene is found naturally in many
essential oils, especially citrus fruit peel where it con-
stitutes 90%–95% of the total oil. It is also found in
considerable amounts (26%–34%) in some spearmint
essential oils (Edris et al., 2003). The annual produc-
tion of d-limonene was estimated to be 50 000 tonnes
(Braddock and Cadwallader, 1995) which makes its price
as low as $1–2/kg (Mazzaro, 2000).
Diallyl trisulfide (DATS), a major constituent of
garlic essential oil, showed a high activity for arresting
the division of human liver tumor cells (J5) at the G2/
M phase of the cell cycle (Wu et al., 2004). The mecha-
nism of action probably involves regulating the protein
expressions of cyclin B1 and Cdk7. The chemother-
apeutic and chemopreventive activity of garlic essential
oil and its various organo-sulfur constituents against
different types of carcinogenesis have been reviewed
elsewhere (Thomson and Ali, 2003; Benjamin et al.,
1990).
It is accepted that aberrant angiogenesis is essential
for the progression of solid tumors and hematological
malignancies. Thus, antiangiogenic therapy is one of
the most promising approaches to control cancer.
Perillyl alcohol (POH) which is the hydroxylated ana-
logue of d-limonene, has the ability to interfere with
angiogenesis (Loutrari et al., 2004). POH either alone
or with PA (perillic acid, the major metabolite of POH
in the body), has a potential use as an anticancer drug
that stimulates different types of tumors to apoptosis,
inhibits their proliferation, or overcomes their resist-
ance to chemo-/radiotherapy (Yuri et al., 2004; Samaila
et al., 2004; Elegbede et al., 2003; Clark et al., 2003;
Rajesh et al., 2003; Rajesh and Howard 2003; Ahn
et al., 2003; Bardon et al., 2002; Burke et al., 2002;
Bardon et al., 1998). The antitumor activity of POH
emanates from its activity of modulating cellular pro-
cesses that control cell growth and differentiation (Azzoli
et al., 2003; Clark et al., 2002; Ariazi et al., 1999; Ren
and Gould, 1998; Gould, 1997 and Gould, 1995). Thus
POH, among other micronutrients, was investigated by
the National Cancer Institute (NCI) in NCI-sponsored
phase I, II, or III chemoprevention trials for prostate,
breast and colon cancers (Greenwald et al., 2002). How-
ever, it may not be an effective chemopreventive agent
for esophageal cancer in humans (Liston et al., 2003).
Unfortunately, despite evidence of anticancer activity
of POH in vitro, oral administration has not yet shown
any clinical antitumor activity (Bailey et al., 2004; Azzoli
et al., 2003; Liu et al., 2003; Meadows et al., 2002; Howard
et al., 2002). POH is found in small amounts in many
aromatic plants including lavender, peppermint, spear-
mint, perilla and lemongrass (Kelloff et al., 1996). Conyza
newii oil, (Compositae), contains 4.2% of perillyl alcohol
(Omolo et al., 2004) while Tetradenia riparia oil,
(Labiateae) contains 6.0% POH (Campbell et al., 1997).
POH can also be produced from d-limonene by micro-
bial biotransformation pathways (Duetz et al., 2003).
Eucalyptol (1,8-cineol) is found in high concentrations
(60%–90%) in the essential oil of eucalyptus (Eucalyp-
tus globulus) (Juergens et al., 1998) and 59% in car-
damom (Elettaria cardamomum, Zingbraceae) (Huang
et al., 1999). Treatment of human leukemia HL-60
cells with eucalyptol showed morphological changes,
(fragmentations of DNA) indicating an induction
of apoptosis (Moteki et al., 2002). However, this
effect was not shown in human stomach cancer KATO
III cells that received the same treatment with
eucalyptol.
In addition to the individual terpene components
mentioned above, several whole essential oils have
also shown anticancer activity in vitro. The essential
oil of lemon balm (Melissa officinalis L) was found
to be effective against a series of human cancer cell
lines (A549, MCF-7, Caco-2, HL-60, K562) and a
mouse cell line (B16F10) (De Sousa et al., 2004)
and that of Artemisia annua L. induced apoptosis
of cultured SMMC-7721 hepatocarcinoma cells (Li
et al., 2004). The essential oil of Australian tea tree
(Melaleuca alternifolia) and its major monoterpene
alcohol, terpinen-4-ol, were able to induce caspase-
dependent apoptosis in human melanoma M14 WT
cells and their drug-resistant counterparts, M14
adriamicin-resistant (Calcabrini et al., 2004). There
was evidence to suggest that the effect of the total oil
and of terpinen-4-ol was mediated by their interac-
tion with the plasma membrane and subsequent
reorganization of membrane lipids.
Hepatic arterial infusion with Curcuma oil had a
similar positive effect in treating primary liver cancer
as that of the chemical drugs (Cheng et al., 2001). The
essential oil of Tetraclinis articulate, (a conifer tree)
showed the hallmarks of apoptosis when tested on a
number of human cancer cell lines including melanoma,
breast and ovarian cancer in addition to peripheral
blood lymphocytes (Buhagiar et al., 1999).
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
4A. E. EDRIS
These results may draw the attention of cancer
researchers to further extend their clinical testing of
essential oils, and it would be interesting to investigate
the antitumor activity of a major individual terpene
constituent in comparison with its whole essential oil
source.
ESSENTIAL OILS AND CARDIOVASCULAR
DISEASES
Atherosclerosis
Atherosclerosis is a process in which deposits of plaque
build up in the innermost layer of the artery, the intima
(Barter, 2005). Plaque can eventually significantly re-
duce blood flow, leading to serious health problems.
Increased concentrations of oxidatively modified low
density lipoproteins (LDLs) in cholesterol play a
substantial role in disease initiation (Barter, 2005;
Valenzuela et al., 2004; Steinberg, 1997, Daugherty and
Roselaar, 1995). Atherosclerosis can therefore be slowed
down or inhibited by preventing the oxidation of LDLs
using a high daily intake of antioxidants.
Essential oils and their aroma volatile constituents
have shown an antioxidative activity against LDL
oxidation. Terpinolene, a monoterpene hydrocarbon,
can effectively inhibit the oxidation of both the lipid
part and the protein part of LDL. This inhibition is due
to a retarded oxidation of intrinsic carotenoids of LDL,
and not, as is the case with some flavonoids, to the
protection of intrinsic
α
-tocopherol (Grassmann et al.,
2003, 2005). Essential oils rich in phenolic constituents
such as eugenol and thymol have the highest anti-
oxidative activity against LDL oxidation (Naderi et al.,
2004) and these components can also change the
affinity of the LDL particles for the LDL receptor. A
relationship was found between the quantity and qual-
ity of phenolic components in the oil and its protection
against LDL oxidation: for instance, copper-catalysed
oxidation of human LDL in vitro is inhibited by 50%–
100% when eugenol is the major component of the
essential oil (as in clove oil), while inhibition was only
10%–50% for essential oils containing moderate
amounts of the phenolics, thymol, carvacrol or cuminol
(Teissedre and Waterhouse, 2000). In addition to the
phenolic constituents, the monoterpene hydrocarbon
γ
-
terpinene, was also found to inhibit LDL oxidation,
even in the propagation phase.
γ
-Terpinene generated
an antioxidative effect on the Cu2+-induced and AAPH-
induced oxidation of human LDL in vitro (Takahashi
et al., 2003). Tea tree essential oil is considered to be a
rich source of
γ
-terpinene (23.0%) (Brophy et al., 1989)
and
γ
-terpinene is also found in considerable amounts
in some citrus peel essential oils such as bergamot
(14%), mandarin (17%) and lemon (10%) (Mondello
et al., 1995). It has been recommended as an addition
to foods and beverages to protect against LDL oxida-
tion and to reduce plaque formation (Takahashi et al.,
2003).
Essential oils and some of their individual constitu-
ents can also lower total plasma cholesterol and
triglyceride levels which contribute to the formation of
plaque and consequently, atherosclerosis. Black cumin
oil (Nigella sativa Linn.) was found to decrease plasma
concentrations of cholesterol and triglycerides due to
the high content of thymoquinone (Ali and Blunden,
2003). The essential oil of Satureja khuzestanica,
an endemic plant of Iran, was reported to decrease
the normal blood lipid peroxidation level (Abdollahi
et al., 2003). Oral administration of dill seed essential
oil (Anethum graveolens) reduced triacylglyceride
levels by almost 42%, although total cholesterol
level was not reduced (Yazdanparast and Alavi, 2001).
α
-Curcumene, the major constituent (approx. 65%)
of the essential oil of Javanese turmeric (Curcuma
xanthorrhiza), exerts triglyceride-lowering activity on
serum as well as liver triglycerides (Yasni et al.,
1994).
Garlic essential oil significantly lowered serum
cholesterol and triglycerides while raising the level of
high-density lipoproteins in both healthy individuals
and patients with coronary heart disease (Bordia, 1981).
The hypolipidemic action of garlic oil is primarily due
to a decrease in hepatic cholesterogenesis (Mathew
et al., 1996). One of the consequences of atherosclerosis
is hypertension, and some essential oils exert hypoten-
sive activity when applied in vivo. Oral administration
of combinations of oregano, cinnamon, cumin, and other
essential oils decreased systolic blood pressure in rats
(Talpur et al., 2005) and intravenous administration of
the essential oil from the aerial parts of Mentha x villosa
induced a significant and dose-dependent hypotension
associated with decreases in heart rate (Guedes et al.,
2004). This activity was attributed to the volatile com-
ponent, piperitenone oxide, which represents 55.4% of
the oil. The hypotensive effect induced by the oil is
probably due to its direct cardiodepressant action and
peripheral vasodilation, which can be attributed to both
endothelium-dependent and endothelium-independent
mechanisms.
Intravenous administration of the essential oil of
basil (Ocimum gratissimum) induced an immediate
and significant hypotension and bradycardia (Lahlou
et al., 2004). The hypotensive activity of the essential
oil resulted from its vasodilator effects, acting directly
upon vascular smooth muscle. This effect was attrib-
uted, at least in part, to the actions of eugenol, which is
the major constituent of the oil. Clove bud essential oil
is the richest source of eugenol known (about 80%;
Deyama and Horiguchi, 1971) but from a safety point
of view, care must be taken in dealing with eugenol
due to its suspected carcinogenicity and hepatotoxicity
(National Toxicology Program, 1983).
Intravenous injection of the monoterpene alcohol
terpinen-4-ol decreased mean aortic blood pressure in
a dose-related manner, in conscious DOCA-salt hyper-
tensive rats (Lahlou et al., 2003). The mechanism of
action was related to the induction of vascular smooth
muscle relaxation rather than enhanced sympathetic
nervous system activity. Terpinene-4-ol is a major
constituent of several essential oils, particularly tea tree
(Brophy et al., 1989) and sweet marjoram essential oils
(Nykanen, 1986).
Essential oils and thrombosis
Thrombosis is usually associated with platelet activa-
tion and the release of eicosanoids which contribute to
initiation and aggravation of thrombosis. Prevention of
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 5
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
thrombogenesis has become one of the most important
targets for the prophylaxis and therapy of cardiocir-
culatory disorders with thromboembolic complications
(Fitzgerald, 2001). The antiplatelet agents currently
used for this purpose are effective in the prevention of
thromboembolic disease, but many have side effects
such as gastric erosion (e.g. aspirin), agranulocytosis
(e.g. ticlopidine), or show a poor separation between
therapeutic efficacy and hemorrhagic complications
(Van De Graaff and Steinhubl, 2001). For this reason,
plant extracts have been tested for their potential
antithrombotic activity. The essential oil of lavender,
(Lavandula hybrida Reverchon cv.), showed a broad
spectrum antiplatelet effect and was able to inhibit plate-
let aggregation induced by ADP, arachidonic acid,
collagen and the stable thromboxane receptor agonist
U46619 with no prohemorrhagic properties (Ballabenia
et al., 2004). Linalyl acetate (36% of lavender oil)
seemed to be the main active antiplatelet agent. Onion
(Allium cepa) is well known for promoting cardiovas-
cular health, and populations with a high consump-
tion of onions are associated with decreased rates of
atherosclerosis or thrombotic disease (Kendler, 1987).
This activity is due to inhibition of platelet aggrega-
tion and thromboxane formation by the organo-sulfur
components in the essential oil (Bordia et al., 1996;
Srivastava, 1986). The mechanism of the antiplatelet
effect of onion includes TXA2 synthase inhibition and
TXA2/PGH2 receptor blockade (Moon et al., 2000).
However, garlic was found to be more potent than onion
in lowering TXB2 levels (Bordia et al., 1996). Organo-
sulfur components such as allicin, isolated from garlic
essential oil, showed a potent inhibition of platelet
aggregation (Calvey et al., 1994; Lawson et al., 1992).
