Biological effects of essential oils – A review
F. Bakkalia,b, S. Averbecka, D. Averbecka,*, M. Idaomarb
aInstitut Curie-Section de Recherche, UMR2027 CNRS/IC, LCR V28 CEA, Ba ˆt. 110, Centre Universitaire, 91405 Orsay cedex, France
bUniversite ´ Abdelmalek Essa ˆadi, Faculte ´ des Sciences, Laboratoire de Biologie et Sante ´, BP 2121, Te ´touan, Morocco
Since the middle ages, essential oils have been widely used for bactericidal, virucidal, fungicidal, antiparasitical, insecticidal, medicinal
and cosmetic applications, especially nowadays in pharmaceutical, sanitary, cosmetic, agricultural and food industries. Because of the
mode of extraction, mostly by distillation from aromatic plants, they contain a variety of volatile molecules such as terpenes and terpe-
noids, phenol-derived aromatic components and aliphatic components. In vitro physicochemical assays characterise most of them as anti-
oxidants. However, recent work shows that in eukaryotic cells, essential oils can act as prooxidants affecting inner cell membranes and
organelles such as mitochondria. Depending on type and concentration, they exhibit cytotoxic effects on living cells but are usually non-
genotoxic. In some cases, changes in intracellular redox potential and mitochondrial dysfunction induced by essential oils can be asso-
ciated with their capacity to exert antigenotoxic effects. These findings suggest that, at least in part, the encountered beneficial effects of
essential oils are due to prooxidant effects on the cellular level.
Keywords: Essential oil; Cytotoxicity; Genotoxicity; Antigenotoxicity; Prooxidant activity
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447
Chemical composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447
2.1.Terpenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.Aromatic compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
3.1.Cytotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2. Phototoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3. Nuclear mutagenicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4.Cytoplasmic mutagenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5.Carcinogenicity of the essential oils. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.6.Antimutagenic properties of essential oils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Underlying mechanisms: mitochondrial damage and prooxidant cytotoxic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
Specificity of essential oils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
Synergism between the components of essential oils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
Medicinal and future medical applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467
*Corresponding author. Tel.: +33 169867188; fax: +33 169869429.
E-mail address: email@example.com (D. Averbeck).
Essential oils are volatile, natural, complex compounds
characterized by a strong odour and are formed by aro-
matic plants as secondary metabolites. They are usually
obtained by steam or hydro-distillation first developed in
the Middle Ages by Arabs. Known for their antiseptic,
i.e. bactericidal, virucidal and fungicidal, and medicinal
properties and their fragrance, they are used in embalment,
preservation of foods and as antimicrobial, analgesic, sed-
ative, anti-inflammatory, spasmolytic and locally anesthe-
sic remedies. Up to the present day, these characteristics
have not changed much except that more is now known
about some of their mechanisms of action, particularly at
the antimicrobial level.
In nature, essential oils play an important role in the
protection of the plants as antibacterials, antivirals, anti-
fungals, insecticides and also against herbivores by reduc-
ing their appetite for such plants. They also may attract
some insects to favour the dispersion of pollens and seeds,
or repel undesirable others.
Essential oils are extracted from various aromatic plants
generally localized in temperate to warm countries like
Mediterranean and tropical countries where they represent
an important part of the traditional pharmacopoeia. They
are liquid, volatile, limpid and rarely coloured, lipid soluble
and soluble in organic solvents with a generally lower den-
sity than that of water. They can be synthesized by all plant
organs, i.e. buds, flowers, leaves, stems, twigs, seeds, fruits,
roots, wood or bark, and are stored in secretory cells, cav-
ities, canals, epidermic cells or glandular trichomes.
There are several methods for extracting essential oils.
These may include use of liquid carbon dioxide or micro-
waves, and mainly low or high pressure distillation employ-
ing boiling water or hot steam. Due to their bactericidal
and fungicidal properties, pharmaceutical and food uses
are more and more widespread as alternatives to synthetic
chemical products to protect the ecological equilibrium. In
those cases, extraction by steam distillation or by expres-
sion, for example for Citrus, is preferred. For perfume uses,
extraction with lipophilic solvents and sometimes with
supercritical carbon dioxide is favoured. Thus, the chemi-
cal profile of the essential oil products differs not only in
the number of molecules but also in the stereochemical
types of molecules extracted, according to the type of
extraction, and the type of extraction is chosen according
to the purpose of the use. The extraction product can vary
in quality, quantity and in composition according to cli-
mate, soil composition, plant organ, age and vegetative
cycle stage (Masotti et al., 2003; Angioni et al., 2006). So,
in order to obtain essential oils of constant composition,
they have to be extracted under the same conditions from
the same organ of the plant which has been growing on
the same soil, under the same climate and has been picked
in the same season. Most of the commercialized essential
oils are chemotyped by gas chromatography and mass
spectrometry analysis. Analytical monographs have been
published (European pharmacopoeia, ISO, WHO, Council
of Europe; Smith et al., 2005) to ensure good quality of
Essential oils have been largely employed for their prop-
erties already observed in nature, i.e. for their antibacterial,
antifungal and insecticidal activities. At present, approxi-
mately 3000 essential oils are known, 300 of which are
commercially important especially for the pharmaceutical,
agronomic, food, sanitary, cosmetic and perfume indus-
tries. Essential oils or some of their components are used
in perfumes and make-up products, in sanitary products,
in dentistry, in agriculture, as food preservers and addi-
tives, and as natural remedies. For example, d-limonene,
geranyl acetate or d-carvone are employed in perfumes,
creams, soaps, as flavour additives for food, as fragrances
for household cleaning products and as industrial solvents.
Moreover, essential oils are used in massages as mixtures
with vegetal oil or in baths but most frequently in
aromatherapy. Some essential oils appear to exhibit partic-
ular medicinal properties that have been claimed to cure
one or another organ dysfunction or systemic disorder
(Silva et al., 2003; Hajhashemi et al., 2003; Perry et al.,
Owing to the new attraction for natural products like
essential oils, despite their wide use and being familiar to
us as fragrances, it is important to develop a better under-
standing of their mode of biological action for new applica-
tions in human health, agriculture and the environment.
Some of them constitute effective alternatives or comple-
ments to synthetic compounds of the chemical industry,
without showing the same secondary effects (Carson and
2. Chemical composition
Essential oils are very complex natural mixtures which
can contain about 20–60 components at quite different con-
centrations. They are characterized by two or three major
components at fairly high concentrations (20–70%) com-
pared to others components present in trace amounts.
For example, carvacrol (30%) and thymol (27%) are the
major components of the Origanum compactum essential
oil, linalol (68%) of the Coriandrum sativum essential oil,
a- and b-thuyone (57%) and camphor (24%) of the Artemi-
sia herba-alba essential oil, 1,8-cineole (50%) of the Cinna-
momum camphora essential oil, a-phellandrene (36%) and
limonene (31%) of leaf and carvone (58%) and limonene
(37%) of seed Anethum graveolens essential oil, menthol
(59%) and menthone (19%) of Mentha piperita(=Men-
tha · piperita) essential oil. Generally, these major compo-
nents determine the biological properties of the essential
oils. The components include two groups of distinct bio-
synthetical origin (Croteau et al., 2000; Betts, 2001; Bowles,
2003; Pichersky et al., 2006). The main group is composed
of terpenes and terpenoids and the other of aromatic and
aliphatic constituents, all characterized by low molecular
weight (see Fig. 1).
Cymene (“y”) or p.cymene Sabinene
2. Aromatic compounds
Methylene dioxy compound
3. Terpenoides (Isoprenoides)
Fig. 1. Chemical structures of selected components of essential oils.
Terpenes form structurally and functionally different
classes. They are made from combinations of several 5-car-
bon-base (C5) units called isoprene. The biosynthesis of the
terpenes consists of synthesis of the isopentenyl diphos-
phate (IPP) precursor, repetitive addition of IPPs to form
the prenyldiphosphate precursor of the various classes of
terpenes, modification of the allylic prenyldiphosphate by
terpene specific synthetases to form the terpene skeleton
and finally, secondary enzymatic modification (redox reac-
tion) of the skeleton to attribute functional properties to
the different terpenes. The main terpenes are the monoter-
penes (C10) and sesquiterpenes (C15), but hemiterpenes
(C5), diterpenes (C20), triterpenes (C30) and tetraterpenes
(C40) also exist. A terpene containing oxygen is called a
The monoterpenes are formed from the coupling of two
isoprene units (C10). They are the most representative mol-
ecules constituting 90% of the essential oils and allow a
great variety of structures. They consist of several
acyclic: myrcene, ocimene, etc.
monocyclic: terpinenes, p-cimene, phellandrenes, etc.
bicyclic: pinenes, -3-carene, camphene, sabinene, etc.
acyclic: geraniol, linalol, citronellol, lavandulol,
monocyclic: menthol, a-terpineol, carveol
bicyclic: borneol, fenchol, chrysanthenol, thuyan-3-
acyclic: geranial, neral, citronellal, etc.
acyclic: tegetone, etc.
monocyclic: menthones, carvone, pulegone, piperito-
bicyclic: camphor, fenchone, thuyone, ombellulone,
pinocamphone, pinocarvone, etc.
acyclic: linalyl acetate or propionate, citronellyl ace-
monocyclic: menthyl or a-terpinyl acetate, etc.
bicyclic: isobornyl acetate, etc.
1,8-cineole, menthofurane, etc.
Peroxydes: ascaridole, etc.
Phenols: thymol, carvacrol, etc.
When the molecule is optically active, the two enantio-
mers are very often present in different plants: (+)-a-pinene
from Pinus palustris, (?)-b-pinene from Pinus caribaea
and from Pinus pinaster, (?)linalol from coriander,
(+)-linalol from some camphor trees, etc. In some cases,
it is the racemic form which is the most frequently encoun-
tered: (±)-citronellol is widespread, the form (+) is charac-
teristic of Eucalyptus citriodora, the form (?) is common to
the rose and geranium essential oils.
The sesquiterpenes are formed from the assembly of
three isoprene units (C15). The extension of the chain
increases the number of cyclisations which allows a great
variety of structures. The structure and function of the ses-
quiterpenes are similar to those of the monoterpenes:
Carbures: azulene, b-bisabolene, cadinenes, b-caryo-
phyllene, logifolene, curcumenes, elemenes, farnesenes,
Alcohols: bisabol, cedrol, b-nerolidol, farnesol, carotol,
b-santalol, patchoulol, viridiflorol, etc.
Ketones: germacrone, nootkatone, cis-longipinan-2,7-
dione, b-vetinone, turmerones, etc.
Epoxide: caryophyllene oxide, humulene epoxides, etc.
Examples of plants containing these compounds are
angelica, bergamot, caraway, celery, citronella, coriander,
eucalyptus, geranium, juniper, lavandin, lavander, lemon,
lemongrass, mandarin, mint, orange, peppermint, petit-
grain, pine, rosemary, sage, thyme.