Allicin is formed from alliin when garlic cloves are
crushed or chewed and the enzyme alliinase is released
from the cell walls. However, ajoene has the highest
specific antithrombotic activity compared with any other
organo-sulfur compounds from garlic (Lawson et al.,
1992; Apitz-Castro et al., 1983). Ajoene is formed from
allicin during steam or water distillation of the essen-
tial oil from garlic cloves, or during storage in ethanol
(Block et al., 1986, Iberl et al., 1990). The presence
of vinyl groups attached by a disulfide bond makes
ajoene a highly reactive molecule which can inhibit
the release of both dense granules and
α
-granules
(Rendu et al., 1989). Ajoene can reduce platelet aggre-
gation induced by 0.1 U/mL thrombin by 94.7% after
a pre-stimulation incubation time for one minute at a
dose of 25 µM (Villar et al., 1997). The mechanism of
action of ajoene differs to that of other known inhibi-
tors of platelet aggregation. Ajoene penetrates the
membrane of intact platelets and reduces the viscosity
of the inner part of the lipid bilayer (Rendu et al., 1989),
thus interfering with the expression of the fibrinogen
receptor
α
IIB
β
3 at the cell surface, thereby inhibiting
fibrinogen binding (Apitz-Castro et al., 1986). Ajoene
also inhibits platelet aggregation through inhibiting the
formation of thromboxane A2 via altering arachidonic
acid metabolism. Moreover, it inhibits platelet aggre-
gation induced by adrenaline, collagen, adenosine
diphosphate and calcium ionophore A23187 (Srivastava
and Tyagi, 1993). Polysulfides, particularly dimethyl
trisulfide and diallyl trisulfide, found in both onion and
garlic oils also inhibit thromboxane synthesis in plate-
lets (Makheja and Bailey, 1990).
ESSENTIAL OILS AS ANTIBACTERIAL
AGENTS
The Ancient Egyptians used aromatic plants in
embalming to stop bacterial growth and prevent decay,
an effect attributed to a great extent to their essential
oils. Strong in vitro evidence indicates that essential
oils can act as antibacterial agents against a wide spec-
trum of pathogenic bacterial strains including Listeria
monocytogenes, L. innocua, Salmonella typhimurium,
Escherichia coli O157:H7, Shigella dysenteria, Bacillus
cereus, Staphylococcus aureus and Salmonella typhi-
murium (Schmidt et al., 2005; Jirovetz et al. 2005; Burt,
2004; Dadalioglu and Evrendilek, 2004; Nguefack
et al., 2004; Hulin et al., 1998) and many more (Deans
and Ritchie, 1987). Thyme and oregano essential oils
can inhibit some pathogenic bacterial strains such as
E. coli, Salmonella enteritidis, Salmonella choleraesuis
and Salmonella typhimurium (Penalver et al., 2005), with
the inhibition directly correlated to the phenolic com-
ponents carvacrol and thymol. The same correlation
was also confirmed for oils rich in carvacrol alone
(Santoyo et al., 2006). Eugenol and carvacrol showed
an inhibitory effect against the growth of four strains of
Escherichia coli O157:H7 and Listeria monocytogenes
(Gaysinsky et al., 2005). The presence of a phenolic
hydroxyl group, in carvacrol particularly, is credited with
its activity against pathogens such as Bacillus cereus
(Ultee et al., 1999; Ultee et al., 2002). Some essential
oils demonstrated antibacterial activity against zoonotic
enteropathogens including Salmonella spp., Escherichia
coli O157, Campylobacter jejunii and Clostridium
perfringens. Thus, these oils could possibly be used as
an alternative to antibiotics in animal feed (Wannissorn
et al., 2005).
Essential oils with high concentrations of thymol and
carvacrol e.g. oregano, savory and thyme, usually in-
hibit Gram-positive more than Gram-negative patho-
genic bacteria (Nevas et al., 2004). However the essential
oil of Achillea clavennae exhibited strong antibacterial
activity against the Gram ()-ve Haemophilus influenzae
and Pseudomonas aeruginosa respiratory pathogens,
while Gram (+)-ve Streptococcus pyogenes was the most
resistant to the oil (Skocibusic et al., 2004).
The major mode of infection transmission in hospital-
acquired infections is thought to be through hand
carrying of pathogens from staff to patient, and from
patient to patient (Boyce and Pittet, 2002; Naikoba
and Hayward, 2001), and a relationship between hand
hygiene and reduced transmission of infections been
reported (Reybrouck, 1986). Most antiseptic agents can
damage the skin, leading to a change in microbial flora,
and an increased shedding of the original protective
bacterial flora of the hand leads to an increased risk of
transmission of pathogenic microorganisms (Larson,
2001). Reports suggest that repeated use of formula-
tions containing tea tree essential oil (TTO) does not
lead to dermatological problems, nor affect the original
protective bacterial flora of the skin (Carson and Riley,
1995), so the antibacterial activity of some skin-wash
formulas containing TTO as well as pure TTO was
evaluated against Staphylococcus aureus, Acinetobacter
baumannii, Escherichia coli and Pseudomonas
aeruginosa (Messager et al., 2005a, 2005b). All formu-
lations showed antibacterial activity, but the efficacy of
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
6A. E. EDRIS
TTO appeared to be dependent on the formulation and
the concentration tested. The antibacterial activity of
tea tree essential oil has recently been reviewed (Carson
et al., 2006).
In the field of veterinary therapy, a cream formula-
tion containing 10% TTO caused significant and fast
relief against canine localized acute and chronic
dermatitis compared with commercial skin care
cream (Reichling et al., 2004). For the safe use of
tea tree essential oil as antibacterial agent for animals
or humans, the potential toxicity should be taken into
consideration (Carson et al., 2006; Hammer et al., 2005;
Carson and Riley, 1995).
The emergence of resistant pathogenic micro-
organisms in hospitals and in the community repre-
sents a problem for both the treatment of patients and
control of infection. Topical preparations containing
TTO can be considered in regimens for eradication
of methicillin-resistant Staphylococcus aureus in hos-
pitals (Dryden et al., 2004). The preparations were
found to be effective, safe and well tolerated. TTO
demonstrated a relatively short killing time (less than
60 min) for multidrug-resistant organisms, including
methicillin-resistant Staphylococcus aureus (MRSA),
glycopeptide-resistant Enterococci, aminoglycoside-
resistant Klebsiellae, Pseudomonas aeruginosa and
Stenotrophomonas maltophilia (May et al., 2000). MRSA
showed the highest resistance and longest time for eradi-
cation. It was concluded that the antimicrobial activity
of TTO is attributed to its high content of terpenen-4-ol.
Other multidrug-resistant pathogens such as
Pseudomonas aeruginosa and Escherichia coli can be
effectively inhibited by the essential oil of oregano
(Bozin et al., 2006).
Ocimum gratissimum essential oil can also inhibit
extracellular protease and the expression of O-lipopoly-
saccharide rhamnose in virulence and multidrug-resist-
ant strains of 22 Shigellae (Iwalokun et al., 2003). Thus,
the oil may find a use as a therapeutic measure against
shigellosis. Methicillin-resistant Staphylococcus aureus
can also be inhibited by the application of peppermint
and spearmint essential oils (Imai et al., 2001).Essen-
tial oils could be used as antibacterial agents against
some respiratory tract pathogens. The oil of Achillea
clavennae showed its maximum activity against Klebsiella
pneumoniae and penicillin-susceptible and penicillin-
resistant Streptococcus pneumoniae. The oil also exhib-
ited strong activity against Haemophilus influenzae and
Pseudomonas aeruginosa (Skocibusic et al., 2004).
An increased density of Helicobacter pylori in the
gastric mucosa is associated with severe gastritis and an
increased incidence of peptic ulcers (Kelly, 1998). The
activities of 60 essential oils against H. pylori P1 were
evaluated: 30 oils were able to affect the growth
in vitro, and 15 showed strong activity (Bergonzelli
et al., 2003). Among the individual constituents of these
oils, carvacrol, isoeugenol, nerol, citral and sabinene
exhibited the strongest anti-H. pylori effects. Further
investigations are underway regarding the ability of
essential oils to control H. pylori infections (McNulty
et al., 2001; Kalpoutzakis et al., 2001; Imai et al., 2001;
O’Gara et al., 2000).
Essential oils show bactericidal activity against
oral and dental pathogenic microorganisms and can
be incorporated into rinses or mouth washes for
pre-procedural infection control (Yengopal, 2004a),
general improvement of oral health (Yengopal, 2004b),
interdental hygiene (Yengopal, 2004c) and to control
oral malodor (Yengopal, 2004d). Croton cajucara Benth
essential oil was found to be toxic for some pathogenic
bacteria and fungi associated with oral cavity disease
(Alviano et al., 2005) and may be useful for controlling
the microbial population in patients with fixed ortho-
dontic appliances. A 6-month controlled clinical study
demonstrated that a mouthrinse containing essential oils
showed a comparable antiplaque and antigingivitis
activity to that containing the synthetic antibacterial
agent, chlorhexidine (Charles et al., 2004). Mouth rinses
containing essential oils (specially phenolic rich types)
with chlorhexidine gluconate are commonly used as
preprocedural preparations to prevent possible dis-
ease transmission, decrease chances of postoperative
infection, decrease oral bacterial load and decrease
aerosolization of bacteria (Hennessy and Joyce, 2004).
Mouth washes containing essential oils could also
be used as a part of plaque-control routine since they
can penetrate the plaque biofilm, kill pathogenic-
plaque-forming microorganisms by disrupting their cell
walls and inhibiting their enzymatic activity (Ouhayoun,
2003). In addition, essential oils in mouth washes pre-
vent bacterial aggregation, slow the multiplication and
extract bacterial endotoxins (Seymour, 2003).
The mechanisms by which essential oils can inhibit
microorganisms involve different modes of action, and
in part may be due to their hydrophobicity. As a result,
they get partitioned into the lipid bilayer of the cell
membrane, rendering it more permeable, leading to
leakage of vital cell contents (Burt, 2004; Juven et al.,
1994; Kim et al., 1995). Impairment of bacterial enzyme
systems may also be a potential mechanism of action
(Wendakoon and Sakaguchi, 1995).
ESSENTIAL OILS AS ANTIVIRAL AGENTS
Herpes simplex virus (type I, II) causes some of the
most common viral infections in humans, and can be
fatal. Synthetic antiviral drugs have been used to treat
Herpes infections (Fahad and Stepher, 1996; Wagstaff
et al., 1994), but not all are efficacious in treating
genital herpes infections. HSV-1 and HSV-2 have also
developed resistance to one of these (acyclovir) mainly
in immuno-compromised hosts (Birch et al., 1990;
Wagstaff et al., 1994). Plant extracts, especially essen-
tial oils, may afford a potential alternative to synthetic
antiviral drugs: they have demonstrated virucidal prop-
erties, with the advantage of low toxicity compared with
the synthetic antiviral drugs (Baqui et al., 2001; Primo
et al., 2001; Schnitzer et al., 2001). Incorporation of
Artemisia arborescens essential oil in multilamellar
liposomes greatly improved its activity against intra-
cellular Herpes simplex virus type-1 (HSV-1) (Sinicoa
et al., 2005). Melissa officinalis L. essential oil can
inhibit the replication of HSV-2, due to the presence
of citral and citronellal (Allahverdiyev et al., 2004)
and the ability to replicate of HSV-1 can be suppressed
by incubation with different essential oils in vitro. Of
these, lemongrass essential oil possessed the most potent
anti-HSV-1 activity and completely inhibited viral
replication after incubation for 24 h, even at a con-
centration of 0.1% (Minami et al., 2003). Peppermint
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 7
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
(Mentha piperita) essential oil exhibited high levels of
virucidal activity against HSV-1, HSV-2 and acyclovir-
resistant strain of HSV-1 in viral suspension tests
(Schuhmacher et al., 2003). The antiviral activity of the
oil was confirmed when the virus was pretreated with
the essential oil prior to adsorption. The essential oil
of Lippia junelliana and Lippia turbinate showed a
potent inhibition against Junin virus (Garcia et al., 2003).
Australian tea tree essential oil and to a lesser extent,
eucalyptus essential oil, demonstrated antiviral activity
against HSV-1,2 (Schnitzler et al., 2001). Both oils
affected the virus before or during adsorption, but not
after penetration into the host cell. The essential oil of
Santolina insularis showed an antiviral activity in toto
against HSV-1 and HSV-2 in vitro and was capable
of preventing cell-to-cell virus spread in infected cells
(De Logu et al., 2000). The oil directly inactivated virus
particles, thus preventing adsorption of virion to host
cells. Isoborneol, a common monoterpene alcohol,
showed dual virucidal activity against HSV-1 (Armaka
et al., 1999) and specifically inhibited glycosylation
of viral polypeptides. Unfortunately, no literature was
found concerning the antiviral applications of essential
oils against epidemic viruses such as HIV or hepatitis C
viruses, but the promising results illustrated here may
promote further investigations in this area.