2.2. Aromatic compounds
Derived from phenylpropane, the aromatic compounds
occur less frequently than the terpenes. The biosynthetic
pathways concerning terpenes and phenylpropanic deriva-
tives generally are separated in plants but may coexist in
some, with one major pathway taking over (see, cinnamom
oil with cinnamaldehyde as major and eugenol as minor
constituents, also clove oil, fennel, etc.).
Aromatic compounds comprise:
Alcohol: cinnamic alcohol
Phenols: chavicol, eugenol
Methoxy derivatives: anethole, elemicine, estragole,
Methylene dioxy compounds: apiole, myristicine, safrole
The principal plant sources for these compounds are
anise, cinnamon, clove, fennel, nutmeg, parsley, sassafras,
star anise, tarragon, and some botanical families (Apia-
ceae, Lamiaceae, Myrtaceae, Rutaceae).
Nitrogenous or sulphured components such as glucosin-
olates or isothiocyanate derivatives (garlic and mustard
oils) are also characteristic as secondary metabolites of
diverse plants or of torrefied, grilled or roasted products.
3. Biological effects
Because of the great number of constituents, essential
oils seem to have no specific cellular targets (Carson
et al., 2002). As typical lipophiles, they pass through the
cell wall and cytoplasmic membrane, disrupt the structure
of their different layers of polysaccharides, fatty acids and
appears to include such membrane damage. In bacteria,
the permeabilization of the membranes is associated with
loss of ions and reduction of membrane potential, collapse
of the proton pump and depletion of the ATP pool (Knob-
loch et al., 1989; Sikkema et al., 1994; Helander et al., 1998;
Ultee et al., 2000, 2002; Di Pasqua et al., 2006; Turina
et al., 2006). Essential oils can coagulate the cytoplasm
(Gustafson et al., 1998) and damage lipids and proteins
(Ultee et al., 2002; Burt, 2004). Damage to the cell wall
and membrane can lead to the leakage of macromolecules
and to lysis (Juven et al., 1994; Gustafson et al., 1998; Cox
et al., 2000; Lambert et al., 2001; Oussalah et al., 2006).
In eukaryotic cells, essential oils can provoke depolar-
isation of the mitochondrial membranes by decreasing
the membrane potential, affect ionic Ca++cycling (Richter
and Schlegel, 1993 ; Novgorodov and Gudz, 1996 ; Vercesi
et al., 1997) and other ionic channels and reduce the pH
gradient, affecting (as in bacteria) the proton pump and
the ATP pool. They change the fluidity of membranes,
which become abnormally permeable resulting in leakage
of radicals, cytochrome C, calcium ions and proteins, as
in the case of oxidative stress and bioenergetic failure. Per-
meabilization of outer and inner mitochondrial membranes
leads to cell death by apoptosis and necrosis (Yoon et al.,
2000; Armstrong, 2006). It seems that chain reactions from
the cell wall or the outer cell membrane invade the whole
cell, through the membranes of different organelles like
mitochondria and peroxisomes. These effects suggest a phe-
nolic-like prooxidant activity (Sakagami and Satoh, 1997;
Cowan, 1999; Sakagami et al., 1999; Fukumoto and Maz-
za, 2000; Sakihama et al., 2002; Burt, 2004; Barbehenn
et al., 2005). Scanning and transmission electron micros-
copy observations reveal cell ultrastructural alterations in
several compartments such as plasma membrane, cyto-
plasm (swelling, shrivelling, vacuolations, leakage) and
nucleus (Soylu et al., 2006; Santoro et al., 2007a,b). Anal-
yses of the lipid profiles by gas chromatography and of the
cell envelope structure by scanning electron microscopy of
several bacteria treated by some essential oil constituents
showed a strong decrease in unsaturated and an increase
in saturated fatty acids, as well as alterations of the cell
envelopes (Di Pasqua et al., 2007). Disruption of the
HSV viral envelope by essential oils could also be observed
by electron microscopy preventing the host cells from infec-
tion (Schnitzler et al., 2007). The induction of membrane
damages has been also confirmed by a microarray analysis
showing that Saccharomyces cerevisiae genes involved in
ergosterol biosynthesis and sterol uptake, lipid metabolism,
cell wall structure and function, detoxification and cellular
transport are affected by a treatment with a-terpinene, a
monocyclic monoterpene (Parveen et al., 2004).
Cytotoxic effects were observed in vitro in most of path-
ogenic gram positive and gram negative bacteria by agar
diffusion method using a filter paper disc or by the dilution
method using agar or liquid broth cultures (Williams et al.,
1998; Kalemba and Kunicka, 2003; Arnal-Schnebelen
et al., 2004; Burt, 2004; Hong et al., 2004; Rota et al.,
2004; Si et al., 2006; Sonboli et al., 2005, 2006a,b), in
ADN or ARN virus (Hayashi et al., 1995; De Logu
et al., 2000; Jassim and Naji, 2003; Reichling et al., 2005)
and in fungi (Manohar et al., 2001; Pitarokili et al., 2002;
Hammer et al., 2002; Kosalec et al., 2005) including yeasts
(Harris, 2002; Hammer et al., 2004; Wang et al., 2005;
Duarte et al., 2005; Pauli, 2006; Carson et al., 2006) (see
Table 1). In particular, recent work in the yeast Saccharo-
myces cerevisiae, has shown that the cytotoxicity of some
essential oils, based on colony forming ability, differed con-
siderably depending on their chemical composition; essen-
tial oil treated cells in stationary phase of growth showed
50% lethality at 0.45 lL/mL of Origanum compactum
essential oil, 1.6 lL/mL of Coriandrum sativum essential
oil, >8 lL/mL of Cinnamomum camphora, Artemisia
herba-alba and Helichrysum italicum essential oils (Bakkali
et al., 2005). Moreover, it depended also on the state of cell
growth, dividing cells being much more sensitive probably
because essential oils penetrated more efficiently at the bud-
ding sites. In general, the cytotoxic activity of essential oils
is mostly due to the presence of phenols, aldehydes and
alcohols (Bruni et al., 2003; Sacchetti et al., 2005).
This cytotoxic property is of great importance in the
applications of essential oils not only against certain
human or animal pathogens or parasites but also for the
preservation of agricultural or marine products. Essential
oils or some of their constituents are indeed effective
against a large variety of organisms including bacteria
(Holley and Dhaval, 2005; Basile et al., 2006; Schelz
et al., 2006; Hu ¨snu ¨ Can Baser et al., 2006), virus (Dus-
chatzky et al., 2005), fungi (Hammer et al., 2002; Velluti
et al., 2003, 2004; Serrano et al., 2005; Cavaleiro et al.,
2006; Pawar and Thaker, 2006; Soylu et al., 2006), proto-
zoa (Monzote et al., 2006), parasites (Moon et al., 2006;
Priestley et al., 2006), acarids (Rim and Jee, 2006), larvae
(Hierro et al., 2004; Pavela, 2005; Morais et al., 2006; Amer
and Mehlhorn, 2006a,b; Ravi Kiran et al., 2006), worms,
insects (Bhatnagar et al., 1993; Lamiri et al., 2001; Liu
et al., 2006; Burfield and Reekie, 2005; Yang and Ma,
2005; Sim et al., 2006; Kouninki et al., 2005; Park et al.,
2006a,b; Chaiyasit et al., 2006; Cheng et al., 2007) and mol-
luscs (Lahlou and Berrada, 2001) (see Table 2).
Cytotoxic activities of essential oils or their major com-
ponents, sometimes activated by light, were also demon-
strated in mammalian cells in vitro by short-term viability
assays using specific cell staining or fluorescent dyes includ-
ing NRU (Neutral Red Uptake) test (So ¨derberg et al.,
1996; Stammati et al., 1999; Dijoux et al., 2006), MTT
mide) test (Fujisawa et al., 2002; Carvalho de Sousa
et al., 2004; Sun et al., 2005b; Yoo et al., 2005; Manosroi
et al., 2006; Jafarian et al., 2006; Chung et al., 2007), Ala-
mar Blue (resazurin) test (O’Brien et al., 2000), Trypan
Blue exclusion test (Budhiraja et al., 1999; Horvathova
et al., 2006; Slamenova et al., 2007) or Hoechst 33342
Examples of essential oils tested for their cytotoxic capacities on standard organisms
EOs or componentsOrganisms ConcentrationsReferences
Penicillium sp., Alternaria sp.
50 lL of dilutions 1/2, 1/4, 1/8, 1/16
on filter paper discs
Hong et al. (2004)
1, 0.8, 0.5, 0.3 mg/mL
0.5, 2, 4 mg/filter paper disc
MICs 0.3, 0.5, 0.8 mg/mL
80, 200, 500 lg/disc
(no antifungal activity)
Saı¨dana et al. (2007)
Sartorelli et al. (2007)
0.25–1% (v/v) Hammer et al. (2004)
ED50 0.00038–0.0091% w/v
ED50 0.0015–0.0062% w/v
2-fold dilution for EO
0.0083% for components
Hammer et al. (2002)
Hayashi et al. (1995)
Mimica-Dukic et al. (2004)
MIC 15–30 lL/mL
MIC 8–15–30 lL/mL
MIC 1–2 lL/mL
MIC 2–4 lL/mL
IC50 0.58, 0.96 lg/mL
Bozin et al. (2006)
Lavandula latifolia (a),
Lavandula angustifolia (b),
Three hybrids a · b
HSV-1, HSV-2 Reichling et al. (2005)
MIC < 0.1–5.0 lL/mLRota et al. (2004)
EC50 492.55 lL/L
EC50 544.17 lL/L
EC50 584.36 lL/L
EC50 549.62 lL/L
EC50 > 1500 lL/L
EC50 > 1500 lL/L
EC50 146.15 lL/L
EC50 563.94 lL/L
EC50 661.76 lL/L
Pitarokili et al. (2002)
(continued on next page)
Table 1 (continued)
EOs or componentsOrganisms Concentrations References
MIC > ou = 2000 lL/L
MIC > 500 lL/L
Pitarokili et al. (2003)
MIC 2 or >2 mg/mL
MIC 1.5–2 mg/mL
MIC 0.250–1 or >2 mg/mL
MIC 1–2 or >2 mg/mL
Peana et al. (1999)
MIC 0.5–1.9 mg/mL
MIC 7.5–15 mg/mL
MIC 0.2–2.5 mg/mL
MIC 0.6–5 mg/mL
Sonboli et al. (2005)
10 lL/filter paper disc
MIC 3.75 to >15 mg/mL
MIC 1.8–7.2 mg/mL
MIC 0.9–7.2 mg/mL
Sonboli et al. (2006b)
MIC 0.1–1.56% v/v Kosalec et al. (2005)
a-Pinene, Borneol, Thymol,
Carvacrol, Cineole, p-Cimene
Linalool, Menthone, R-(+)-Pulegone
Manohar et al. (2001)
Bouchra et al. (2003)
Bagamboula et al. (2004)
4.50,0.09, 0.04, 0.02 lg per
filter paper disc agar
IZ: inactive to 36 mm
Kubo et al. (2004)
Singh et al. (2002)
Table 1 (continued)
EOs or componentsOrganisms Concentrations References
Carum nigrum essential oil,
oleoresin and components
Group A Streptococcus
2000, 3000 ppmSingh et al. (2006)
Coriandrum sativum (seeds)
Coriandrum sativum (leaves)
Eucalyptus dives and fractions
MIC 0.02–0.10–0.47% v/v
MIC 0.02–0.10–0.47% v/v
MIC 0.01–0.10–0.47% v/v
MIC 0.04–0.13–0.43% v/v
Delaquis et al. (2002)
500, 750, 1000 ppmBasilico and Basilico (1999)
18 ATCC and clinical bacteria
MIC 5–25 lg/mL
MIC 3.9, 7.8 lg/mL
MIC 15.6, 7.8 lg/mL
MIC 15.6 lg/mL
MIC 7.8 lg/mL
5 lL/filter paper disc
IC50 5, 2 lg/mL
IC50 7, 1.5 lg/mL
Basile et al. (2006)
75 essential oils
Pawar and Thaker (2006)
Saleh et al. (2006)
MIC 0.06–1.0 mg/mL Hu ¨snu ¨ Can Baser et al. (2006)
Pulegone, Menthone, Carvone
Gopanraj et al. (2005)
Franzios et al. (1997)0.2–2.1 lL on paper disc
MIC 26–2592 lg/mL Lee et al. (2007a)
21 essential oils of
Eucalyptus, Lime, etc.
MIC 0.625–10 mg/mL Botelho et al. (2007)
1/1, 1/5, 1/10, 1/20
MIC 0.2–25.6 mg/mL
Prabuseenivasan et al. (2006)
(continued on next page)
Table 1 (continued)
EOs or componentsOrganisms ConcentrationsReferences
16 plant bacteria
15 food bacteria
33 clinic bacteria
14 gram-positive and
20 lL/20 mL agar
600, 900, 1200 lg/disc
Kordali et al. (2005)
4.5 mg/agar petridish
MIC 0.25–1 mg/mL
5, 10 lg/filter paper disc
Hernandez et al. (2005)
Hanbali et al. (2005)
MICs 0.06, 0.14, 0.28,
4.50, 18.00 mg/mL
MIC 8–70% v/v
MIC < 10% v/v
MIC 0.39–2% v/v
MIQ 480–7680 lg
Tepe et al. (2004a,b)
Seven fungi, three yeasts
27 phytopathogenic bacteria
Two mycopathogenic species
Four bacteria, two fungi, two yeasts
Pepeljnjak et al. (2005)
Lo Cantore et al. (2004)
Dob et al. (2006)
Kumar et al. (2007)
29 essential oils
MIC 1.4–11.20 mg/Ml
MIC 0.35–0.70 mg/mL
MIC 0.36–5.60 mg/mL
MIC 1.40–11.20 mg/mL
MIC 1.40–11.20 mg/mL
MIC 0.28–1.40 mg/mL
MIC 0.35–1.40 mg/mL
MIC 2.80–5.60 mg/mL
MIC 0.08–1.40 mg/mL
MIC 0.7–1.40 mg/mL
MIC 0.35–2.80 mg/mL
MIC 22.40 mg/mL
MIC 100–500 lg/mL
Rosato et al. (2007)
13 Escherichia coli serotypesDuarte et al. (2007)
Eight bacteria, nine fungi, one yeast
MBC 0.62–2.5 vol%
MFC 0.31–1.25 vol%
Pithayanukul et al. (2007)
Song et al. (2007)
IC50 147, 189 lg/mL
MIC 0.78–25.50 lL/mL
Lu et al. (2007)
MIC 0.78–1.56 lg/mL
MIC 62.50–125 lL/mL
MIC 1.0–3.0 lL/mL
MIC 1.0–2.8 lL/mL
MIC 0.8–3.2 lL/mL
Foeniculum vulgare (FE)
(FE1, FE2, FE3)
Ozer et al. (2007)
Mimica-Dukic et al. (2003)
and propidium iodide test (Fabian et al., 2006). Essential
oil cytotoxicity in mammalian cells is caused by induction
of apoptosis and necrosis.
Unscheduled DNA synthesis (UDS) tests were also per-
formed in mammalian cells to detect the presence and
removal of adducts in DNA and repair DNA synthesis.
For instance, eugenol, isoeugenol, methyleugenol and saf-
role induce cytotoxicity and genotoxicity in rat and mouse
hepatocytes, measured respectively by lactate dehydroge-
nase release and UDS (Burkey et al., 2000); UDS was also
induced by Ocimum basilicum essential oil and its main
component, estragole, in hamster fibroblastic V79 cells
(Muller et al., 1994).
Until now, because of their mode of action affecting sev-
eral targets at the same time, generally, no particular resis-
tance or adaptation to essential oils has been described.
However, a resistance to carvacrol of Bacillus cereus has
been observed after growth in the presence of a sublethal
carvacrol concentration. Pre-treatment with carvacrol
diminished the fluidity of the membrane by changing its
fatty acid ratio and composition (Ultee et al., 2000; Di
Pasqua et al., 2006). Increased tolerance of Pseudomonas
aeruginosa to Melaleuca alternifolia essential oil was also
reported involving changes in the barrier and energy func-
tions of the outer membrane (Longbottom et al., 2004).
The same effect was produced by hydrogen peroxide
(Branco et al., 2004). Even with flavonoids, non-toxic con-
centrations protected against quercetin cytotoxicity (Oli-
veira et al., 1997; Dickancaite et al., 1998). Adaptation to
sub-lethal concentrations of Tea Tree oil (Melaleuca
alternifolia) reduced susceptibility to human pathogen anti-
biotics, probably also due to membrane changes inhibiting
antibiotic penetration (McMahon et al., 2007). However,
Rafii and Shahverdi (2007) have found a potentiation of
the antibiotic nitrofurantoin at a sub-inhibitory concentra-
tion by essential oils against enterobacteria. Probably,
given the effect of essential oils on cell membranes, the
bacterial susceptibility or resistance depend on the mode
of application and may suggest that the antibiotic has to
be first in contact with the cells (Rafii and Shahverdi,
Some essential oils contain photoactive molecules like
furocoumarins. For instance, Citrus bergamia (= Citrus
aurantium ssp. bergamia) essential oil contains psoralens
which bind to DNA under ultraviolet A light exposure pro-
ducing mono- and biadducts that are cytotoxic and highly
have shown that Fusanus spicatus wood essential oil was not
phototoxic but was very cytotoxic. In other words, cytotox-
icity seems rather antagonistic to phototoxicity. In the case
of cytotoxicity, essential oils damage the cellular and orga-
nelle membranes and can act as prooxidants on proteins
and DNA with production of reactive oxygen species
(ROS), and light exposures do not add much to the overall
the cell without damaging the membranes or proteins and
DNA. Radical reactions by excitation of certain molecules
and energy transfer with production of oxygen singlet occur
when cells are exposed to activating light. This may cause
damage to cellular macromolecules and in some cases the
formation of covalent adducts to DNA, proteins and mem-
brane lipids. Obviously, cytotoxicity or phototoxicity
depends on the type of molecules present in the essential oils
and their compartmentation in the cell, producing different
types of radicals with or without light exposure. However,
such an antagonism is not quite a strict rule. Dijoux et al.
(2006) have shown that Citrus aurantium dulcis (= Citrus
gracilis subf. dulcis) and Cymbopogon citratus essential oils
were phototoxic and cytotoxic. Thus, when studying an
its cytotoxic as well as its possible phototoxic capacity.
3.3. Nuclear mutagenicity
Several studies with various essential oils or their main
components have demonstrated that, generally, most of
them did not induce nuclear mutations, whatever the
organism, i.e. bacteria, yeast or insect, with or without
metabolic activation and whatever form of essential oils,
Table 1 (continued)
EOs or componentsOrganisms ConcentrationsReferences
MIC 7.0–15.0 lL/mL
MIC 1.3–2.2 lL/mL
MIC 3.7–5.8 lL/mL
MIC 2.8–6.0 lL/mL
MIC: minimum inhibitory concentration, MBC: minimum bactericidal concentration, ED: effective dose, EC: effective concentration, IC: inhibitory
concentration, IZ: inhibition zone, MFC: minimum fungicidal concentration, MIQ: minimal inhibitory quantity.
Examples of environmental, agricultural, food and medical applications of essential oils
EOs or componentsOrganisms ConcentrationsReferences
Lavandula angustifolia, etc.
Hierro et al. (2004)
2, 4, 6, 10, 20 lL/L air Lamiri et al. (2001)
HSV-1, DENV-2, JUNV
500, 1000 lg/g maizeVelluti et al. (2003)
VC50 44.2, 39.0 ppmDuschatzky
et al. (2005)
LC50 10, 20 mL/m3
LD 0.05 lL/larvae
(tomato late blight disease)
0.4–2.0 lg/mL air
6.4, 12.8, 25.6,
Soylu et al. (2006)
Sitophillus oryzae L.,
Bruchus rugimanus Bohem
(storage pests, germination)
production (maize grain)
3.9–250 lg/mL Basile et al. (2006)
Liu et al. (2006)
Oregano and cranberry
500, 1000 mg/kg Velluti et al. (2004)
0.1 mg/filter paper discLin et al. (2005)
Absidia, Mucor, Cladosporium,
Chaetomium, Stachybotrys chartarum
(moulds from damp dwellings)
MIC 20, 50.20 lg/mL
82 lg/L (vapor)
Segvic-Klaric et al. (2007)
Table 2 (continued)
EOs or componentsOrganisms ConcentrationsReferences
Parsley, Thyme, Anis,
(guinea pig infection)
MIC 0.01–0.03 %
MIC 0.5–2 %
LC50 99.5 lg/mL
LC50 57.5 lg/mL
Lee et al. (2007b)
Santoro et al. (2007a)
IC50 175, 115 lg/mL
IC50 77, 38 lg/mL
IC50 62, 53 lg/mL
LC50 15–156 ppm
Santoro et al. (2007b)
Knio et al. (2007)
HSV-1 (acyclovir-sensitive, resistant)
Filter paper discs 1, 5, 10 lL
MIC (flowers) 0.3 lL/mL
MIC (leaves) 0.6 lL/mL
Ioannou et al. (2007)
CC50 0.004% EC50 0.0002%
CC50 0.007% EC50 0.001%
CC50 0.0075% EC50 0.0001%
CC50 0.0015% EC50 0.0002%
LC50 24.61–54.62 ppm
Schnitzler et al. (2007)
Aedes aegypti (larvae)
Pitasawat et al. (2007)
VERO cell line
10 lL/filter paper disc
MIC 0.00125–0.050 lL/mL
Fabio et al. (2007)
250 lL/well of dilutions
MNTC 0.00005–0.0005 lL/mL
IC50 0.8 lg/mL
IC50 14 lg/mL
IC50 1.2 lg/mL
IC50 0.5 lg/mL
8.50 mm lL(?1)
5.63 mm lL(?1)
MCF-7 cell line
Hela cell line
Jafarian et al. (2006)
54 essential oils
Cade, Cardamone ceylon,
Clove, Myrtle, Rosewood,
Dutta et al. (2007)
Pediculus humanus capitis
LT50 (min) at 0.0625,
0.125, 0.25 mg/cm2
LT50 (min) at 0.25 mg/cm2
Yang et al. (2004a)
Yang et al. (2004b)
Pediculus humanus (human louse and eggs)
2 lg/mLHatimi et al. (2001)
Essential oil constituents 600 lL dilutions 10%, 5%,
2%, 1% (w/v, v/v)
Priestley et al. (2006)
Pediculus humanus capitus
Abou El Ela et al. (2004)
(continued on next page)
Table 2 (continued)
EOs or components OrganismsConcentrations References
Cadra cautella (Lepidoptera
Aedes aegypti (larvae)
MIC (leaf) 0.08–10 lL/mL
MIC (berry) 0.32–20 lL/mL
MLC (leaf) 0.08–20 lL/mL
MLC (berry) 0.32–20 lL/mL
Cavaleiro et al. (2006)
44 essential oils2.4, 4.7 mg/cm264.7 mg/L airSim et al. (2006)
41 essential oils from
Dill, Myrtle, Juniper,
Black pepper, Verbena,
Helichrysum, Sandalwood, etc.