ESSENTIAL OILS AS ANTIOXIDANTS
Free radicals and other reactive oxygen species cause
oxidation of biomolecules including proteins, amino
acids, unsaturated lipids and DNA, and ultimately
produce molecular alterations related to aging, arterio-
sclerosis and cancer (Gardner, 1997), Alzheimer’s
disease (Butterfield and Lauderback, 2002), Parkinson’s
disease, diabetes and asthma (Zarkovic, 2003). The
human body is equipped with an inherent defense
system which can quench free radicals present in
almost all cells (Halliwell and Gutteridge, 1990). An
imbalance between free radical production and their
removal by the body’s antioxidant system leads to
a phenomena known as ‘oxidative stress’ (Abdollahi
et al., 2004; McCord, 2000). In this situation, an exter-
nal supply of antioxidants is necessary to regain a
balance between free radicals and antioxidants.
Essential oils, as natural sources of phenolic com-
ponents, attract investigators to evaluate their activity
as antioxidants or free radical scavengers. The essential
oils of basil, cinnamon, clove, nutmeg, oregano and
thyme have proven radical-scavenging and antioxidant
properties in the DPPH radical assay at room tempera-
ture (Tomaino et al., 2005). The order of effectiveness
was found to be: clove >> cinnamon > nutmeg > basil
oregano >> thyme. The essential oil of Thymus serpyllus
showed a free radical scavenging activity close to that
of the synthetic butylated hydroxytoluene (BHT) in a
β
-carotene/linoleic acid system (Tepe et al., 2005). The
antioxidant activity was attributed to the high content
of the phenolics thymol and carvacrol (20.5% and
58.1%, respectively). Thymus spathulifolius essential oil
also possessed an antioxidant activity due to the high
thymol and carvacrol content (36.5%, 29.8%, respec-
tively; Sokmen et al., 2004). The antioxidant activity of
oregano (Origanum vulgare L., ssp. hirtum) essential
oil was comparable to that of
α
-tocopherol and BHT,
but less effective than ascorbic acid (Kulisic et al., 2004).
The activity is again attributed to the content of thymol
and carvacrol (35.0%, 32.0%, respectively). Although
dietary supplementation of oregano oil to rabbits
delayed lipid oxidation, this effect was less than that
of supplementation with the same concentration of
α
-
tocopheryl acetate (Botsoglou et al., 2004). However,
when tested on turkeys it showed an equivalent per-
formance to the same concentration of
α
-tocopheryl
acetate in delaying iron-induced, lipid oxidation
(Papageorgiou et al., 2003).
The essential oils of Salvia cryptantha and Salvia
multicaulis have the capacity to scavenge free radicals.
The activity of these oils was higher than that of curcu-
min, ascorbic acid or BHT (Tepe et al., 2004). The
essential oil of Achillea millefolium subsp. millefolium
(Asteraceae) exhibited a hydroxyl radical scavenging
effect in the Fe3+–EDTA–H2O2 deoxyribose system
and inhibited the non-enzymatic lipid peroxidation of
rat liver homogenate (Candan et al., 2003). In addition,
Curcuma zedoaria essential oil was found to be an
excellent scavenger for DPPH radical (Mau et al., 2003).
The antioxidant activity of essential oils cannot be
attributed only to the presence of phenolic constitu-
ents; monoterpene alcohols, ketones, aldehydes, hydro-
carbons and ethers also contribute to the free radical
scavenging activity of some essential oils. For instance,
the essential oil of Thymus caespititius, Thymus
camphoratus and Thymus mastichina showed antioxi-
dant activity which in some cases was equal to that of
α
-tocopherol (Miguel et al., 2004). Surprisingly, the three
species are characterized by high contents of linalool
and 1,8-cineole, while thymol or carvacrol are almost
absent. The essential oil of lemon balm (Melissa
officinalis L.) shows an antioxidant and free radical
scavenging activity (Mimica-Dukic et al., 2004) with the
most powerful scavenging constituents comprising neral/
geranial, citronellal, isomenthone and menthone. Tea
tree (Melaleuca alternifolia) oil has been suggested as
a natural antioxidant alternative for BHT (Kim et al.,
2004) with the inherent antioxidant activity attributed
mainly to the
α
-terpinene,
γ
-terpinene and
α
-terpinolene
content. Essential oils isolated from Mentha aquatica
L., Mentha longifolia L. and Mentha piperita L., were
able to reduce DPPH radicals into the neutral DPPH-
H form (Mimica-Dukic et al., 2003). The most powerful
scavenging constituents was found to be 1,8-cineole for
the oil of M. aquatica while menthone and isomenthone
were the active principles of M. longifolia and M.
piperita.
It is clear that essential oils may be considered as
potential natural antioxidants and could perhaps be
formulated as a part of daily supplements or additives
to prevent oxidative stress that contributes to many
degenerative diseases.
ESSENTIAL OILS AS ANTIDIABETIC AGENTS
Diabetes is a disease in which the body does not pro-
duce or properly use insulin.
Investigators have conducted few studies exploring
the potential benefits of essential oils as hypoglycemic
agents and publications on the subject are scarce. Some
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
8A. E. EDRIS
essential oils may aggravate diabetes: for instance,
rosemary essential oil showed hyperglycemic and
insulin release inhibitory effects in diabetic rabbits
(Al-Hader et al., 1994). Broadhurst et al. (2000) have
emphasized that the lipophilic fraction of aromatic
plants (i.e. essential oils) are not generally responsible
for any antidiabetic activity showed by these plants,
but Talpur et al. (2005) indicated that an oral adminis-
tration of a combination of essential oils including
cinnamon, cumin, fennel, oregano, myrtle besides
others, was able to enhance insulin sensitivity in type
2 diabetes, in addition to lowering circulating glucose
in the tolerance testing in rats. The essential oil of
Satureja khuzestanica resulted in significant decreases
in fasting blood glucose level in diabetic rats (Abdollahi
et al., 2003). More research is needed to confirm the
veracity of the hypoglycemic activity of other essential
oils and to elucidate their mechanism of action.
ESSENTIAL OILS AS SKIN PENETRATION
ENHANCERS FOR TRANSDERMAL DRUG
DELIVERY
The oral and nasal routes are the most common non-
invasive paths for drug administration but are not
suitable for some drugs, either due to stomach acidity
or hepatic first-pass metabolism (Balfour and McTavish,
1992; Corson, 1993). Nasal delivery is often charac-
terized by poor absorption of lipophilic drugs (Orive
et al., 2003). Thus, the skin can present a promising
route for administration of drugs in a non-invasive way.
This phenomena is called topical or transdermal drug
delivery. The principle barrier to topical drug delivery
is the stratum corneum (SC) which is the outer most
layer of the skin. The permeability of the SC can be
increased by using skin penetration enhancers (Barry,
1991). Detailed reviews describing synthetic enhancers
are available (Williams and Barry, 2004; Ghafourian
et al., 2004).
Essential oils and their terpene constituents may
be acceptable natural alternatives to synthetic skin
penetration enhancers. They are characterized by their
relatively low price and promising penetration enhanc-
ing activities. The mechanism of skin penetration
enhancing activity of terpenes was postulated (Vaddi
et al., 2002; Higaki et al., 2003; Cornwell and Barry,
1994; Barry, 1991; Cornwell and Barry, 1991; Williams
and Barry, 1991; Williams and Barry, 1989). Due to
the popularity of these essential oils, their toxicities are
well documented (Opdyke, 1974–1976), and found to
be relatively low compared with most synthetic pen-
etration enhancers. The evaluation of the sensitization,
carcinogenicity and toxicity of these oils and their indi-
vidual terpene constituents are continuously carried
out by organizations such as the Research Institute for
Fragrance Materials (RIFM), International Flavor and
Fragrance Association (IFRA), Flavor Essence Manu-
facturers Association (FEMA) and the National Toxi-
cology Program (NTP).
Terpenes such as menthol and cineole were employed
as natural enhancers to improve the skin penetration
of propranolol, a
β
-blocker, which has a short biolo-
gical half-life and is subjected to extensive hepatic
first-pass metabolism (Amnuaikit et al., 2005). Cineole
and menthol are reported to improve the skin per-
meation of hydrophilic drugs better than other ter-
penes (Narishetty and Panchagnula, 2004). Menthol and
limonene produced maximum permeation of melatonin
along with traditional enhancers including fatty alcohols
and fatty acids (Kanikkannan et al., 2004). On the other
hand, menthol and menthone failed to enhance the
penetration of high-molecular-weight, lipophilic drugs
such as paclitaxel (Panchagnula et al., 2004). The
combination of two penetration enhancers of different
classes such as terpenes (e.g. cineole) and fatty acids
(e.g. oleic acid), synergistically enhanced transdermal
flux of zidovudine in addition to reducing lag time. On
the other hand, combinations of menthol with oleic or
linolenic acid did not enhance transdermal delivery
(Thomas and Panchagnula, 2003). The proper choice
of the terpene enhancer is dictated by the lipophilicity
or hydrophicity of the drug (El-Kattan et al., 2001).
Some essential oils themselves have been investigated
as potential skin penetration enhancers. Basil essential
oil showed an enhancing activity for accelerating
transdermal delivery of indomethacin (Fang et al., 2004).
The mechanism of action is probably due to the in-
creased skin–vehicle partitioning by the oils. Niaouli
essential oil showed a high activity for the permeation
of estradiol through hairless mouse skin in vitro (Monti
et al., 2002). In addition, eucalyptus and chenopodium
essential oils caused a near 30-fold increase in the
5-fluorouracil permeability coefficient (Williams and
Barry, 1989).
ESSENTIAL OILS, AROMATHERAPY AND
MASSAGE THERAPY
The word ‘aromatherapy’ combines two words: aroma
(a fragrance or swee smell) and therapy (a treatment).
Aroma and massage therapy are the practice of using
essential oils for psychological and physical well-being
via inhalation or massage.
The term ‘aromatherapy’ may be confusing to non-
specialists because it is used to describe a wide range of
practices involving odorous substances. Thus, massage
therapy, even when using essential oils, cannot be con-
sidered as aromatherapy. Only aroma delivery through
inhalation, to induce psychological or physical effects,
can be defined as aromatherapy (Buchbauer and
Jirovetz, 1993, 1994). Nevertheless, the clinical use of
essential oils and their volatile constituents via inhala-
tion or massage has expanded worldwide.
Inhalation
Inhalation of essential oils or their individual volatile
terpenes has a significant role in controlling the central
nervous system. For instance, aroma inhalation of Storax
pill essential oil and preinhalation of Acorus gramineus
rhizome essential oil are used in Chinese folk medicine
in the treatment of epilepsy (Koo et al., 2004; Koo
et al., 2003). The oils showed an inhibitory effect on the
central nervous system via the gamma-aminobutyric acid
(GABA)-ergic neuromodulation system. This effect
originates from the enhancement of GABA levels in
the brain (Koo et al., 2003). The fragrance compounds,
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 9
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
cis-jasmone and methyl jasmonate, which characterize
the aroma of Jasminum grandiflorum have a tranquil-
lizing effect on the brain upon inhalation (Hossain
et al., 2004). They significantly increased the sleeping
time of mice induced by pentobarbital. This indicates
that these fragrant compounds were absorbed by the
brain and thereby potentiated the GABA receptor
response. Cedrol, which is a major component of
cedarwood essential oil, showed a sedative effect and
prolonged pentobarbital-induced sleeping time in rats
upon inhalation (Kagawa et al., 2003). The vapor of
lavender essential oil or one of its main components,
linalool, may contribute to relieving tension when
inhaled. They may also be applicable to the treatment
of menopausal disorders via inhalation (Yamada et al.,
2005). Lavender (Lavandula hybrida Reverchon
‘Grosso’) essential oil demonstrated an interesting
analgesic activity, mainly relevant after inhalation, at
doses devoid of sedative side effects (Barocelli et al.,
2004). In the field of complementary and alternative
respiratory medicine, inhalation of peppermint essen-
tial oil vapors has been suggested as an adjunct in com-
bined multidrug therapy in patients with disseminated
and infiltrative pulmonary tuberculosis. The action of
the oil is mainly due to the antimicrobial activity of its
volatile constituents (Shkurupii et al., 2002). Cinnamon
and clove oils also showed an inhibition to different
Gram (+)-ve and Gram ()-ve pathogenic bacteria from
the vapor phase (Lopez et al., 2005). Aroma inhalation
of lavender, peppermint, rosemary and clary-sage
essential oils can significantly decrease symptoms asso-
ciated with anxiety and stress. Inhalation of essential
oils can also modulate sympathetic activity in normal
adults: for example, the inhalation of pepper, estragon,
fennel or grapefruit essential oils resulted in 1.5- to
2.5-fold increase in relative sympathetic activity. In
contrast, fragrance inhalation of rose oil or patchouli
oil caused a 40% decrease in relative sympathetic
activity. On a hormonal level, inhalation of pepper oil
induced a 1.7-fold increase in plasma adrenaline con-
centration compared with the resting state, while inha-
lation of rose oil caused a 30% decrease in adrenaline
concentration (Haze et al., 2002). The rise in rat plasma
adrenocorticotrophic hormone caused by stress was sig-
nificantly reduced by inhalation of chamomile essential
oil (Yamada et al., 1996). The same effect can be
achieved by the intraperitoneal injection of diazepam,
a synthetic tranquillizer. The mode of action of Chamo-
mile essential oil is at least in part via benzodiazepine-
sensitive receptors, probably GABA. Other essential
oils also have sedative properties upon inhalation
(Buchbauer et al., 1992, 1993).