11 essential oils from
Nepeta cataria, etc.
Seven essential oils
Annona senegalensis, etc.
Citronella, Mentha · piperita
LC50 84 ppm
LC50 102 ppm
LC50 104 ppm
LC50 28 ppm
LC50 1–101.3 ppm
LC50 9.7–101.4 ppm
LC50 1–50.2 ppm
Morais et al. (2006)
Amer and Mehlhorn
Mixtures of five oils (1% each)
in solvent 100 lL/30 cm2
human arm (repellency)
Amer and Mehlhorn
Sitophilus zeamais (coleoptera)
30 mg/kg mice
1% (contact) 300 lL/800 mL air
Monzote et al. (2006)
Kouninki et al. (2005)
Aedes aegypti (larvae, adult)
Aedes albopictus (mosquito)
LC50 36.30 ppm LC50 2.86 lg/mg
7%, 15% (repellency)
Choochote et al. (2005)
Yang and Ma (2005)
Anopheles stephensi (larvae)
LC50 16.5, 14.9 lg/mL
LC50 28.3, 25.8 lg/mL
LC50 43.4, 41.2 lg/mL
LC50 63.6, 59.5 lg/mL
0.1, 0.05, 0.025, 0.0125,
Ravi Kiran et al. (2006)
Pennyroyal, Ylang Ylang,
Citronella, Lemongrass, Tea tree,
40 essential oils
Rim and Jee (2006)
Lycoriella ingenua (diptera)10, 5 lL/L air
1.25, 0.625 lL/L air
Park et al. (2006a)
LC50 0.15, 0.20,
0.87, 1.47 lL/L air
Table 2 (continued)
EOs or componentsOrganisms ConcentrationsReferences
21 essential oils
Pulegone, Menthone, Limonene
Lycoriella ingenua (larvae)25, 12.5, 3.125 lg/mL air Park et al. (2006b)
LC50 1.21, 6.03, 15.42 lg/mL air
Aedes aegypti (adult)
Moon et al. (2006)
11 essential oils from
5.44–8.83 lg/mgChaiyasit et al. (2006)
Coptotermes formosanus (termite)
MICs 64 lg/mLPyun and Shin (2006)
10 mg/g LC50 2.6 mg/gCheng et al. (2007)
Aedes aegypti (larvae) LC50 33.45 ppm
LC99 83.39 ppm
10 % solution (repellency)
Champakaew et al. (2007)
18 essential oils
Tawatsin et al. (2006)
IC50 17, 12 lg/mL
Tabanca et al. (2006)
with or without CAB bacteriocin
(in vitro activity )
(Oregano and Savory activity
in pork meat w or w/o CAB)
Oregano, Thyme thymol,
Tea tree, Thyme geraniol
with heat and salt (in foot bath)
1.83, 0.37, 0.06 mM
0.80, 0.17, 0.06 mM
2.50, 0.52, 0.06 mM
5 lL/well diffusion assay
IZ 8–25 mm
In pork meat:
Fabian et al. (2006)
Listeria monocytogenes M
Escherichia coli 10536
Ghalfi et al. (2007)
MFC to kill 99.99%Inouye et al. (2007)
2, 4, 8, 16 lL/disc
30 lg Nitrofurantoin
per mL agar plate)
IZ 15–53 mm
IZ 0–24 mm
Rafii and Shahverdi (2007)
(continued on next page)
complete formula or isolated components, were considered
(see Table 3).
However, some exceptions should be noted. For exam-
ple, the test with Artemisia dracunculus essential oil was
positive in rec-Bacillus subtilis (Zani et al., 1991). Mentha
spicata essential oil was genotoxic in the Drosophila mela-
(SMART) (Franzios et al., 1997; Karpouhtsis et al.,
1998). Anethum graveolens essential oil gave also positive
results in the Drosophila melanogaster SMART assay, in
the sister chromatid exchange (SCE) test and the chromo-
somal aberration (CA) test on human lymphocytes (Laz-
utka et al., 2001). Essential oils extracted from Pinus
sylvestris and Mentha piperita (= Mentha · piperita) were
also genotoxic in the SMART assay and on CA in lympho-
cytes (Lazutka et al., 2001). Concerning isolated constitu-
Table 2 (continued)
EOs or componentsOrganismsConcentrationsReferences
EC50 41.4 lL/L
MIC 1000 lL/L EC50 203.4 lL/L
MIC 750 lL/L EC50 211.0 lL/L
MIC 750 lL/L EC50 188.1 lL/L
MIC 250 lL/L EC50 121.8 lL/L
1% wt/vol in 2 or 20% wt/vol CaC12
solution on Alginate-based Films
Farzaneh et al. (2006)
Tea tree oil
(in QRD 400: emulsifiable
concentrate at 25% active oil)
(in Bologna and ham slices)
(greenhouse insect pests)
Enshaieh et al. (2007)
Oussalah et al. (2007)
4.0, 11.3, 18.9 mL/946 mL
0.3, 0.6, 1.0 mL/60 mL
Cloyd and Chiasson (2007)
0.3, 3.0, 30.0 lM Tabanca et al. (2007)
Tea tree oil
MIC 0.008–0.25 % v/v
MIC 0.03 to >16 mg/L
LC50 0.096, 0.31, 0.29 lg/mL
LC50 0.24, 1.21, 0.31 lg/mL
LC50 0.005, 0.051, 0.041 lg/mL
MIC 8.7–52.4–131.0 lL/L air
MIC 26.2–87.3–175.0 lL/L air
MIC 4.4–34.9–175.0 lL/L air
Van de Sande et al. (2007)
Aedes aegypti (adult)
Dolan et al. (2007)
Lopez et al. (2007)
MIC > 4% v/v
MIC > 4% v/v
MIC 0.125, 0.5, 2.0% v/v
MIC 0.03, 0.06, 0.125% v/v
MIC > 4% v/v
MIC 0.06, 0.125, 0.25% v/v
Fisher et al. (2007)
Van Tol et al. (2007)
MIC: minimum inhibitory concentration, LC: lethal concentration, LD: lethal dose, EC: effective concentration, IC: inhibitory concentration, VC:
virucidal concentration, CC: cytotoxic concentration, IZ: inhibition zone, MNTC: minimum nontoxic concentration, MFC: minimum fungicidal con-
centration, MLC: minimal lethal concentration, LT: lethal time.
ents from essential oils, several monoterpenes and alkenyl-
benzenes were studied. For example, mentone of the pepper
mentha essential oil gave positive results in the Ames test
(Andersen and Jensen, 1984) Mentone was also found
genotoxic in SMART test (Franzios et al., 1997). Anethol
from fennel and anise essential oils was active in the Ames
test (Nestman and Lee, 1983; Hasheminejad and Caldwell,
1994), however, according to Gorelick (1995), it was not,
although it was active in the mouse lymphoma assay
(MLA). Asarone from Acorus calamus essential oil was
found mutagenic in the Ames test (Goggelmann and
Schimmer, 1983) and in hepatocytes (Hasheminejad and
Caldwell, 1994); it induced SCE in human lymphocytes
and in mouse bone marrow (Abel, 1987; Morales-Ramirez
et al., 1992). The oxidized metabolic intermediates of these
two molecules, trans-anethole oxide and trans-asarone
oxide, were genotoxic in the Ames test and induced liver
and skin cancers (Kim et al., 1999). Terpineol was found
active in the Ames test (Gomes-Carneiro et al., 1998). Cin-
namaldehyde, carvacrol, thymol and carvone exerted weak
mutagenic effects in the Ames test (Stammati et al., 1999).
Eugenol was found genotoxic by inducing CA and endore-
duplications in V79 cells (Maralhas et al., 2006).
3.4. Cytoplasmic mutagenicity
Most of the mutagenicity (and anti-mutagenicity) stud-
ies on essential oils were performed on bacteria (Salmonella
typhimurium with Ames test, Escherichia coli with SOS
Chromotest, Bacillus subtilis with DNA Repair test) or
mammalian cells (MLA, human lymphocytes and hepato-
cytes) or on insect (Drosophila melanogaster SMART
assay). In these test systems it is impossible to distinguish
the mode of action of essential oils and their targets. Usu-
ally, cytotoxicity, mutagenicity or anti-mutagenicity are
assessed without being able to take into account possible
Examples of essential oils devoid of mutagenicity
Essential oils or componentsOrganisms References
Cinamylic alcohol, Eugenol,
Methyl eugenol, Isoeugenol,
Anthemis nobilis, Salvia officinalis,
Salvia sclarea, Satureja hortensis,
Satureja montana, Thymus capitatus,
Thymus · citriodorus, Thymus vulgaris,
Camphor, 1,8-Cineole, Citral,
Citronellal, Menthol, b-Myrcene,
a-Terpinene, a-Pinene, a-Bisabolol
Salvia officinalis, Thujone,
1,8-Cineole, Camphor, Limonene
Sekizawa and Shibamoto (1982)
Andersen and Jensen (1984)
Zani et al. (1991)
Gomes-Carneiro et al. (1998, 2005)
Salmonella typhimurium, Escherichia coli
Ipek et al. (2005)
Evandri et al. (2005)
Vukovic-Gacic et al. (2006)
Satureja thymbra, Mentha pulegium
(sub-fractions and constituents)
Bakkali et al. (2005)
Bakkali et al. (unpublished)
Franzios et al. (1997)
Idaomar et al. (2002)
Karpouhtsis et al. (1998)
Mezzoug et al. (2007)
V79 (chrom. aberrations)Muller et al. (1994)
defects in energy metabolism and respiration as direct or
indirect causes. In this respect, tests in yeast (Saccharomy-
ces cerevisiae) have been shown to be potentially very use-
ful. As a facultative anaerobic organism, yeast can survive
with damaged mitochondria and even without mitochon-
dria, and detrimental effects on the respiratory system
can be tested without directly affecting cell survival. This
is in contrast to what can be observed in bacteria and mam-
malian cells where the induction of defects in the respira-
tory system is usually directly associated with cell death.
Taking advantage of the yeast system, it is possible to show
that, among others, mitochondria are very important cellu-
lar targets for essential oils. Indeed, a relation between the
deterioration of mitochondria and immediate changes of
respiratory metabolism was demonstrated after treatment
of yeast cells (Saccharomyces cerevisiae) with the tea tree
essential oil (Schmolz et al., 1999). Cells of Saccharomyces
cerevisiae showed a delay in ethanol production in the pres-
ence of cinnamon, clove, garlic, onion, oregano and thyme
essential oils, as estimated by the measure of the CO2vol-
ume produced (Conner et al., 1984). In plants, the mito-
chondria could not perform oxidative metabolism in the
presence of a-pine `ne (Abrahim et al., 2003).
Moreover, it has been shown that exposure to essential
oils could induce mitochondrial damage involving mito-
chondrial membranes and DNA leading to the formation
of this induction depended, as cytotoxicity, on the composi-
tion of essential oils. Cells in logarithmic growth phase
(budding cells) were also more sensitive to the induction of
cytoplasmic petite mutants. Absence of the formation of
sectored colonies indicated that essential oils damage the
whole mitochondria and mitochondrial DNA of the mother
cells which are immediately converted into respiratory defi-
cient rho0cells characterized by mitochondrial dysfunction
and loss of mitochondrial DNA (Bakkali et al., 2005).
3.5. Carcinogenicity of the essential oils
Since most essential oils have been found to be cytotoxic
without being mutagenic, it is likely that most of them are
also devoid of carcinogenicity. However, some essential
oils or rather some of their constituents may be considered
as secondary carcinogens after metabolic activation (Guba,
2001). For example, essential oils like those from Salvia scl-
area and Melaleuca quinquenervia provoke estrogen secre-
tions which can induce estrogen-dependent cancers. Some
others contain photosensitizing molecules like flavins,
cyanin, porphyrins, hydrocarbures which can cause skin
erythema or cancer. Psoralen, a photosensitizing molecule
found in some essential oils, for instance from Citrus berg-
amia (= Citrus aurantium ssp. bergamia), can induce skin
cancer after formation of covalent DNA adducts under
ultraviolet A or solar light (Averbeck et al., 1990; Averbeck
and Averbeck, 1998). Pulegone, a component of essential
oils from many mint species, can induce carcinogenesis
through metabolism generating the glutathione depletory
p-cresol (Zhou et al., 2004). Safrole, the major constituent
of Sassafras albidum and Ocotea pretiosa (= Mespilo-
daphne pretiosa) essential oils, induces carcinogenic metab-
olites in rodents (Miller et al., 1983; Burkey et al., 2000; Liu
et al., 2000). Methyleugenol from Laurus nobilis and Mel-
aleuca leucadendron essential oils has also been shown to
be carcinogenic in rodents (Burkey et al., 2000). D-Limo-
nene, a monoterpene found in Citrus essential oil, was car-
cinogenic in male rats, by a male-rat specific mechanism
(NTP, 1990). Estragole, a constituent of Ocimum basilicum
and Artemisia dracunculus essential oils, has shown carcin-
ogenic properties in rat and mouse (Miller et al., 1983;
Anthony et al., 1987).
3.6. Antimutagenic properties of essential oils
Until now, most studies indicated that anti-mutagenic
properties may be due to inhibition of penetration of the
mutagens into the cells (Kada and Shimoi, 1987; Shankel
et al., 1993), inactivation of the mutagens by direct scaveng-
ing, antioxidant capture of radicals produced by a mutagen
or activation of cell antioxidant enzymes (Hartman and
Shankel, 1990; Sharma et al., 2001; Ipek et al., 2005), inhi-
bition of metabolic conversion by P450 of promutagens into
mutagens (Ramel et al., 1986; De Flora and Ramel, 1988;
Kuo et al., 1992; Waters et al., 1996; Gomes-Carneiro
et al., 2005), or activation of enzymatic detoxification of
mutagens for instance by plant extracts. Less known is a
possible antimutagenic interference with DNA repair sys-
tems after induction of genotoxic lesions. Some antimuta-
genic agents can either inhibit error-prone DNA repair or
promote error-free DNA repair (Kada and Shimoi, 1987;
Kuroda and Inoue, 1988; De Flora et al., 1985, 1992a,b;
Bronzetti et al., 1992; Vukovic-Gacic et al., 2006).
The biochemistry of anti-mutagenic interference with
promutagen metabolism to prevent mutagenesis is known
and relatively well documented, as well as, during recent
years, the role and reactions of ROS scavengers, such as
glutathione, superoxide dismutase, catalase, N-acetylcy-
stein, provitamins like retinoids, carotenoids and tocophe-
rols, flavonoids and other polyphenols, etc. (Odin, 1997;
De Flora et al., 1999). However, since the work of Kada
and Shimoi (1987) and Kuroda and Inoue (1988) on Esch-
erichia coli, nobody has examined in more detail this type
of antimutagenicity possibly involving interference with
DNA repair via intracellular prooxidant reactions of the
latter compounds or terpenic and phenolic compounds
from aromatic plants.
Kuo et al. (1992) found that the natural compounds,
tannic acid and apigenine, reduced the frequency of SCEs
induced by nitropyrenes in CHO cells. Hernandez-Ceruelos
et al. (2002) showed that Matricaria chamomilla essential
oil inhibits SCEs induced by daunorubicine and methyl
methane sulfonate in mouse bone marrow cells. Gomes-
Carneiro et al. (2005) showed by Ames test that a-bisabolol
benzo-a-pyrene and 2-aminofluorene induced-mutagenesis,
but less so for 4-nitroquinoline-N-oxide and 2-nitrofluo-
rene induced-mutagenesis and not at all for sodium azide
and nitro-o-phenylenediamine induced-mutagenesis; this
antimutagenic effect is due to a-bisabolol interaction with
promutagen biotransformation enzymes or to inhibition
of hepatic mono-oxygenases acting on P450 cytochromes.
The same authors showed also in the Wistar rat inhibitor
effects on CYP2B1 responsible for the metabolism of cyclo-
phosphamide into teratogenic precursors (Gomes-Carneiro
et al., 2003). Evandri et al. (2005) showed by Ames test and
Escherichia coli uvrA that Melaleuca alternifolia and Lav-
andula angustifolia essential oils strongly inhibit 2-nitroflu-
orene induced-mutagenesis. Vukovic-Gacic et al. (2006)
showed that Salvia officinalis and major components
thuyone, 1,8-cineole, camphor
UVC-induced mutagenesis in Salmonella typhimurium,
Escherichia coli and Saccharomyces cerevisiae. De-Oliveira
et al. (1997, 1999) have demonstrated that (?)-menthol,
(?)-a-pinene, (+)-a-pinene, a-terpinene, a-terpineol, 1,8-
cineole, d-limonene, camphor, citronellal and citral modu-
late hepatic mono-oxygenase activity such as CYP1A1 and
CYP2B1 interacting with promutagen or procarcinogen
xenobiotic biotransformation. Idaomar et al. (2002) have
found by SMART test that Helichrysum italicum, Ledum
groenlandicum (= Rhododendron groenlandicum) and Rav-
ensara aromatica (= Cinnamomum camphora) essential oils
and their mixture reduce the urethane-induced mutation
frequency in Drosophila melanogaster. In a more recent
study, they showed in the same system that Origanum com-
pactum essential oil and some of its sub-fractions and con-
stituents are antimutagenic against the indirect-acting
mutagen urethane and also against the direct-acting muta-
gen methyl methanesulfonate (Mezzoug et al., 2007).
It is now accepted that prooxidant activities can induce
late apoptosis and necrosis (Schwartz, 1996; Sakagami
et al., 1999; Hadi et al., 2000). Prooxidant activities may
damage cellular membranes, in particular those of mito-
chondria, and thus promote the release of Ca++, cyto-
chrome C and ROS. This leads to cell death, at least in
mammalian cells, whereas yeast cells are able to survive
in spite of mitochondrial damage (Bakkali et al., 2005,
2006; Averbeck et al., 1990).
It has been recently demonstrated in the yeast Saccharo-
myces cerevisiae that induction of mitochondrial damage
transforming Rho+cells into rho0cells and the induction
of apoptosis/necrosis by a combined exposure to essential
oils and nuclear mutagens caused a striking reduction of
the frequency of nuclear genetic events. Typical mutagenic
agents were used such as ultraviolet C (UVC) radiation
which forms pyrimidine dimers and 6-4 photoproducts, 8-
methoxypsoralen (8-MOP) activated by ultraviolet A
(UVA) radiation which forms DNA mono- and biadducts,
or methyl methanesulfonate (MMS) which methylates
DNA bases. The reduction in mutant frequency in the pres-
ence of essential oils was accompanied by a strong synergis-
tic induction of cytoplasmic ‘‘petite’’ mutants (Bakkali
et al., 2006).
and limonene inhibit
The anti-mutagenic effect was independent of the type of
mutations, i.e. reversion, intra- or intergenic recombina-
tion. The extent of this anti-mutagenic effect depended on
the mutagen and oil concentrations. However, unexpect-
edly, the mechanism of the decrease of mutagenicity did
not depend on the type of essential oil but on the type of
mutagen, thus on the type of lesions and consequently on
the DNA repair or lesion avoidance system involved.
In fact, after combined treatment by UVC or 8-MOP/
UVA plus essential oils, the transformation of Rho+cells
into rho0cells resulted in a decrease of the frequency of
mutants accompanied by a slight resistance of the survival
(Brun et al., 2003; Bakkali et al., 2006). After UVC or
8-MOP/UVA alone, less mutants were also found in a
rho0mutant, i.e. a complete BET-induced rho0selected
by the alcaloid lycorine, than in the wild type Rho+. In that
case, the reduction in mutation frequency was the same as
that after the combined treatments confirming the impor-
tance of mitochondrial dysfunction for these effects (Bak-
kali et al., 2006).
The same decrease of mutant frequencies was also found
in a nucleotide excision repair (NER) defective rad3
mutant after UVC/essential oil combined treatment. Thus,
the error-free NER repair system does not play any role in
this decrease and probably not the error-free homologous
recombination in the case of 8-MOP/UVA. It seems that
translational synthesis involving an error-free polymerase
is favoured by the energy deficit in rho0cells rather than
true DNA repair that would much more lead to higher cell
survival and rely on repair enzymes highly dependent on
ATP and energy supply.
Concerning the combined treatment MMS/essential
oils, there was a slight decrease of the mutant frequencies
but a strong additional decrease of the survival by the
essential oils. However, as a function of survival, this addi-
tional cytotoxicity caused a notable reduction of the
mutant frequencies for a same survival level. The decrease
of cell survival was also accompanied by a synergistic
increase of cytoplasmic petite mutants. Thus, in this case,
the essential oils contributed to the elimination of the cells
already affected by MMS, leading potential mutants to
death by late apoptosis and necrosis (Bakkali et al., 2006).