Inhalation of the volatile fractions of lavender and
monarda essential oils (0.1–0.2 mg/m3 air) reduced the
cholesterol content in the aorta and also atherosclerotic
plaques (Nikolaevskii et al., 1990), but had no effect on
the content of cholesterol in the blood.
Massage
Inflammatory diseases, such as allergy, rheumatism and
arthritis are often alleviated using essential oil massage
therapy (Maruyama et al., 2005; Lawless, 1997). Aller-
gic symptoms can be suppressed by tea tree oil (Brand
et al., 2002a; Koh et al., 2002), lavender oil (Kim and
Cho, 1999) and the volatile constituent, terpenene-4-ol
(Hart et al., 2000). This action is mainly due to the
suppression of histamine release (Brand et al., 2002b)
and cytokine production (Brand et al., 2001). Cutane-
ous delivery of geranium essential oil using massage
can suppress the inflammatory symptoms with neutrophil
accumulation and edema (Maruyama et al., 2005). A
lavender fragranced cleansing gel had a significant
transient effect of improving mood and making people
feel more relaxed (Field et al., 2005). Aromatic materi-
als, topically applied, showed positive effects on lung
mucus clearance in patients with chronic airway ob-
struction (Hasani et al., 2003). Even foot soaking in
warm water containing lavender essential oil followed
by reflexology treatment with jojoba oil containing
lavender, appeared to be effective for alleviating
fatigue in terminally ill cancer patients (Kohara et al.,
2004). Massage therapy using essential oil can be useful
in the treatment for people suffering from dementia.
The term ‘dementia’ is used to describe the symptoms
that occur when the brain is affected by specific dis-
eases and conditions, including Alzheimer’s disease,
stroke and other rarer conditions. Symptoms of demen-
tia include loss of memory, confusion and problems
with speech and understanding. Preliminary reports
have indicated positive effects of massage therapy
using selected essential oils for managing behavioral
and psychological symptoms in dementia. The essential
oil of Melissa officinalis (lemon balm) applied cutane-
ously in a lotion to patients with severe dementia was
found to be an effective treatment (Ballard et al., 2002).
The potential efficiency of massage therapy with essen-
tial oils to decrease agitation in patients suffering
dementia raise the question of whether inhalation of
the essential oil or its cutaneous delivery through
massage is responsible for the alleviative effect. Snow
et al. (2004) indicated that inhalation of lavender essen-
tial oil did not decrease agitation in severely demented
patients and a similar result had previously been re-
ported by Holmes et al. (2002). Cutaneous application
of the essential oil through massage may therefore be
necessary to achieve the alleviative effect in patients
with dementia.
Care should be taken when dealing with essential
oils in massage. Some essential oils have the potential
to be toxic (Prashar et al., 2004; Hayes and Markovic,
2003), while others initiate allergic reactions when
applied to the skin via massage (Veien et al., 2004;
Schnuch et al., 2004; Crawford et al., 2004; Maddocks-
Jennings, 2004; Scardamaglia et al., 2003; Mozelsio
et al., 2003; Bleasel et al., 2002; Vilaplana and
Romaguera, 2002; Romaguera and Vilaplana, 2000).
These allergic reactions arise from certain constituents,
e.g. benzyl alcohol, cinnamyl alcohol, eugenol, iso-
eugenol, hydroxycitronellal, geraniol and many others
(European Parliament, 2002). For this reason, warn-
ings must be printed on the label of essential oils
containing these components, and aromatherapy
practitioners and massage therapists should be also
aware of the potential for these adverse effects – and
be equipped to deal with them if they should arise
(Maddocks-Jennings and Wilkinson, 2004). At the same
time, physicians and other health professionals should
be able to differentiate between aesthetic applications
of odors and clinical uses of essential oils in order to
advise and better inform patients.
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
10 A. E. EDRIS
CONCLUSIONS
This review attempts to shed light on the therapeutic
potential of essential oils and their aroma volatile con-
stituents in the prevention or therapy of disease. The
results reviewed in this article are aimed at attracting
the attention of researchers seeking new drugs from
natural products as well as those investigating the phar-
maceutical diversity of essential oils. The data presented
provide a basis for reviving the old art of ‘essential
oil therapy’ based on our modern scientific knowledge
of their mode of action, supported by safety issues
described here. Thus essential oils and their constitu-
ents can hopefully be considered in the future for more
clinical evaluations and possible applications, and as
adjuvants to current medications.
Acknowledgement
The author is indebted to Professor Gary Reineccius at the Food
Science and Nutrition Department, The University of Minnesota, for
his constructive opinions, his helpful notes and his support in English
language edition of this review.
REFERENCES
Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaie A. 2004.
Pesticides and oxidative stress: a review.
Med Sci Monit
10:
RA 141–147.
Abdollahi M, Salehnia A, Mortazavi S
et al.
2003. Antioxidant,
antidiabetic, antihyperlipidemic, reproduction stimulatory
properties and safety of essential oil of
Satureja Khuzes-
tanica
in rat
in vivo
: a toxicopharmacological study.
Med
Sci Monit
9: 331–335.
Abramovici A, Rachmuth-Roizman P. 1983. Molecular structure–
teratogenicity relationships of some fragrance additives.
Toxicology
29: 143–156.
Ahmad H, Tijerina M, Tobola A. 1997. Preferential over-
expression of a class MU glutathione S-transferase subunit
in mouse liver by myristicin.
Biochem Biophys Res Commun
236: 825– 828.
Ahn K, Lee C, Choi E, Griffin R, Song C, Park J. 2003. Cytotoxicity
of perillyl alcohol against cancer cells is potentiated by
hyperthermia.
Int J Radiat Oncol Biol Phys
57: 813– 819.
Ali B, Blunden G. 2003. Pharmacological and toxicological
properties of
Nigella sativa
.
Phytother Res
17: 299– 305.
Allahverdiyev A, Duran N, Ozguven M, Koltas S. 2004. Antiviral
activity of the volatile oils of
Melissa officinalis
L. against
Herpes simplex virus type-2.
Phytomedicine
11: 657–661.
Al-Hader A, Hasan, Z, Agel M. 1994. Hyperglycemic and
insulin release inhibitory effects of
Rosmarinus officinalis.
J. Ethnopharmacol
43(3): 217–221.
Alviano W, Mendonca-Filho R, Alviano D
et al.
2005. Antimicro-
bial activity of
Croton cajucara
Benth linalool-rich essential
oil on artificial biofilms and planktonic microorganisms.
Oral
Microbiol Immunol
20: 101–105.
Amnuaikit C, Ikeuch I, Ogawara K, Higaki K, Kimura T. 2005.
Skin permeation of propranolol from polymeric film
containing terpene enhancers for transdermal use.
Int J
Pharmacol
289: 167–178.
Apitz-Castro R, Cabrera S, Cruz M, Ledezma E, Jain M. 1983.
Effects of garlic extract and of three pure components
isolated from it on human platelet aggregation, arachidonate
metabolism, release reaction and platelet ultrastructure.
Thromb Res
32: 155–169.
Apitz-Castro R, Ledezma E, Escalante J, Jain M. 1986. The
molecular basis of the antiplatelet action of ajoene: direct
interaction with the fibrinogene receptor.
Biochem Biophys
Res Commun
141: 145–150.
Ariazi E, Satomi Y, Ellis M
et al.
1999. Activation of the trans-
forming growth factor ß signaling pathway and induction
of cytostasis and apoptosis in mammary carcinomas treated
with the anticancer agent perillyl alcohol.
Cancer Res
59:
1917–1928.
Armaka M, Papanikolaou E, Sivropoulou A, Arsenakis M.
1999. Antiviral properties of isoborneol, a potent inhibitor
of herpes simplex virus type-1.
Antiviral Res
43: 79–92.
Azzoli C, Miller V, Ngm K
et al.
2003. A phase I trial of perillyl
alcohol in patients with advanced solid tumors.
Cancer
Chemother Pharmacol
51: 493–498.
Bailey H, Wilding G, Tutsch K
et al.
2004. A phase I trial of
perillyl alcohol administered four times daily for 14 days
out of 28 days.
Cancer Chemother Pharmacol
54: 368 –376.
Balfour J, McTavish D. 1992. Transdermal estradiol. A review
of its pharmacological profile, and therapeutic potential in
the prevention of postmenopausal osteoporosis.
Drugs
Aging
2: 487–507.
Ballabenia V, Tognolinia M, Chiavarinia M
et al.
2004. Novel
antiplatelet and antithrombotic activities of essential oil from
Lavandula hybrida
Reverchon ‘grosso’.
Phytomedicine
11:
596– 601.
Ballard C, O’Brien J, Reichelt K, Perry E. 2002. Aromatherapy
as a safe and effective treatment for the management of
agitation in severe dementia: the results of a double-blind,
placebo-controlled trial with
Melissa
.
J Clin Psychiatry
63:
553– 558. Comment in
J Clin Psychiatry
2003; 64: 732;
author reply 732.
Baqui A, Kelley J, Jabra-Rizk M, Depaola L, Falkler W, Meiller
T. 2001.
In vitro
effects of oral antiseptics human
immunodeficiency virus-1 and herpes simplex virus type 1.
J Clin Periodontol
28: 610– 616.
Bardon S, Foussard V, Fournel S, Loubat A. 2002. Monoterpenes
inhibit proliferation of human colon cancer cells by
modulating cell cycle-related protein expression.
Cancer Lett
181: 187–194.
Bardon S, Picard K, Martel P. 1998. Monoterpenes inhibit cell
growth, cell cycle progression, and cyclin D1 gene expres-
sion in human breast cancer cell lines.
Nutr Cancer
32: 1–
7.
Barocelli E, Calcina F, Chiavarini M
et al.
2004. Antinociceptive
and gastroprotective effects of inhaled and orally adminis-
tered
Lavandula hybrida
Reverchon ‘Grosso’ essential oil.
Life Sci
76: 213–223.
Barry B. 1991. Lipid-protein-partitioning theory of skin penetra-
tion enhancement.
J Control Rel
15: 237–248.
Barter P. 2005. The inflammation: Lipoprotein cycle.
Athero-
sclerosis Suppl
6(2): 15–20.
Benjamin H, Lau M, Padma P, Tadi M, Jeffrey M. 1990.
Allium
sativum
(garlic) and cancer prevention.
Nutr Res
10: 937–
948.
Bergonzelli G, Donnicola D, Porta N, Corthésy-Theulaz I. 2003.
Essential oils as components of a diet-based approach to
management of
Helicobacter
infection.
Antimicrob Agents
Chemother
47: 3240– 3246.
Birch C, Tachedjian G, Doherty R, Hayes K, Gust, I. 1990. Altered
sensitivity to antiviral drugs of herpes simplex virus isolates
from a patient with the acquired immunodeficiency syn-
drome.
J Infect Dis
162: 731–734.
Bleasel N, Tate B, Rademaker M. 2002. Allergic contact
dermatitis following exposure to essential oils.
Australas J
Dermatol
43: 211–213.
Block E, Ahmad S, Catalfamo J, Jain M, Apitz-Castro R. 1986.
Antithrombotic organosulfur compounds from garlic: struc-
tural, mechanistic and synthetic studies.
J Am Chem Soc
108: 7045–7055.
Bodake H, Panicker K, Kailaje V, Rao V. 2002. Chemopreventive
effect of orange oil on the development of hepatic
preneoplastic lesions induced by N-nitrosodiethylamine in
rats: an ultrastructural study.
Indian J Exp Biol
40: 245–251.
Bordia A. 1981. Effect of garlic on blood lipids in patients with
coronary heart disease.
Am J Clin Nutr
34: 2100–2103.
Bordia T, Mohammed N, Thomson M, Ali M. 1996. An evalu-
ation of garlic and onion as antithrombotic agents.
Prostaglandins Leuko Essent Fatty Acids
54: 183–186.
Botsoglou N, Florou-Paneri P, Christaki E, Giannenas I, Spais A.
2004. Performance of rabbits and oxidative stability of
muscle tissues as affected by dietary supplementation with
oregano essential oil.
Arch Anim Nutr
58: 209–218.
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 11
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
Boyce J, Pittet D. 2002. Guideline for hand hygiene in health-
care settings: recommendations of the Healthcare Infection
Control Practices Advisory Committee and the HICPAC/
SHEA/APIC/IDSA Hand Hygiene Task Force.
Infect Control
Hosp Epidemiol
23(S12): S3– S40.
Bozin B, Mimica-Dukic N, Simin N, Anackov G. 2006. Charac-
terization of the volatile composition of essential oils of
some Lamiaceae spices and the antimicrobial and antioxi-
dant activities of the entire oils.
J Agric Food Chem
54:
1822–1828.
Braddock R, Cadwallader K. 1995. Bioconversion of citrus
d
-
limonene.
Fruit Flavors
596: 142–148.
Brand C, Ferrante A, Prager R
et al.