The reduction by essential oils of the frequency of muta-
tions induced by the mutagens was always accompanied by
a synergistic induction of complete petite mutants. More-
over, essential oils alone or in combined treatments mainly
induced necrosis rather than apoptosis. This corroborates
with the fact that petite mutants were true rho0mutants
unable to perform apoptosis but only able to passively
undergo necrosis, since functional mitochondria are neces-
sary to induce apoptosis (Van Houten et al., 2006).
4. Underlying mechanisms: mitochondrial damage and
prooxidant cytotoxic effects
Several studies have demonstrated that complex natural
nutrients like vegetables, fruits, herbs and spices contain
numerous antioxidant molecules such as carotenoids, reti-
noids, tocopherols, ascorbic acid, phenolic acids, flavo-
noids and polyphenols (Chu et al., 2000; Vinson et al.,
2001; Luximon-Ramma et al., 2002; Cheung et al., 2003;
Wu et al., 2004; Shyamala et al., 2005; Grassmann, 2005;
Soobrattee et al., 2005; Saura-Calixto and Goni, 2006).
Essential oils also include antioxidants such as terpenoid
and phenolic components. The antioxidant property of
essential oils and components has been very often verified
in vitro by physical–chemical methods (Ruberto and Barat-
ta, 2000; Pizzale et al., 2002; Candan et al., 2003; Alma
et al., 2003; Kulisic et al., 2004; Tepe et al., 2004a; Mimi-
ca-Dukic et al., 2004; Sacchetti et al., 2005; Tuberoso
et al., 2005; Singh et al., 2006; Basile et al., 2006; Trevisan
et al., 2006; Bozin et al., 2006). In particular, the antioxi-
dant capacity of some phenolic compounds has been
invoked to promote their use as natural food additives
(Aeschbach et al., 1994).
For example, some essential oils showing different levels
of cytotoxicity exhibited different antioxidative capacities
depending on the composition of the oil and especially
on their phenolic content (Bakkali, data not shown). This
raised the obvious question how such antioxidants,
although non-mutagenic, could be cytotoxic.
In eukaryotes, mitochondria produce superoxide anions
and hydrogen peroxide which react with their iron content
to generate reactive intermediates like hydroxyl radical
which is highly damaging to mitochondrial DNA. Dam-
aged mitochondrial DNA inhibits the expression of elec-
tron transport proteins leading to the accumulation of
ROS (Van Houten et al., 2006). In line with this, the fol-
lowing reaction mechanism for essential oils can be envis-
aged: essential oils by penetrating through the cell wall
and cytoplasmic membrane disrupt and permeabilize them
and especially damage mitochondrial membranes. The
mitochondria, by changes in electron flow through the elec-
tron transport chain, produce free radicals which oxidize
and damage lipids, proteins and DNA. Moreover, some
phenolic components of essential oils are oxidized by con-
tact with ROS producing very reactive phenoxyl radicals
which add to the ROS released by mitochondria. These
types of radical reactions are dependent on and enhanced
by the presence of cell transition metal ions such as
Fe++, Cu++, Zn++, Mg++or Mn++(Stadler et al., 1995;
Cao et al., 1997; Sakihama et al., 2002; Jimenez Del Rio
and Velez-Pardo, 2004; Azmi et al., 2006).
These reactions were demonstrated in the yeast Saccha-
romyces cerevisiae by employing antioxidants like glutathi-
one and catalase, and the iron chelator deferoxamine
(inhibiting the Fenton reaction) which lowered the cytotox-
icity of tested essential oils depending on the two types of
agents and the oil (Bakkali et al., 2005). Protective effects
by antioxidants like N-acetyl-cysteine, glutathione or Trol-
ox were also observed on eugenol- or essential oil-induced
DNA fragmentation, cytotoxicity or apoptosis (Fujisawa
et al., 2002; Yoo et al., 2005; Paik et al., 2005; Wu et al.,
The origin and site of prooxidation phenomena in cells
seem controversial. In the work of Galati et al. (2002) on
prooxidant activity of phenoxyl radicals of polyphenolics,
phenol ring-containing phenolic compound oxidation
appears to take place in the cytosol by contact with per-
oxidase/H2O2to form phenoxyl radical which may coox-
idize glutathione (GSH) forming thiol radical; the latter
react with GSH giving rise to disulfide radical anion
which reduces O2 to form superoxide anion RSO? or
RSOO? and GSSG. In the work of Sakihama et al.
(2002) on plant phenolic prooxidant activity mediated
by metals, in the presence of O2, transition Cu++and
Fe++metal ions catalyze the oxidation of phenol ring
forming phenoxyl radical leading to the formation of
ROS and hydroxyl radical. However, according to Galati
and O’Brien (2004), this metal ion-mediated redox cycling
concerns the catechol ring which is initially oxidized by
Cu++and generates a semiquinone radical that reacts
with O2to form superoxide anion; the latter oxidizes cat-
echol and forms again a semiquinone radical plus H2O2
which is converted by Cu++into hydroxyl radical in a
Fenton-like reaction. Anyhow, for both authors, phe-
noxyl, thiyl and hydroxyl radicals and ROS then damage
mitochondria involving collapse of the membrane poten-
tial (Galati and O’Brien, 2004). This scheme seems to be
supported also by Fujisawa et al. (2002) and Yoo et al.
On the contrary, according to Yoon et al. (2000),
Morin et al. (2001), Burt (2004) and Van Houten et al.
(2006), it can be inferred that lipophilic phenolic com-
pounds themselves permeabilize the mitochondrial mem-
branes where transition metal ions Fe++and Cu++are
sequestered in the intermembrane space (Yang et al.,
2005; Mehta et al., 2006), and provoke a leakage of these
ions and ROS from mitochondria which also contain
GSH (Hansen et al., 2006). This context suggests that
phenolic compounds are oxidized during permeabilization
and leakage giving rise to phenoxyl (or semiquinone) rad-
icals which continue prooxidant chain reactions as above
and with proteins and DNA, and generate new ROS. In
other words, mitochondrial membranes are first damaged
by permeabilization resulting in a prooxidant status there-
after. This is supported by the results obtained on the
induction of petite mutants in yeast after treatment by
GSH and catalase antioxydants and the iron chelating
agent deferoxamine and essential oils. The frequency of
petite mutants did not decrease (data not shown) with
increasing survival in the presence of these agents (Bakka-
li et al., 2005). This is in line with the fact that prooxidant
reactions are initiated at the mitochondrial level and anti-
oxydants or the Fenton reaction inhibitor protect the cells
against oxygen radical mediated reactions from permeabi-
lized mitochondria thus increasing survival. In case of
prooxidant reactions occurring in the cytosol, antioxi-
dants would also have protected the mitochondria leading
to decreased frequency of petite mutants associated with
Moreover, the fact that in yeast (Saccharomyces cerevi-
siae) induction of repair DNA genes by essential oils (Bak-
kali et al., 2005) was relatively weak but significant in
comparison to the rather strong induction observed by true
nuclear mutagens like ultraviolet C or 8-methoxypsoralen
plus ultraviolet A (Averbeck and Averbeck, 1994, 1998)
or methyl methanesulfonate (Bakkali et al., 2005), which
induce intrastrand, interstrand crosslinks and double
strand breaks or base methylations, respectively, and that
the essential oils were not mutagenic clearly shows that
the nuclear DNA lesions induced arose through reactive
species such as phenoxyl, thiyl, hydroxyl, peroxyl and
superoxide radicals which rather induce base modifications
and single strand breaks which are repairable without giv-
ing rise to significant nuclear mutagenic effects. Further-
more, the tested essential oils induced cytoplasmic petite
mutants which indicates dysfunction or absence of mito-
chondria (Bakkali et al., 2005).
Several studies have shown antioxidant properties
in vitro of many natural products including essential oils.
From this, it was inferred that they could be beneficial
for human health in line with recent findings and common
belief that many diseases are due to an overload of oxida-
tive stress reactions following excessive consumption of fat,
sugar, meat, etc. Antioxidants are believed to be directly
antimutagenic (Clark, 2002) and anticarcinogenic due to
their radical scavenging properties (Ames et al., 1993; Birt
et al., 2001; Surh, 2002; Ferguson et al., 2004; Collins,
However, some compounds of natural products like
vitamins A, C, E, flavonoids, polyphenolics or especially
phenolic components which show antioxidant capacities
in silico, can be, after penetrating cells, oxidized by
ROS and thus generate additional radical species like phe-
noxyl, hydroxyl and superoxide radicals and hydrogen
peroxide (Schwartz et al., 1993; Albanes et al., 1995;
Schwartz, 1996; Sakagami and Satoh, 1997; Bijur et al.,
1997; Young and Lowe, 2001; Lowe et al., 2003). Indeed,
antioxidants by interacting with ROS are converted into
prooxidants which are able to oxidize lipids, proteins
and DNA (Metodiewa et al., 1999; Cowan, 1999; Galati
et al., 2002; Galati and O’Brien, 2004; Fujisawa et al.,
2002; Sakihama et al., 2002; Nemeikaite-Ceniene et al.,
2005; Barbehenn et al., 2005; Atsumi et al., 2005). Appar-
ently, the intracellular defenses based on glutathione
peroxidase, glutathione reductase, catalase, superoxide
dismutase, are insufficient to inhibit these prooxidant
reactions, and the natural antioxidant cellular defenses
can be overwhelmed. Volatil terpenic and phenolic com-
ponents of essential oils can function as prooxidants by
affecting the cellular redox status. This may lead to late
apoptosis and/or necrosis including damage to proteins
and DNA and overall cytotoxic effects (Bakkali et al.,
Nevertheless, prooxidant effects may depend on the
concentration of natural extracellular antioxidant com-
pounds, such as gallic acid from tannin or some ascorbic
acid derivatives, which penetrated the cells (Sakagami
et al., 1999). In fact, assuming that the major source of
oxidation is of mitochondrial origin, if the antioxidant
concentration is too weak to permeabilize mitochondrial
membranes, conversion into prooxidant may not occur,
and the antioxidant would keep its activity and act as
such. This could explain the results reported by Aydin
et al. (2005), who noticed that non-cytotoxic low concen-
trations of thymol, carvacrol and c-terpinene protected
against DNA strand breakage induced by semiquinone
and oxygen radicals formed by 2-amino-3-methylimi-
dazo(4,5-f)-quinoline (IQ) and mitomycin C (MMC) in
DNA damage. Fan and Lou (2004) found that some poly-
phenols were good antioxidants at low concentration but,
at higher concentration, they induced cellular DNA dam-
age. Also, at low concentrations, retinol and tocopherol
showed antioxidant and antimutagenic activities, whereas,
at high concentration, they became themselves genotoxic
(Bronzetti et al., 2001). Palozza et al. (2004) observed also
inhibition or enhancement of apoptosis depending on
carotenoid concentration. Ramassamy (2006) reported
greater neuroprotective effects by green tea, curcumin
and ginkgo biloba extracts at small doses than at high
doses. Vitamin E has prooxidant effects at high concentra-
tions (Foti and Ingold, 2003). In such cases, low concen-
trations could not damage mitochondria, the antioxidant
was not oxidized and could scavenge radicals. In contrast,
high concentration could damage and permeabilize mito-
chondria, the antioxidant was oxidized and could react
as prooxidant damaging DNA and proteins. It seems that
the switch from anti- to prooxidant reactions occurs at low
antioxidant concentrations in a very narrow range (Bol-
ton, 2002). This concentration-dependent effect is in
favour of the notion that mitochondrial membranes may
be the target and their permeabilization the primary event
to convert antioxidants into prooxidants.