2001. The water-soluble
components of the essential oil of
Melaleuca alternifolia
(tea tree oil) suppress the production of superoxide by
human monocytes, but not neutrophils, activated
in vitro
.
Inflamm Res
50: 213–219.
Brand C, Grimbaldeston M, Gamble J, Finlay-Jones J, Hart P.
2002a. Tea tree oil reduces the swelling associated with the
different phase of a contact hypersensitivity response.
Inflamm Res
51: 236 –244.
Brand C, Townley S, Finlay-Jones J, Hart P. 2002b. Tea tree oil
reduces histamine-induced oedema in murine ears.
Inflamm
Res
51: 283–289.
Broadhurst C, Polansky M, Anderson R. 2000. Insulin-like bio-
logical activity of culinary and medicinal plant aqueous
extract
in vitro
.
J Agric Food Chem
48: 849– 852.
Brophy J, Davis N, Southwell I, Stiff I, Williams L. 1989. Gas
chromatographic quality control for oil of
Melaleuca
terpinene-4-ol type (Australian tea tree).
J Agric Food Chem
37: 1330–1335.
Buchbauer G, Jager W, Jirovetz L, Meyer F, Dietrich H. 1992.
Effects of valerian root oil, borneol, isoborneol, bornyl
acetate and isobornyl acetate on the motility of laboratory
animals (mice) after inhalation.
Pharmazie
47: 620– 622.
Buchbauer G, Jirovetz L. 1993. Aromatherapie-Definition und
discussion uber den stand der forschung (German).
Arstezeitschrift fur Naturheilverfahren
34: 259–264.
Buchbauer G, Jirovetz L. 1994. Aromatherapy use of fragrance
and essential oils as medicament.
Flavour Fragr J
9: 217–
222.
Buchbauer G, Jirovetz L, Jager W, Plank C, Dietrich H. 1993.
Fragrance compounds and essential oils with sedative
effects upon inhalation.
J Pharm Sci
82: 660– 664.
Buhagiar J, Podesta M, Wilson A, Micallef M, Ali S. 1999. The
induction of apoptosis in human melanoma, breast and
ovarian cancer cell lines using an essential oil extract from
the conifer
Tetraclinis articulate.
Anticancer Res
19: 5435–
5443.
Burke Y, Ayoubi A, Werner S
et al.
2002. Effects of the isopren-
oids perillyl alcohol and farnesol on apoptosis biomarkers
in pancreatic cancer chemoprevention.
Anticancer Res
22:
3127–3134.
Burt S. 2004. Essential oils: their antibacterial properties
and potential applications in foods – a review.
Int J Food
Microbiol
94: 223–253.
Butterfield D, Lauderback C. 2002. Lipid peroxidation and
protein oxidation in Alzheimer’s disease brain: potential
causes and consequences involving amyloid beta-peptide-
associated free radical oxidative stress.
Free Radic Biol Med
32: 1050–1060.
Calcabrini A, Stringaro A, Toccacieli L
et al.
2004. Terpinen-4-
ol, the main component of
Melaleuca alternifolia
(tea tree)
oil inhibits the
in vitro
growth of human melanoma cells.
J
Invest Dermatol
122: 349–360.
Calvey E, Roach J, Block E. 1994. Supercritical fluid chromato-
graphy of garlic (
Allium sativum
) extracts with mass
spectrometric identification of allicin.
J Chromatogr Sci
32:
93– 96.
Campbell W, Gammon D, Smith P, Abrahams M, Purves T.
1997. Composition and antimalarial activities
in vitro
of the
essential oil of
Tetradenia riparia. Planta Med
63: 270– 272.
Candan F, Unlu M, Tepe B
et al.
2003. Antioxidant and antimi-
crobial activity of the essential oil and methanol extracts of
Achillea millefolium
subsp.
millefolium
Afan. (Asteraceae).
J Ethnopharmacol
87: 215–220.
Carnesecchi S, Bradaia A, Fischer B
et al.
2002a. Perturbation
by geraniol of cell membrane permeability and signal
transduction pathways in human colon cancer cells.
J
Pharmacol Exp Ther
303: 711–715.
Carnesecchia S, Bras-Gonc R, Bradaiac A
et al.
2004. Geraniol,
a component of plant essential oils, modulates DNA
synthesis and potentiates 5-fluorouracil efficacy on human
colon tumor xenografts.
Cancer Lett
215: 53– 59.
Carnesecchi S, Langley K, Exinger F, Gosse F, Raul F. 2002b.
Geraniol, a component of plant essential oils, sensitizes
human colonic cancer cell to 5-fluorouracil treatment.
J
Pharmacol Exp Ther
301: 625– 630.
Carson F, Hammer A, Riley V. 2006.
Melaleuca alternifolia
(Tea
Tree) oil: a review of antimicrobial and other medicinal
properties.
Clin Microbiol Rev
19: 50– 62.
Carson C, Riley T. 1995. Toxicity of the essential oil of
Melaleuca
alternifolia
or tea tree oil.
J Toxicol Clin Toxicol
33: 193–
195.
Cavalieri E, Mariotto S, Fabrizi C
et
al.
2004.
a
-Bisabolol, a nontoxic
natural compound, strongly induces apoptosis in glioma
cells.
Biochem Biophys Res Commun
315: 589– 594.
Charles C, Mostler K, Bartels L, Mankodi S. 2004. Comparative
antiplaque and antigingivitis effectiveness of a chlorhexidine
and an essential oil mouthrinse: 6-month clinical trial.
J
Clin Periodontol
31: 878– 884.
Chen C, Pung D, Leong V
et al.
2004. Induction of detoxifying
enzymes by garlic organosulfur compounds through tran-
scription factor NRF2: effect of chemical structure and stress
signals.
Free Radic Biol Med
37: 1578–1590.
Chen X, Yano Y, Hasuma T, Yoshimata T, Yinna W, Otani S.
1999. Inhibition of farnesyl protein transferase and P21ras
membrane association by d-limonene in human pancreas
tumor cells
in vitro
.
Chin Med Sci J
14: 138–144.
Cheng J, Chang G, Wu W. 2001. A controlled clinical study
between hepatic arterial infusion with embolized
Curcuma
aromatic oil and chemical drugs in treating primary liver
cancer.
Zhongguo Zhong Xi Yi Jie He Za Zhi
(
Chin J Integr
Trad Western Med
) 21: 165–167. Abstract is in English and
available on www.pubmed.org
Clark S, Perman S, Sahin M, Jenkins G, Elegbede J. 2002.
Antileukemia activity of perillyl alcohol (POH): uncoupl-
ing apoptosis from G0/G1 arrest suggests that the primary
effect of POH on Bcr/Abl-transformed cells is to induce
growth arrest.
Leukemia
16: 213–222.
Clark S, Zhong L, Filiault D
et al.
2003. Anti-leukemia effect of
perillyl alcohol in Bcr/Abl-transformed cells indirectly inhib-
its signaling through Mek in a Ras- and Raf-independent
fashion.
Clin Cancer Res
9: 4494– 4504.
Cornwell A, Barry W. 1991. The effects of a series of homo-
logous terpene alcohols on the lipid structure of human
stratum corneum as assessed by differential scanning
calorimetry. In
Prediction of Percutaneous Penetration
,
Scott
RC, Guy H, Hadgraft J, Bodde E (eds), Vol. 2. IBC Technical
Services: London, 394– 400.
Cornwell A, Barry W. 1994. Sesquiterpene components of
volatile oils as skin penetration enhancers for the hydrophilic
permeant 5-fluorouracil.
J Pharm Pharmacol
46: 261–269.
Corson S. 1993. Clinical experience with Systen, a new trans-
dermal form of hormone replacement therapy.
Int J Fertil
Menopausal Stud
38 (Suppl. 1): 36– 44.
Crawford G, Sciacca J, James W. 2004. Tea tree oil: cutaneous
effects of the extracted oil of
Melaleuca alternifolia.
Derma-
titis
15: 59– 66.
Dadalioglu I, Evrendilek G. 2004. Chemical compositions and
antibacterial effects of essential oils of Turkish oregano
(
Origanum minutiflorum
), bay laurel (
Laurus nobilis
), Span-
ish lavender (
Lavandula stoechas
L.), and fennel (
Foeniculum
vulgare
) on common foodborne pathogens.
J Agric Food
Chem
52: 8255– 8260.
Daugherty A, Roselaar S. 1995. Lipoprotein oxidation as a
mediator of atherogenesis: insights from pharmacological
studies.
Cardiovasc Res
29: 297–231.
Deans S, Ritchie G. 1987. Antibacterial properties of plant
essential oils.
Int J Food Microbiol
5:
165–180.
De Angelis L. 2001. Brain tumors.
N Engl J Med
344: 114
123.
De Logu A, Loy G, Pellerano M, Bonsignore L, Schivo M. 2000.
Inactivation of HSV-1 and HSV-2 and prevention of cell-
to-cell virus spread by
Santolina insularis
essential oil.
Antiviral Res
48: 177–185.
Del Toro-Arreola S, Flores-Torales E, Torres-Lozano C
et al.
2005. Effect of D-limonene on immune response in BALB/c
mice with lymphoma.
Int Immunopharmacol
5: 829– 838.
De Sousa A, Alviano D, Blank A, Alves P, Alviano C, Gattass C.
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
12 A. E. EDRIS
2004.
Melissa officinalis
L. essential oil: antitumoral and
antioxidant activities.
J Pharm Pharmacol
56: 677–681.
Deyama T, Horiguchi T. 1971. Studies on the components of
essential oil of clove (
Eugenia caryophylatta Thumberg
).
Yakugaku Zasshi
91: 1383–1386. (English abstract is avail-
able on www.pubmed.org)
Dryden M, Dailly S, Crouch M. 2004. A randomized, controlled
trial of tea tree topical preparations versus a standard
topical regimen for the clearance of MRSA colonization.
J
Hosp Infect
58: 86–87.
Duetz W, Bouwmeester H, van Beilent J, Witholt B. 2003.
Biotransformation of limonene by bacteria, fungi, yeast and
plants.
Appl Microbiol Biotechnol
61: 269–277.
Edris A, Shalaby A, Fadel H. 2003. Evaluation of a chemotype
of spearmint (
Mentha spicata
L.) growing in Siwa Oasis,
Egypt.
Eur Food Technol
218: 74 –78.
Elegbede J, Flores R, Wang C. 2003. Perillyl alcohol and
perillaldehyde induced cell cycle arrest and cell death in
BroTo and A549 cells cultured
in vitro
.
Life Sci
73: 2831–
2840.
El-Kattan A, Asbill C, Kim N, Michniak B. 2001. The effects of
terpene enhancers on the percutaneous permeation of drugs
with different lipophilicities.
Int J Pharm
215: 229–240.
Elson C. 1995. Suppression of mevalonate pathway activities
by dietary isoprenoids: protective roles in cancer and car-
diovascular disease.
J Nutr
125: 1666S–1672S.
European Parliament. 2002. New 7th Amendment to Annex III –
Part 1, (Directive 76/768/EEC).
Fahad A, Stepher L. 1996. New anti-herpes virus agents. Their
targets and therapeutics.
Potent Drugs
52: 17–32.
Fang J, Leu Y, Hwang T, Cheng H. 2004. Essential oils from
Sweet Basil (
Ocimum basilicum
) as novel enhancers to
accelerate transdermal drug delivery.
Biol Pharm Bull
27:
1819–1825.
FAO/ WHO. 2003.
Summary of Evaluations Performed by the
Joint FAO/WHO
Expert Committee on Food Additives
.
International Program on Chemical Safety (IPCS) INCHEM.
web site: http://www.inchem.org/documents/jecfa/jeceval/
jec_384.htm
Field T, Diego M, Hernandez-Reif M
et al.
2005. Lavender
fragrance cleansing gel effects on relaxation.
Int J Neurosci
115: 207–222.
Fitzgerald D 2001. Vascular biology of thrombosis. The role of
platelet–vessel wall adhesion.
Neurology
57: S1–S4.
Garcia C, Talarico L, Almeida N, Colombres S, Duschatzky C,
Damonte B. 2003. Virucidal activity of essential oils from
aromatic plants of San Luis, Argentina.
Phytother Res
17:
1073–1075.
Gardner P. 1997. Superoxide-driven aconitase FE-S center
cycling.
Biosci Rep
17: 33–/42.
Gaysinsky S, Davidson P, Bruce D, Weiss J. 2005. Growth
inhibition of
Escherichia coli
O157:H7 and
Listeria mono-
cytogenes
by carvacrol and eugenol encapsulated in sur-
factant micelles.
J Food Prot
68: 2559–2566.
Ghafourian T, Zandasrar P, Hamishekar H, Nokhodchi A. 2004.
The effect of penetration enhancers on drug delivery through
skin: a QSAR study.
J Cont Release
99: 113–125.
Gould M. 1995. Prevention and therapy of mammary cancer
by monoterpenes.
J Cell Biochem
Suppl 22: 139–144.
Gould M. 1997. Cancer chemoprevention and therapy by
monoterpenes.
Environ Health Perspect
105 (Suppl 4): 977–
979.
Grassmann J, Hippeli S, Spitzenberger R, Elstner F. 2005. The
monoterpene terpinolene from the oil of
Pinus mugo
L.
in concert with
α
-tocopherol and beta-carotene effectively
prevents oxidation of LDL.
Phytomedicine
12: 416– 423.
Grassmann J, Hippeli S, Vollmann R, Elstner E. 2003. Anti-
oxidative properties of the essential oil from
Pinus mugo
.
J
Agric Food Chem
51: 7576–7582.
Greenwald P, Milner J, Anderson D, McDonald S. 2002.
Micronutrients in cancer chemoprevention.
Cancer Meta-
stasis Rev
21: 217–230.
Guang L, Feng B, Zhan L, Yu Z. 2003. D-limonene induces
apoptosis of gastric cancer cells.
Zhonghua Zhong Liu Za
Zhi
(
Chin J Oncol
) 25: 325–727 (the abstract is in English
and available on www.pubmed.org
Guang L, Li-Bin Z, Bing-An F, Ming-Yang Q, Li-Hua Y, Ji-Hong
X. 2004. Inhibition of growth and metastasis of human
gastric cancer implanted in nude mice by d-limonene.
World
J Gastroenterol
10: 2140–2144.
Guedes D, Silva D, Barbosa-Filho J, de Medeiros I. 2004.
Endothelium-dependent hypotensive and vasorelaxant
effects of the essential oil from aerial parts of
Mentha x
villosa
in rats.
Phytomedicine
1: 490–497.
Guenther E. 1950. In
The Essential Oil
vol. IV. D.Van Nostrand:
New York.
Guyton K, Kensler T. 2002. Prevention of liver cancer.
Curr Oncol
Rep
4: 464– 470.
Halliwell B, Gutteridge J. 1990. The antioxidants of human
extracellular fluids.
Arch Biochem Biophys
280: 1–8.
Hamada S, Kamada M, Furumoto H, Hirao T, Aono T. 1994.
Expression of glutathione S-transferase-pi in human
ovarian cancer as an indicator of resistance to chemo-
therapy.
Gynecol Oncol
52: 313– 319.
Hammer A, Carson F, Riley V, Nielsen B. 2006. A review of the
toxicity of
Melaleuca alternifolia
(tea tree) oil.
Food Chem
Toxicol
44(5): 616 625.
Harman D. 1995. Role of antioxidant nutrients in ageing:
overview.
Age
18: 51–62.
Hart P, Brand C, Carson C, Riley T, Prager R, Finlay-Jones J.
2000. Terpinen-4-ol the main component of the essential
oil of
Melaleuca alternifolia
(tea tree oil), suppresses
inflammatory mediator production by activated human
monocytes.
Inflamm Res
49: 619– 626.
Hasani A, Pavia D, Toms N, Dilworth P, Agnew E. 2003. Effect
of aromatics on lung mucociliary clearance in patients with
chronic airways obstruction.
J Altern Complement Med
9:
243– 249.
Hayes A, Markovic B. 2003. Toxicity of Australian essential oil
Backhousia citriodora
(lemon myrtle). Part 2. Absorption
and histopathology following application to human skin.
Food Chem Toxicol
41: 1409–1416.
Haze S, Sakai K, Gozu Y. 2002. Effects of fragrance inhalation
on sympathetic activity in normal adults.
Jpn J Pharmacol
90: 247–253.
Henderson C, Smith A, Ure J, Brown K, Bacon E, Wolf C. 1998.
Increased skin tumorigenesis in mice lacking
π
-class glutathi-
one S-transferase.
Proc Natl Acad Sci USA
95: 5275–5280.
Hennessy B, Joyce A. 2004. A survey of preprocedural anti-
septic mouth rinse use in Army dental clinics.
Mil Med
169:
600– 603.
Higaki K, Amnuaikit C, Kimura T. 2003. Strategies for overcom-
ing the stratum corneum: chemical and physical approaches.
Am J Drug Deliv
1: 187–214.
Holmes C, Hopkins V, Hensford C, MacLaughlin V, Wilkinson
D, Rosenvinge H. 2002. Lavender oil as a treatment for
agitated behaviour in severe dementia: a placebo control-
led study.
Int J Geriat Psychiatry
17: 305– 308.
Hossain S, Aoshima H, Koda H, Kiso Y. 2004. Fragrances in
oolong tea that enhance the response of GABAA receptors.
Biosci Biotechnol Biochem
68: 1842–1848.
Howard B, Donna L, Harris S
et al.
2002. A phase II trial of daily
perillyl alcohol in patients with advanced ovarian cancer.
Eastern Cooperative Oncology Group Study E2E96.
Gynecol
Oncol
85: 464– 468.
Huang Y, Fang J, Hung C, Wu P, Tsai Y. 1999. Cyclic
monoterpene extract from cardamom oil as a skin permea-
tion enhancer for indomethacin:
in vitro
and
in vivo
stud-
ies.
Biol Pharm Bull
22: 642– 646.
Hulin V, Mathot A, Mafart P. 1998. Les propriétés anti-
microbiennes des huiles essentielles et composés d’arômes.
Sci Aliments
18: 563–582.
Ibrel B, Winkler G, Knobloch K. 1990. Products of allicin trans-
formation: Ajoene and dithiins. Characterization and their
determination by HPLC.
Planta Med
56: 202–211.
Imai H, Osawa K, Uasuda H, Hamashima H, Arai T, Sasatsu M.
2001. Inhibition by the essential oils of peppermint and
spearmint of the growth of pathogenic bacteria.
Microbios
106(S1): 31–39.
Iwalokun B, Gbenle G, Adewole T, Smith S, Akinsinde K,
Omonigbehin E. 2003. Effects of
Ocimum gratissimum
L.
essential oil at subinhibitory concentrations on virulent and
multidrug-resistant
Shigella
strains from Lagos, Nigeria.
APMIS
111: 477–482.
Jiri R, Parija T, Das B. 1999. d-Limonene chemoprevention of
hepatocarcinogenesis in AKR mice: inhibition of c-jun and
c-myc.
Oncol Rep
6: 1123–1127.
Jirovetz L, Buchbauer G, Denkova Z
et al.
2005. Antimicrobial
testings and gas chromatographic analysis of pure oxygen-
ated monoterpenes 1,8-cineol,
α
-terpineol, terpene-4-ol and
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 13
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
camphor as well as target compounds in essential oils of
pine (
Pinus pinaster
), rosemary (
Rosmarinus officinalis
) and
tee tree (
Melaleuca alternifolia
).
Sci Pharm
73: 27–39.
Juergens U, Stober M, Vetter H. 1998. Inhibition of cytokine
production and arachidonic acid metabolism by eucalyptol
(1,8-cineole) in human blood monocytes
in vitro
.
Eur J Med
Res
3: 508– 510.
Juven J, Kanner J, Schved F, Weisslowicz H. 1994. Factors that
interact with antimicrobial action of thyme essential oil and
its active constituents.
J Appl Bacteriol
76: 626– 631.
Kagawa D, Jokura H, Ochiai R, Tokimitsu I, Tsubone H. 2003.
The sedative effects and mechanism of action of cedrol
inhalation with behavioral pharmacological evaluation.
Planta Med
69: 637–641.
Kaji I, Tatsuta M, Iishi H, Baba M, Inoue A, Kasugai H. 2001.
Inhibition by d-limonene of experimental hepatocarcino-
genesis in Sprague-Dawley rats does not involve p21(ras)
plasma membrane association.
Int J Cancer
93: 441–
444.
Kalpoutzakis E, Aligiannis N, Mentis A, Mitaku S, Charvala
C. 2001. Composition of the essential oil of two nepeta
species and
in vitro
evaluation of their activity against
Helicobacter pylori
.
Planta Med
67: 880– 883.
Kanikkannan N, Andega S, Burton S, Babu R, Singh M. 2004.
Formulation and
in vitro
evaluation of transdermal patches
of melatonin.
Drug Dev Ind Pharm
30: 205–212.
Kelloff GJ, Boone CW, Crowell J
et al.
1996. New agents for
cancer chemoprevention.
J Cell Biochem Suppl
26: 1–28.
Kelly D. 1998. The physiology and metabolism of the human
gastric pathogen
Helicobacter pylori
.
Adv Microb Physiol
40: 137–189.
Kendler B. 1987. Garlic (
Allium sativum
) and onion (
Allium cepa
):
a review of their relationship to cardiovascular disease.
Prevent Med
16: 670–685.
Kim H, Chen F, Wu C, Wang X, Chung H, Jin Z. 2004. Evalua-
tion of antioxidant activity of Australian tea tree (
Melaleuca
alternifolia
) oil and its components.
J Agric Food Chem
52:
2849–2854.
Kim H, Cho S. 1999. Lavender oil inhibits immediate-type
allergic reaction in mice and rats.
J Pharm Pharmacol
51:
221–226.
Kim J, Marshall M, Wei C. 1995 Antimicrobial activity of
some essential oils components against five foodborne
pathogens.
J Agric Food Chem
43: 2839–2845.
Koh K, Pearce A, Marshma, G, Finlay-Jones J, Hart P. 2002.
Tea tree oil reduces histamine-induced skin inflammation.
Br J Dermatol
147: 1212–1217.
Kohara H, Miyauchi T, Suehiro Y, Ueoka H, Takeyama H, Morita
T. 2004. Combined modality treatment of aromatherapy,
footsoak, and reflexology relieves fatigue in patients with
cancer.
J Palliat Med
7: 791–796.
Koo B, Lee S, Ha J, Lee D. 2004. Inhibitory effects of the essen-
tial oil from SuHeXiang Wan on the central nervous system
after inhalation.
Biol Pharm Bull
27: 515–519.
Koo B, Park K, Ha J, Park J, Lim J, Lee D. 2003. Inhibitory
effects of the fragrance inhalation of essential oil from
Acorus gramineus
on central nervous system.
Biol Pharm
Bull
26: 978–982.
Kulisic T, Radonic A, Katalinic V, Milos M. 2004. Analytical,
nutritional and clinical methods use of different methods
for testing antioxidative activity of oregano essential oil.
Food Chem
85: 633–640.
Lahlou S, Interaminense F, Leal-Cardoso J, Morais S, Duarte G.
2004. Cardiovascular effects of the essential oil of
Ocimum
gratissimum
leaves in rats: role of the autonomic nervous
system.
Clin Exp Pharmacol Physiol
1: 219–225.
Lahlou S, Leal-Cardoso J, Duarte G. 2003 Antihypertensive
effects of the essential oil of
Alpinia zerumbet
and its main
constituent, terpinen-4-ol, in DOCA-salt hypertensive
conscious rats.
Fundam Clin Pharmacol
17: 323– 330.
Larson E. 2001. Hygiene of the skin: when is clean too clean?
Emerg Infect Dis
7: 225–230.
Lawless J. 1997.
The Complete Illustrated Guide to Aromath-
erapy
. Element Books: Dorset.
Lawson L, Ransom D, Hughes B. 1992. Inhibition whole blood
platelet aggregation by compounds in garlic clove extract
and commercial garlic products.
Thromb Res
65: 141–156.
Lee B, Kim J, Jung J
et al.
2005. Myristicin-induced neurotoxicity
in human neuroblastoma SK-N-SH cells.
Toxicol Lett
157:
49– 56.
Li Y, Li M, Wang L, Jiang Z, Li W, Li H. 2004. Induction of
apoptosis of cultured hepatocarcinoma cell by essential
oil of
Artemisia Annul
L.
Sichuan Da Xue Xue Bao Yi Xue
Ban
(
J West China Univ Med Sci
) 35: 337–339. Abstract is
in English and available on www.pubmed.org
Liston B, Nines R, Carlton P
et al.
2003. Perillyl alcohol as
a chemopreventive agent in N-nitrosomethylbenzylamine-
induced rat esophageal tumorigenesis.
Cancer Res
63: 2399–
2403.
Liu G, Oettel K, Bailey H
et al.
2003. Phase II trial of perillyl
alcohol (NSC 641066) administered daily in patients with
metastatic androgen independent prostate cancer.
Invest
New Drugs
21: 367–372.
Lopez P, Sanchez C, Batlle R, Nerin C. 2005. Solid- and vapor-
phase antimicrobial activities of six essential oils: suscepti-
bility of selected foodborne bacterial and fungal strains.
J
Agric Food Chem
53: 6939– 6946.
Loutrari H, Hatziapostolou M, Skouridou V
et al.
2004. Perillyl
alcohol is an angiogenesis inhibitor.
J Pharmacol Exp Ther
311: 568– 575.
Maddocks-Jennings W. 2004. Critical incident: idiosyncratic
allergic reactions to essential oils.
Complement Ther Nurs
Midwifery
10: 58–60.
Maddocks-Jennings W, Wilkinson J. 2004. Aromatherapy prac-
tice in nursing: literature review.
J Adv Nurs
48: 93 –103.
Makheja A, Bailey J. 1990. Antiplatelet constituents of garlic
and onion.