In contrast to the established notion that the antioxidant
properties of natural compounds such as fruit and vegeta-
ble polyphenols or herb and essential oil phenols and terp-
enes determine their protective effect against mutagens
(Diplock et al., 1998; Weisburger, 1999; Chu et al., 2000;
Clark, 2002; Wu et al., 2004; Collins, 2005; Skerget et al.,
2005; Grassmann, 2005; Romero-Jimenez et al., 2005;
Saura-Calixto and Goni, 2006), it has become clear that
also the prooxidant properties of these compounds can
play a significant ‘‘protective’’ role by removing damaged
cells by apoptosis (Sakagami et al., 1999; Hadi et al.,
2000; Liu et al., 2001; Sun et al., 2005a; Vukovic-Gacic
et al., 2006; Bakkali et al., 2006). An interesting new aspect
of antioxidants would be their possible prooxidant activity
in cells (Martin, 2006). In the latter case, protection is quite
indirect since it involves mitochondrial damage which
either reduces by lack of energy the cell capacity to perform
an error-prone repair and to mutate (Bakkali et al., 2006),
or produces apoptosis and necrosis, thus eliminating
In cells, the redox balance is very sensitive. Probably,
compounds showing antioxidant activity can reduce the
main load of oxidative stress but when there is an imbal-
ance between oxidizing and reducing equivalents where
the former predominates (Sies and Cadenas, 1985), for
example when the antioxidant is oxidized and thus con-
verted into a prooxidant, the antioxidant cellular defenses
cannot fully keep up with the oxidative stress and impor-
tant cellular constituents are damaged. From results of
the literature on polyphenolic and phenolic compounds,
it can be inferred that essential oils can act mainly as pro-
oxidants by intermediate of their volatile constituents like
phenolic constituents, terpenes or terpenoids, which turn
themselves into prooxidants (Sakagami et al., 1999; Saki-
hama et al., 2002; Fujisawa et al., 2002; Barbehenn et al.,
2005; Bakkali et al., 2006).
Thus, the fact that, in silico, some compounds behave
like antioxidants does not at all predict their biological
effects in living cells. For example, Origanum compactum
essential oil was characterized by a high antioxidant activ-
ity in silico and a prooxidant activity in vitro due to the
presence of phenolic components which confer high cyto-
toxicity to whole cells and damage to mitochondria associ-
ated with antimutagenicactivity.
Helichrysum italicum essential oil, which possessed a good
antioxidant activity in silico, did not show any cytotoxic
effects, induced no cytoplasmic petite mutants and was
not antimutagenic, probably because it did not affect mito-
chondria and thus exhibited no prooxidant activity. Arte-
misia herba-alba and Cinnamomum camphora essential
oils showed a very weak antioxidant activity in silico, how-
ever, they were cytotoxic, they induced many cytoplasmic
petite mutants and showed a high antimutagenic effect
probably due to prooxidant activity (Bakkali, unpublished
data; Bakkali et al., 2005, 2006).
On the contrary,
5. Specificity of essential oils
The question of specificity of the different essential oils
also arises. Very few studies have analyzed enough essen-
tial oils and biological endpoints to determine whether
there is a specificity for different effects according to dif-
ferent oils or not. Clearly, it has been shown by Bakkali
et al. (2005, 2006) that the tested essential oils presented
a specificity in the amplitude, but not in the mode of
action, of the biological effects, i.e. cytotoxicity, cytoplas-
mic mutant induction, gene induction and antigenotoxic
effects. However, they did exhibit a specificity of the mode
of action concerning production of ROS, probably due to
differences in their actual composition corresponding to
differences in compartmentation of the oxidative stress
(Hansen et al., 2006). Concerning antigenotoxicity, the
tested essential oils showed the same protective activity.
However, the mode of protection differed, not according
to the type of oil, but according to the mutagens, i.e. to
the type of lesions induced and thus, to the type of their
enzymatic recognition and processing leading to transla-
tional synthesis or late apoptosis/necrosis (Bakkali et al.,
6. Synergism between the components of essential oils
Regarding their biological properties, it has to be kept
in mind that essential oils are complex mixtures of numer-
ous molecules, and one might wonder if their biological
effects are the result of a synergism of all molecules or
reflect only those of the main molecules present at the
highest levels according to gas chromatographical analysis.
In the literature in most cases, only the main constituents
of certain essential oils like terpineol, eugenol, thymol,
carvacrol, carvone, geraniol, linalool, citronellol, nerol,
analyzed. Generally, the major components are found to
reflect quite well the biophysical and biological features
of the essential oils from which they were isolated (Ipek
et al., 2005), the amplitude of their effects being just
dependent on their concentration when they were tested
alone or comprised in essential oils. Thus, synergistic func-
tions of the various molecules contained in an essential oil,
in comparison to the action of one or two main compo-
nents of the oil, seems questionable. However, it is possi-
ble that the activity of the main components is modulated
by other minor molecules (Franzios et al., 1997; Santana-
Rios et al., 2001; Hoet et al., 2006). Moreover, it is likely
that several components of the essential oils play a role in
defining the fragrance, the density, the texture, the colour
and above all, cell penetration (Cal, 2006), lipophilic or
hydrophilic attraction and fixation on cell walls and mem-
branes, and cellular distribution. This last feature is very
important because the distribution of the oil in the cell
determines the different types of radical reactions pro-
duced, depending on their compartmentation in the cell.
In that sense, for biological purposes, it is more informa-
tive to study an entire oil rather than some of its compo-
nents because the concept of synergism appears to be more
7. Medicinal and future medical applications
The cytotoxic capacity of the essential oils based on a
prooxidant activity can make them excellent antiseptic
and antimicrobial agents for personal use, i.e. for purifying
air, personal hygiene, or even internal use via oral con-
sumption, and for insecticidal use for the preservation of
crops or food stocks.
A big advantage of essential oils is the fact that they are
usually devoid of long-term genotoxic risks. Moreover,
some of them show a very clear antimutagenic capacity
which could well be linked to an anticarcinogenic activity.
Recent studies have demonstrated that the prooxidant
activity of essential oils or some of their constituents, as
also that of some polyphenols, is very efficient in reducing
local tumor volume or tumor cell proliferation by apoptotic
and/or necrotic effects (Schwartz, 1996; Zheng et al., 1997;
Ohizumi et al., 1997; Crowell, 1999; Buhagiar et al., 1999;
Legault et al., 2003; Hata et al., 2003; Salim and Fukushi-
ma, 2003; Mazie `res et al., 2003, 2004; Carvalho de Sousa
et al., 2004; Carnesecchi et al., 2004; Chen et al., 2004; Shen
et al., 2004; Kloog and Cox, 2004; Paik et al., 2005;
Yoo et al., 2005; Dudai et al., 2005; Tsuneki et al., 2005;
Manosroi et al., 2006; Sylvestre et al., 2005, 2006; Wu
et al., 2006; Kachadourian and Day, 2006). Sylvestre
et al. (2005, 2006) have shown that Myrica gale essential
oil has an anticancerogenic activity on the lung and colon
cancer cell lines. Salim and Fukushima (2003) have shown
an antiproliferative activity and inhibition of 1,2-dimethyl-
hydrazine-induced cancer in the rat by Nigella sativa.
Manosroi et al. (2006) have shown an inhibition of the pro-
liferation of murine leukemia and human mouth epidermal
carcinoma cell lines by Ocimum sanctum, Citrus citratus,
Alpinia officinarum, Lavandula angustifolia, Vetiveria ziza-
nioides, Zingiber montanum, Piper nigrum, Cymbopogon
nardus, Curcuma longa, Ocimum basilicum, Citrus hystrix,
Piper betle, Albizia lebbeck, Ocimum americanum, Mentha
spicata and Psidium guajava essential oils. Yoo et al.
(2005) demonstrated that eugenol from Eugenia caryophyl-
lata (= Syzygium aromaticum) inhibits the proliferation of
cancerous cells. Geraniol inhibits also colon cancer cell
proliferation by inducing membrane depolarisation and
interfering with ionic canals and signalling pathways. Car-
nesecchi et al. (2004) have also demonstrated that geraniol
inhibits DNA synthesis and reduces the volume of colon
tumours. Mazie `res et al. (2003, 2004) and Kloog and Cox
(2004) showed that farnesyle and geranyl–geranyl inhibit
the post-translational modification necessary to the trans-
formant capacity of the gene ras and thus prevent the
tumour formation. Tsuneki et al. (2005) showed inhibition
of angiogenesis by b-eudesmol from Atractylodes lancea.
Many tumor cells are characterized by severe changes in
energy metabolism, mitochondrial overproduction and per-
manent oxidative stress (Czarnecka et al., 2006). Essential
oils, due to their capacity to interfere with mitochondrial
functions, may add prooxidant effects and thus become
genuine antitumor agents. Many radical producing agents
are in fact used in antitumor treatments. In the case of
essential oils, radical production could be very well con-
trolled and targeted without presenting by itself any toxic
or mutagenic side-effects to healthy tissues. Essential oils
or their active constituents could be included in vectorized
liposomes (Sinico et al., 2005; Lai et al., 2006; Fang et al.,
2006) that would allow to better define the quantities
applied. Thus, essential oils could make their way from
the traditional into the modern medical domain.
The authors are grateful to Dr Dominique Baudoux and
Dr Abdesselam Zhiri from Pranarom International for
their interest on the subject, their precious advices and
helpful discussions. F.B. is indebted to the Agence Univers-
itaire de la Francophonie (AUF) for a post-doctoral
Abel, G., 1987. Chromosomal damaging effect of b-asarone on human
lymphocytes. Planta Med. 53, 251–253.
Abou El Ela, N.E., El-Sahn, A.A., Enan, E.E., 2004. Pediculicidal activity
of certain plant essential oils against head lice Pediculus humanus
capitis. J. Egypt Public Health Assoc. 79, 383–397.
Abrahim, D., Francischini, A.C., Pergo, E.M., Kelmer-Bracht, AM., Ishii-
Iwamoto, E.L., 2003. Effects of a-pinene on the mitochondrial
respiration of maize seedlings. Plant Physiol. Biochem. 41, 985–991.
Aeschbach, R., Loliger, J., Scott, B.C., Murcia, A., Butler, J., Halliwell,
B., Aruoma, O.I., 1994. Antioxidant actions of thymol, carvacrol, 6-
gingerol, zingerone and hydroxytyrosol. Food Chem. Toxicol. 32, 31–
Albanes, D., Heinonen, O.P., Huttunen, J.K., Taylor, P.R., Virtamo, J.,
Edwards, B.K., Haapakoski, J., Rautalahti, M., Hartman, A.M.,
Palmgren, J., et al., 1995. Effects of alpha-tocopherol and beta-
carotene supplements on cancer incidence in the alpha-tocopherol
beta-carotene cancer prevention study. Am. J. Clin. Nutr. 62, 1427S–
Alma, M.H., Mavi, A., Yildirim, A., Digrak, M., Hirata, T., 2003.