Agents Actions
29: 360–364.
Maltzman H, Christou M, Gould M, Jefcoate C. 1991. Effects
of monoterpenoids on
in vivo
DMBA-DNA adduct forma-
tion and on phase I hepatic metabolizing enzymes.
Carcinogenesis
12: 2081–2090.
Mans D, Grivicich I, Peters G, Schwartsmann G. 1999. Sequence-
dependent growth inhibition and DNA damage formation
by the irinotecan-5-fluorouracil combination in human
colon carcinoma cell lines.
Eur J Cancer
35: 1851–1861.
Mansour M, Ginawi O, El-Hadiyah T, El-Khatib A, Al-Shabanah
O, Al-Sawaf H. 2001. Effects of volatile oil constituents of
Nigella sativa
on carbon tetrachloride-induced hepatotoxicity
in mice: evidence for antioxidant effects of thymoquinone.
Res Commun Mol Pathol Pharmacol
110: 239–251.
Maruyama N, Sekimoto Y, Ishibashi H
et al.
2005. Suppression
of neutrophil accumulation in mice by cutaneous applica-
tion of geranium essential oil.
J Inflamm
2: 1–11.
Mathew B, Daniel R, Augusti K. 1996. Hypolipidemic effect
of garlic protein substituted for casein in diet of rats
compared to those of garlic oil.
Indian J Exp Biol
34: 337–
340.
Mau J, Laib E, Wang N, Chen C, Chang C, Chyau C. 2003.
Composition and antioxidant activity of the essential oil
from
Curcuma zedoaria
.
Food Chem
82: 583– 591.
May J, Chan C, King A, Williams L, French G. 2000. Time-kill
studies of tea tree oils on clinical isolates.
J Antimicrob
Chemother
45: 639– 643.
Mazzaro D. 2000. Orange oil,
d
-limonene market unsettled due
to Brazilian delay.
Chem Marketing Rep
258: 18 –22.
McCord J. 2000. The evolution of free radicals and oxidative
stress.
Am J Med
108: 652–659.
McDonald J, Marchand M, Langer R. 2004. Improving upon the
in vitro
biological activity of antithrombotic disulfides.
Blood
Coagulation Fibrinolysis
15: 447–450.
McNulty C, Wilson M, Havinga W, Johnston B, O’Gara E Maslin
D. 2001. A pilot study to determine the effectiveness of
garlic oil capsules in the treatment of dyspeptic patients
with
Helicobacter pylori
.
Helicobacter
6: 249–253.
Meadows S, Mulkerin D, Berlin J
et al.
2002. Phase II trial of
perillyl alcohol in patients with metastatic colorectal can-
cer.
Int J Gastrointest Cancer
32: 125–128.
Mehta M, Tome W, Olivera G. 2000. Radiotherapy for brain
tumors.
Curr Oncol Rep
2: 438–444.
Messager S, Hammer K, Carson C, Riley T. 2005a. Assessment
of the antibacterial activity of tea tree oil using the Euro-
pean EN 1276 and EN 12054 standard suspension tests.
J
Hosp Infect
59: 113–125.
Messager S, Hammer K, Carson C, Riley T. 2005b. Effectiveness
of hand-cleansing formulations containing tea tree oil
assessed
ex vivo
on human skin and
in vivo
with volun-
teers using European standard EN 1499.
J Hosp Infect
59:
220–228.
Miguel G, Simones M, Figueiredo A, Barroso J, Pedro L,
Carvalho L. 2004. Composition and antioxidant activities of
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
14 A. E. EDRIS
the essential oils of
Thymus caespititius
,
Thymus camphor-
atus
and
Thymus mastichina
.
Food Chem
86: 183–188.
Milner JA. 2001. A historical perspective on garlic and cancer
.
J Nutr
131: 1027S–1031S.
Mimica-Dukic N, Bozin B, Sokovic M, Mihajlovic B, Matavulj M.
2003. Antimicrobial and antioxidant activities of three
Mentha
species essential oils.
Planta Med
69: 413– 419.
Mimica-Dukic N, Bozin B, Sokovic M, Simin N. 2004. Antimicro-
bial and antioxidant activities of
Melissa officinalis
L.
(Lamiaceae) essential oil.
J Agric Food Chem
52: 2485–
2489.
Minami M, Kita M, Nakaya T, Yamamoto T, Kuriyama H, Imanishi
J. 2003. The inhibitory effect of essential oils on herpes
simplex virus type-1 replication
in vitro
.
Microbiol Immunol
47: 681–684.
Mondello L, Dugo P, Bartle D. 1995 Automated HPLC-HRGC:
A powerful method for essential oil analysis. Part V. Identi-
fication of terpene hydrocarbons of bergamot, lemon,
mandarin, sweet orange, bitter orange, grapefruit, Clemen-
tine and Mexican lime oils by coupled HPLC-HRGC-MS (ITD).
Flavour Fragr J
10: 33– 42.
Monti D, Chetoni P, Burgalassi S, Najarro M, Fabrizio M, Boldrini
E. 2002. Effect of different terpene-containing essential oils
on permeation of estradiol through hairless mouse skin.
Int
J Pharm
237: 209–214.
Moon C, Jung Y, Kim M, Lee S, Baik E, Park S. 2000. Mecha-
nism for antiplatelet effect of
Allium cepa
in rat and human
platelet.
Prostaglandins Leukot Essent Fatty Acids
62: 277–
283.
Morita T, Jinno K, Kawagishi H
et al.
2003. Hepatoprotective
effect of myristicin from nutmeg (
Myristica fragrans
)
on lipopolysaccharide/d-galactosamine-induced liver injury.
J Agric Food Chem
51: 1560–1565.
Morse M, Stoner G. 1993. Cancer chemoprevention: principle
and prospects.
Carcinogenesis
14: 1737–1746.
Moteki H, Hibasami H, Yamada Y, Katsuzaki H, Imai K, Komiya
T. 2002. Specific induction of apoptosis by 1,8-cineole in
two human leukemia cell lines, but not a in human stom-
ach cancer cell line.
Oncol Rep
9: 757–760.
Mozelsio N, Harris K, McGrath K, Grammer L. 2003. Immediate
systemic hypersensitivity reaction associated with topical
application of Australian tea tree oil.
Allergy Asthma Proc
24: 73 –75.
Mulder T, Verspaget H, Sier C
et al.
1995. Glutathione S-
transferase-pi in colorectal tumors is predictive for overall
survival.
Cancer Res
55: 2696–2702.
Naderi G, Asgary S, Ani M, Sarraf-Zadegan N, Safari M. 2004.
Effect of some volatile oils on the affinity of intact and
oxidized low-density lipoproteins for adrenal cell surface
receptors.
Mol Cell Biochem
267: 59– 66.
Naikoba S, Hayward A. 2001. Effectiveness of interventions
aimed at increasing handwashing in healthcare workers – a
systematic review.
J Hosp Infect
47: 173–180.
Nakamura Y, Miyamoto M, Murakami A, Ohigashi H, Osawa T,
Uchida K. 2003. A phase II detoxification enzyme inducer
from lemongrass: identification of citral and involvement of
electrophilic reaction in the enzyme induction.
Biochem
Biophys Res Commun
302: 593–600.
Narishetty S, Panchagnula R. 2004. Transdermal delivery
of zidovudine: effect of terpenes and their mechanism of
action.
J Control Rel
95: 367–379.
National Toxicology Program (1983) Carcinogenesis Studies
of Eugenol (CAS No. 97-53-0) in F344/N Rats and B6C3F1
Mice (Feed Studies). Technical report 223. Web site: http://
ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr223.pdf and http://
ntp.niehs.nih.gov/index.cfm?objectid=0706392B-FC21-9098-
2E10402B9BAC8AF1
National Toxicology Program. 2003. NTP technical report (505)
on the toxicology and carcinogenesis studies of citral
(microencapsulated) (CAS NO. 5392-40-5), in F344/N RATS
and B6C3F1 mice (feed studies). http://ntp.niehs.nih.gov/ntp/
htdocs/LT_rpts/tr505.pdf
Nevas M, Korhonen A, Lindstrom M, Turkki P, Korkeala H. 2004.
Antibacterial efficiency of Finnish spice essential oils against
pathogenic and spoilage bacteria.
J Food Prot
67: 199–202.
Nguefack J, Budde B, Jakobsen M. 2004. Five essential oils
from aromatic plants of Cameroon: their antibacterial activ-
ity and ability to permeabilize the cytoplasmic membrane
of
Listeria innocua
examined by flow cytometry.
Lett Appl
Microbiol
39: 395–400.
Nikolaevskii V, Kononova N, Pertsovskii A, Shinkarchuk I. 1990.
Effect of essential oils on the course of experimental
atherosclerosis.
Patol Fiziol Eksp Te
5: 52–53 (Article in
Russian, abstract in English available on www.pubmed.org).
Nykanen I. 1986. High resolution gas chromatographic-mass
spectrometric determination of the flavor composition of
marjoram (
Origanum mariorama L.
) cultivated in Finland.
Z
Lebensm Unters Forsch
182: 267–272.
O’Gara E, Hill D, Maslin D. 2000. Activities of garlic oil, garlic
powder, and their diallyl constituents against
Helicobacter
pylori
.
Appl Environ Microbiol
66: 2269–2273.
Omolo M, Okinyo D, Ndiege I, Lwande W, Hassanali A. 2004.
Repellency of essential oils of some Kenyan plants against
Anopheles gambiae. Phytochemistry
65: 2797–2802.
Opdyke DJ. 1974 –1976. Monographs on fragrance raw materi-
als.
Food Cosmet Toxicol
12–14 Supplements.
Orive G, Hernandez R, Gascon A, Dominguez-Gil A, Pedraz J.
2003. Drug delivery in biotechnology: present and future.
Current Opin Biotech
14: 659–664.
Ouhayoun JP. 2003. Penetrating the plaque biofilm: impact of
essential oil mouthwash.
J Clin Periodontol
30(S5): 10–12.
Ozbek H, Ugras S, Dulger H
et al.
2003. Hepatoprotective effect
of
Foeniculum vulgare
essential oil.
Fitoterapia
74: 317–
319.
Panchagnula R, Desu H, Jain A, Khandavilli S. 2004. Effect of
lipid bilayer alteration on transdermal delivery of a high-
molecular-weight and lipophilic drug: studies with paclitaxel.
J Pharm Sci
93: 2177–2183.
Papageorgiou G, Botsoglou N, Govaris A, Giannenas I, Iliadis
S, Botsoglou E. 2003. Effect of dietary oregano oil and
alpha-tocopheryl acetate supplementation on iron-induced
lipid oxidation of turkey breast, thigh, liver and heart tis-
sues.
J Anim Physiol Anim Nutr (Berl)
87: 324– 335.
Parija T, Das B. 2003. Involvement of YY1 and its correlation
with c-myc in NDEA induced hepatocarcinogenesis, its pre-
vention by d-limonene.
Mol Biol Rep
30: 41–46.
Penalver P, Huerta B, Borge C, Astorga R, Romero R, Perea A.
2005. Antimicrobial activity of five essential oils against
origin strains of the Enterobacteriaceae family.
APMIS
113:
1–6.
Prashar A, Locke I, Evans C. 2004. Cytotoxicity of lavender oil
and its major components to human skin cells.
Cell Prolif
37: 221–229.
Primo V, Rovera M, Zanon S
et al.
2001. Determination of
the antibacterial and antiviral activity of the essential
oil from
Minthostachys verticillata
(Griseb.) Epling.
Rev.
Argent Microbiol
33: 113–117.
Puatanachokchai R, Kishida H, Denda A
et al.
2002. Inhibitory
effects of lemon grass (
Cymbopogon citratus
, Stapf)
extract on the early phase of hepatocarcinogenesis after
initiation with diethylnitrosamine in male Fischer 344 rats.
Cancer Lett
183: 9–15.
Rajesh D, Howard P. 2003. Perillyl alcohol mediated radio-
sensitization via augmentation of the Fas pathway in pros-
tate cancer cells.
Prostate
57: 14 –23.
Rajesh D, Stenzel R, Howard S. 2003. Perillyl alcohol as a
radio-/chemosensitizer in malignant glioma.
J Biol Chem
278: 35968 –35978.
Reichling J, Fitzi J, Hellmann K, Wegener T, Bucher S, Saller
R. 2004. Topical tea tree oil effective in canine localised
pruritic dermatitis – a multi-centre randomized double-blind
controlled clinical trial in the veterinary practice.
Dtsch
Tierarztl Wochenschr
111: 408–414.
Ren Z, Gould M. 1998. Modulation of small G protein iso-
prenylation by anticancer monoterpenes in
in situ
mam-
mary gland epithelial cells.
Carcinogenesis
19: 827–832.
Rendu F, Daveloose D, Debouzy J
et al.
1989. Ajoene, the
antiplatelet compound derived from garlic, specifically
inhibits platelet release reaction by affecting the plasma
membrane internal microviscosity.
Biochem Pharmacol
38:
1321–1328.
Reybrouck G. 1986. Handwashing and hand disinfection.
J Hosp
Infect
8: 5–23.
Romaguera C, Vilaplana J. 2000. Occupational contact dermati-
tis from ylang-ylang oil.
Contact Derm
43: 251–257.
Samaila D, Toy B, Wang R, Elegbede A. 2004. Monoterpenes
enhanced the sensitivity of head and neck cancer cells to
radiation treatment
in vitro
.
Anticancer Res
24: 3089– 3095.
Santoyo S, Cavero S, Jaime L, Ibanez E, Senorans J, Reglero G.
2006. Supercritical carbon dioxide extraction of compounds
THERAPEUTIC POTENTIAL OF ESSENTIAL OILS 15
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
with antimicrobial activity from
Origanum
vulgare
L.: deter-
mination of optimal extraction parameters.
J Food Prot
69:
369–375.
Scardamaglia L, Nixon R, Fewings J. 2003. Compound tincture
of benzoin: a common contact allergen?
Australas J
Dermatol
44: 180–184.
Schmidt E, Jirovetz L, Buchbauer G
et al.
2005. Antimicrobial
testing and gas chromatographic analysis of aroma chemi-
cals.
J Essential Oil Bearing Plants
8: 99–106.
Schnitzler P, Schon K, Reichling J. 2001. Antiviral activity of
Australian tea tree oil and eucalyptus oil against herpes
simplex virus in cell culture.
Pharmazie
56: 343–347.
Schnuch A, Lessmann H, Geier J, Frosch P, Uter W. 2004.
Contact allergy to fragrances: frequencies of sensitization
from 1996 to 2002. Results of the IVDK.
Contact Derm
50:
65–76.
Schuhmacher A, Reichling J, Schnitzler P. 2003. Virucidal effect
of peppermint oil on the enveloped viruses herpes sim-
plex virus type 1 and type 2
in vitro
.
Phytomedicine
10:
504– 510.
Seymour R. 2003. Additional properties and uses of essential
oils.
J Clin Periodontol
30(S5): 19–21.
Shkurupii V, Kazarinova N, Ogirenko A, Nikonov S, Tkachev A,
Tkachenko K. 2002. Efficiency of the use of peppermint
(
Mentha piperita
L) essential oil inhalations in the com-
bined multi-drug therapy for pulmonary tuberculosis.
Probl
Tuberk
4: 36–39.
Sinico C, De Logub A, Laia F
et al.
2005. Liposomal incorpora-
tion of
Artemisia arborescens
L. essential oil and
in vitro
antiviral activity.
Eur J Pharm Biopharm
59: 161–168.
Sirinivas SR. 1986.
Atlas of Essential Oil
. EA Weiss: Bronx, NY,
USA
Skocibusic M, Bezic N, Dunkic V, Radonic A. 2004. Antibacterial
activity of
Achillea clavennae
essential oil against respira-
tory tract pathogens.
Fitoterapia
75: 733–736.
Snow L, Hovanec L, Brandt J. 2004. A controlled trial of
aromatherapy for agitation in nursing home patients with
dementia.
J Altern Complement Med
10: 431–437.
Sokmen A, Gulluce M, Akpulat A
et al.
2004. The
in vitro
anti-
microbial and antioxidant activities of the essential oils and
methanol extracts of endemic
Thymus
spathulifolius
.
Food
Control
15: 627–634.
Srivastava K. 1986. Onion exerts antiaggregatory effects by
altering arachidonic acid metabolism in platelets.
Prostaglandins Leukot Med
24: 3–50.
Srivastava K, Tyagi O. 1993. Effects of garlic-derived principle
(ajoene) on aggregation and arachidonic acid metabolism
in human blood platelets.
Prostaglandins Leukot Essential
Fatty Acids
49: 587–595.
Steinberg D. 1997. Low density lipoprotein oxidation and its
pathobiological significance.
J Biol Chem
272: 20963– 20966.
Stratton S, Dorr R, Alberts D. 2000. The state-of-the-art in
chemoprevention of skin cancer.
Eur J Cancer
36: 1292–
1297.
Takahashi Y, Inaba N, Kuwahara S, Kuki W. 2003. Antioxidative
effect of Citrus essential oil components on human low-
density lipoprotein
in vitro
.
Biosci Biotechnol Biochem
67:
195–197.
Talpur N, Echard B, Ingram C, Bagchi D, Preuss H. 2005. Effects
of a novel formulation of essential oils on glucose-insulin
metabolism in diabetic and hypertensive rats: a pilot study.
Diabetes Obes Metab
7: 193–199.
Tan P, Zhong W, Cai W. 2000. Clinical study on treatment of
40 cases of malignant brain tumor by elemene emulsion
injection.
Zhongguo Zhong Xi Yi Jie He Za Zhi
(
Chin J Integ
Trad Western Med
) 20: 645 648. Abstract is in English and
available on www.pubmed.org.
Teissedre P, Waterhouse A. 2000. Inhibition of oxidation of
human low-density lipoproteins by phenolic substances in
different essential oils varieties.
J Agric Food Chem
48:
3801–3805.
Tepe B, Donmez E, Unlub M
et al.
2004. Antimicrobial and
antioxidative activities of the essential oils and methanol
extracts of
Salvia cryptantha
(Montbret et Aucher ex Benth.)
and
Salvia multicaulis
(Vahl).
Food Chem
84: 519– 525.
Tepe B, Sokmen M, Akpulat A, Daferera D, Polissiou M, Sokmen
A. 2005. Antioxidative activity of the essential oils of
Thy-
mus sipyleus
subsp.
sipyleus
var.
sipyleus
and
Thymus
sipyleus
subsp.
sipyleus
var.
rosulans
.
J Food Eng
66: 447–
454.
Thomas N, Panchagnula R. 2003. Combination strategies to
enhance transdermal permeation of zidovudine (AZT).
Pharmazie
58: 895–898.
Thomson M, Ali M. 2003. Garlic: A review of its potential
use as an anti-cancer agent.
Curr Cancer Drug Targets
3:
67–81.
Tomaino A, Cimino F, Zimbalatti V
et al.
2005. Influence of
heating on antioxidant activity and the chemical com-
position of some spice essential oils.
Food Chem
89: 549–
554.
Ultee A, Bennik M, Moezelaar R. 2002. The phenolic hydroxyl
group of carvacrol is essential for action against the food-
borne pathogen
Bacillus cereus
.
Appl Environ Microbiol
68:
1561–1568.
Ultee A, Kets W, Smid E. 1999. Mechanisms of action of carvacrol
on the food-borne pathogen
Bacillus cereus
.
Appl Environ
Microbiol
65: 4606– 4610.
Vaddi H, Ho P, Chan Y, Chan S. 2002. Terpenes in ethanol:
haloperidol permeation and partition through human
skin and stratum corneum changes.
J Control Rel
81: 121–
133.
Valenzuela A, Sanhueza J, Alonso P, Corbari A, Nieto S. 2004.
Inhibitory action of conventional food-grade natural anti-
oxidants and of natural antioxidants of new development
on the thermal-induced oxidation of cholesterol.
Int J Food
Sci Nutr
55: 155–162.
Van De Graaff E, Steinhubl S. 2001. Complications of oral
antiplatelet medications.
Curr Cardiol Rep
3: 371–379.
Veien N, Rosner K, Skovgaard G. 2004. Is tea tree oil an impor-
tant contact allergen?
Contact Derm
50: 378– 379.
Vilaplana J, Romaguera C. 2002. Contact dermatitis from the
essential oil of tangerine in fragrance.
Contact Derm
46:
108–113.
Villar R, Maria A, Ramon F. 1997. Inhibition by ajoene of
protein tyrosine phosphatase activity in human platelets.
Biochim Biophys Acta
1337: 233–240.
Vinitketkumnuen U, Lertprasertsuk N. 1997. Inductive and
suppressive effects of crude lemongrass on phase II
xenobiotic-metabolizing enzymes.
Mutat Res/Fund Mol Mech
Mutagen
379(1) (Suppl): S179.
Wagstaff A, Faulds D, Gona K. 1994. Acyclovir: a reappraisal of
its antiviral activity. Pharmocokinetic properties and thera-
peutic efficacy.
Drugs
47: 153–205.
Wannissorn B, Jarikasem S, Siriwangchai T, Thubthimthed S.
2005. Antibacterial properties of essential oils from Thai
medicinal plants.
Fitoterapia
76: 233– 236.
Wattenberg L. 1992. Inhibition of carcinogenesis by minor
dietary constituents.
Cancer Res
52: 2085s– 2091s.
Wendakoon C, Sakaguchi M. 1995. Inhibition of amino acid
decarboxylase activity of
Enterobacter aerogenes
by active
components in spices.
J Food Prot
58: 280–283.
Williams A, Barry B. 1989. Essential oils as novel human skin
penetration enhancers.
Int J Pharm
57: R7–R9.
Williams A, Barry B. 1991. Terpenes and the lipid-protein-
partitioning theory of skin penetration enhancement.
Pharm
Res
8: 17–24.
Williams A, Barry B. 2004. Penetration enhancers.
Adv Drug
Delivery Rev
56: 603–618.
Wu C, Chung J, Tsai S, Yang J, Sheen L. 2004. Differential
effects of allyl sulfides from garlic essential oil on cell cycle
regulation in human liver tumor cells.
Food Chem Toxicol
42: 1937–1947.
Wu C, Sheen L, Chen H, Kuo W, Tsai S, Li C. 2002. Differential
effects of garlic essential oil and its three major organo-
sulfur components on the hepatic detoxification system in
rats.
J Agric Food Chem
50: 379– 383.
Yamada K, Mimaki Y, Sashida Y. 2005. Effects of inhaling the
vapor of
Lavandula burnatii
super-derived essential oil and
linalool on plasma adrenocorticotropic hormone (ACTH),
catecholamine and gonadotropin levels in experimental
menopausal female rats.
Biol Pharm Bull
28: 378 –379.
Yamada K, Miura T, Mimaki Y, Sashida Y. 1996. Effects of
inhalation of chamomile oil vapours on plasma ACTH level
in ovariectomized rat under restriction stress.
Biol Pharm
Bull
19: 1244 –1246.
Yasni S, Imaizumi K, Sin K, Sugano M, Nonaka G. 1994.
Identification of an active principle in essential oils and
hexane-soluble fractions of
Curcuma xanthorrhiza
Roxb.
showing triglyceride-lowering action in rats.
Food Chem
Toxicol
32: 273–278.
Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. (in press)
DOI: 10.1002/ptr
16 A. E. EDRIS
Yazdanparast R Alavi M. 2001. Antihyperlipidaemic and
antihyper-cholesterolaemic effects of
Anethum graveolens
leaves after the removal of furocoumarins.
Cytobios
105:
185–191.
Yengopal V. 2004a. The use of essential oil mouthwashes
as preprocedural rinses for infection control.
SADJ
59: 247–
248, 250.
Yengopal V. 2004b. Essential oils: some lesser known uses and
properties for improved oral health.
SADJ
59: 381–382, 384.
Yengopal V. 2004c. Essential oils and interdental hygiene.
SADJ
59: 155, 157, 170.
Yengopal V. 2004d. Preventative dentistry: essential oils and
oral malodour.
SADJ
59: 204, 206.
Yuri T, Danbara N, Tsujita-Kyutoku M
et al.
2004. Perillyl alcohol
inhibits human breast cancer cell growth
in vitro
and
in
vivo
.
Breast Cancer Res Treat
84: 251–260.
Zarkovic N. 2003. 4-Hydroxynonenal as a bioactive marker of
pathophysiological processes.
Mol Aspects Med
24: 281–
291.
Zheng G, Kenny P, Lam L. 1992. Inhibition of benzo[a]-pyrene-
induced tumorigenesis by myristicin, a volatile aroma
constituent of parsley leaf oil.
Carcinogenesis
13: 1921–1923.
Project
To advance the clinical development of thymoquinone (from Monarda) alone or in combination with chemotherapy agents for cancer therapy.
Article
Full-text available
January 2011
    Essential oils have been important substances since early times. The review of its extraction methods and applications were treated in this study. These include hydrodistillation, hydrodiffusion, effleurage, steam distillation, cold pressing, solvent extraction, microwave assisted process and carbondioxide extraction. Its applications both the medicinal and therapeutics, such as aromatherapy,... [Show full abstract]
    Article
      Tea tree oil (TTO) comes from the leaves of Melaleuca alternifornia that belongs to the myrtle family (Myrtaceae). It is one of the most powerful immune system stimulants and sorts out most viral, bacterial and fungal infections in a snap, while it is great to heal wounds and acnes. In Vietnam, Melaleuca trees can grow on acid land that stretches in a large portion of lands in the Mekong Delta... [Show full abstract]
      Article
        Tea tree oil is an essential oil obtained by steam distillation of the leaves and terminal branches of Melaleuca alternifolia. In recent years, it has become popular as an antimicrobial agent against a large number of diseases. It is a natural substance that has a potential toxic effect especially if ingested. We report two cases of infants who came to our Emergency Department because they... [Show full abstract]
        Discover more