Screening chemical composition and in vitro antioxidant and antimi-
crobial activities of the essential oils from Origanum syriacum L.
growing in Turkey. Biol. Pharm. Bull. 26, 1725–1729.
Amer, A., Mehlhorn, H., 2006a. Larvicidal effects of various essential oils
against Aedes, Anopheles, and Culex larvae (Diptera, Culicidae).
Parasitol. Res. 99, 466–472.
Amer, A., Mehlhorn, H., 2006b. Repellency effect of forty-one essential
oils against Aedes, Anopheles, and Culex mosquitoes. Parasitol. Res.
Ames, B.N., Shigenaga, M.K., Hagen, T.M., 1993. Oxidants, antioxi-
dants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci.
USA 90, 7915–7922.
Andersen, P.H., Jensen, N.J., 1984. Mutagenic investigation of pepper-
mint oil in the Salmonella/mammalian microsome test. Mutat. Res.
Angioni, A., Barra, A., Coroneo, V., Dessi, S., Cabras, P., 2006. Chemical
composition, seasonal variability, and antifungal activity of Lavandula
stoechas L. ssp. stoechas essential oils from stem/leaves and flowers. J.
Agric. Food Chem. 54, 4364–4370.
Anthony, A., Caldwell, G., Hutt, A.G., Smith, R.L., 1987. Metabolism of
estragole in rat and mouse and influence of dose size on excretion of
the proximate carcinogen 10-hydroxyestragole. Food Chem. Toxicol.
Armstrong, J.S., 2006. Mitochondrial membrane permeabilization: the
sine qua non for cell death. BioEssays 28, 253–260.
Arnal-Schnebelen, B., Hadji-Minaglou, F., Peroteau, J.F., Ribeyre, F., de
Billerbeck, V.G., 2004. Essential oils in infectious gynaecological
disease: a statistical study of 658 cases. Int. J. Aromather. 14, 192–
Atsumi, T., Murakami, Y., Shibuya, K., Tonosaki, K., Fujisawa, S., 2005.
Induction of cytotoxicity and apoptosis and inhibition of cyclooxy-
genase-2 gene expression, by curcumin and its analog, alpha-diisoeu-
genol. Anticancer Res. 25, 4029–4036.
Averbeck, D., Averbeck, S., Dubertret, L., Young, A.R., Morlie `re, P.,
1990. Genotoxicity of bergapten and bergamot oil in Saccharomyces
cerevisiae. J. Photochem. Photobiol. B 7, 209–229.
Averbeck, D., Averbeck, S., 1994. Induction of the genes RAD54 and
RNR2 by various damaging agents in Saccharomyces cerevisiae.
Mutat. Res. 315, 123–138.
Averbeck, D., Averbeck, S., 1998. DNA photodamage, repair, gene
induction and genotoxicity following exposures to 254 nm UV and 8-
methoxypsoralen plus UVA in a eukaryotic cell system. Photochem.
Photobiol. 68, 289–295.
Aydin, S., Basaran, A.A., Basaran, N., 2005. The effects of thyme volatiles
on the induction of DNA damage by the heterocyclic amine IQ and
mitomycin C. Mutat. Res. 581, 43–53.
Azmi, A.S., Bhat, S.H., Hanif, S., Hadi, S.M., 2006. Plant polyphenols
mobilize endogenous copper in human peripheral lymphocytes leading
to oxidative DNA breakage: a putative mechanism for anticancer
properties. FEBS Lett. 580, 533–538.
Bagamboula, C.F., Uyttendaele, M., Debevere, J., 2004. Inhibitory effect
of thyme and basil essential oils, carvacrol, thymol, estragol, linalool
and p-cymene towards Shigella sonnei and Shigella flexneri. Food
Microbiol. 21, 33–42.
Bakkali, F., Averbeck, S., Averbeck, D., Zhiri, A., Idaomar, M., 2005.
Cytotoxicity and gene induction by some essential oils in the yeast
Saccharomyces cerevisiae. Mutat. Res. 585, 1–13.
Bakkali, F., Averbeck, S., Averbeck, D., Zhiri, A., Baudoux, D., Idaomar,
M., 2006. Antigenotoxic effects of three essential oils in diploid yeast
(Saccharomyces cerevisiae) after treatments with UVC radiation, 8-
MOP plus UVA and MMS. Mutat. Res. 606, 27–38.
Barbehenn, R., Cheek, S., Gasperut, A., Lister, E., Maben, R.,
2005. Phenolic compounds in red oak and sugar maple leaves
have prooxidant activities in the midgut fluids of Malacosoma
disstria and Orgyia leucostigma caterpillars. J. Chem. Ecol. 31,
Basile, A., Senatore, F., Gargano, R., Sorbo, S., Del Pezzo, M., Lavitola,
A., Ritieni, A., Bruno, M., Spatuzzi, D., Rigano, D., Vuotto, M.L.,
2006. Antibacterial and antioxidant activities in Sideritis italica
(Miller) Greuter et Burdet essential oils. J. Ethnopharmacol. 107,
Basilico, M.Z., Basilico, J.C., 1999. Inhibitory effects of some spice
essential oils on Aspergillus ochraceus NRRL 3174 growth and
ochratoxin A production. Lett. Appl. Microbiol. 29, 238–241.
Betts, T.J., 2001. Chemical characterisation of the different types of
volatile oil constituents by various solute retention ratios with the use
of conventional and novel commercial gas chromatographic stationary
phases. J. Chromatogr. A 936, 33–46.
Bhatnagar, M., Kapur, K.K., Jalees, S., Sharma, S.K., 1993. Laboratory
evaluation of insecticidal properties of Ocimum basilicum L. and
Ocimum sanctum L. plants, essential oils and their major constituents
against vector mosquito species. J. Entom. Res. 17, 21–26.
Bijur, G.N., Ariza, M.E., Hitchcock, C.L., Williams, M.V., 1997.
Antimutagenic and promutagenic activity of ascorbic acid during
oxidative stress. Environ. Mol. Mutagen. 30, 339–345.
Birt, D.F., Hendrich, S., Wang, W., 2001. Dietary agents in cancer
prevention: flavonoids and isoflavonoids. Pharmacol. Therap. 90, 157–
Bolton, J.L., 2002. Quinoids, quinoid radicals, and phenoxyl radicals
formed from estrogens and antiestrogens. Toxicology 177, 55–
Botelho, M.A., Nogueira, N.A., Bastos, G.M., Fonseca, S.G., Lemos,
T.L., Matos, F.J., Montenegro, D., Heukelbach, J., Rao, V.S., Brito,
G.A., 2007. Antimicrobial activity of the essential oil from Lippia
sidoides, carvacrol and thymol against oral pathogens. Braz. J. Med.
Biol. Res. 40, 349–356.
Bouchra, C., Achouri, M., Idrissi Hassani, L.M., Hmamouchi, M., 2003.
Chemical composition and antifungal activity of essential oils of seven
Moroccan Labiatae against Botrytis cinerea Pers: Fr. J. Ethnophar-
macol. 89, 165–169.
Bowles, E.J., 2003. Chemistry of Aromatherapeutic Oils. Allen & Unwin,
Bozin, B., Mimica-Dukic, N., Simin, N., Anackov, G., 2006. Character-
ization of the volatile composition of essential oils of some lamiaceae
spices and the antimicrobial and antioxidant activities of the entire
oils. J. Agric. Food Chem. 54, 1822–1828.
Branco, M.R., Marinho, H.S., Cyrne, L., Antunes, F., 2004. Decrease of
H2O2 plasma membrane permeability during adaptation to H2O2 in
Saccharomyces cerevisiae. J. Biol. Chem. 279, 6501–6506.
Bronzetti, G., Della Croce, C., Galli, A., 1992. Antimutagenicity in yeast.
Mutat. Res. 267, 193–200.
Bronzetti, G., Cini, M., Andreoli, E., Caltavuturo, L., Panunzio, M.,
Della Croce, C., 2001. Protective effects of vitamins and selenium
compounds in yeast. Mutat. Res. 496, 105–115.
Brun, S., Aubry, C., Lima, O., Filmon, R., Berge `s, T., Chabasse, D.,
Bouchara, J.P., 2003. Relationships between respiration and suscep-
tibility to azole antifungals in Candida glabrata. Antimicrob. Agents
Chemother. Mar. 2003, 847–853.
Bruni, R., Medici, A., Andreotti, E., Fantin, C., Muzzoli, M., Dehesa, M.,
2003. Chemical composition and biological activities of Isphingo
essential oil, a traditional Ecuadorian spice from Ocotea quixos (Lam.)
Kosterm. (Lauraceae) flower calices. Food Chem. 85, 415–421.
Budhiraja, S.S., Cullum, M.E., Sioutis, S.S., Evangelista, L., Habanova,
S.T., 1999. Biological activity of Melaleuca alternifolia (Tea Tree) oil
component, terpinen-4-ol, in human myelocytic cell line HL-60. J.
Manipulative Physiol. Ther. 22, 447–453.
Buhagiar, J.A., Podesta, M.T., Wilson, A.P., Micallef, M.J., 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 articulata. Anticancer Res. 19, 5435–5444.
Burfield, T., Reekie, S.L., 2005. Mosquitoes, malaria and essential oils.
Inter. J. Aromather. 15, 30–41.
Burkey, J.L., Sauer, J.M., McQueen, C.A., Sipes, I.G., 2000. Cytotoxicity
and genotoxicity of methyleugenol and related congeners – a mech-
anism of activation for methyleugenol. Mutat. Res. 453, 25–33.
Burt, S., 2004. Essential oils: their antibacterial properties
potential applications in foods – a review. Int. J. Food Microbiol.
Cal, K., 2006. Skin penetration of terpenes from essential oils and topical
vehicles. Planta Med. 72, 311–316.
Candan, F., Unlu, M., Tepe, B., Daferera, D., Polissiou, M., So ¨kmen, A.,
Akpulat, H.A., 2003. Antioxidant and antimicrobial activity of the
essential oil and methanol extracts of Achillea millefolium subsp.
millefolium Afan. (Asteraceae). J. Ethnopharmacol. 87, 215–220.
Cao, G., Sofic, E., Prior, R.L., 1997. Antioxidant and prooxidant
behavior of flavonoids: structure–activity relationships. Free Radic.
Biol. Med. 22, 749–760.
Carnesecchi, S., Bras-Gonc ¸alves, R., Bradaia, A., Zeisel, M., Gosse ´, F.,
Poupon, M.F., Raul, F., 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–
Carson, C.F., Mee, B.J., Riley, T.V., 2002. Mechanism of action of
Melaleuca alternifolia (tea tree) oil on Staphylococcus aureus deter-
mined by time-kill, lysis, leakage and salt tolerance assays and electron
microscopy. Antimicrob. Agents Chemother. 46, 1914–1920.
Carson, C.F., Riley, T.V., 2003. Non-antibiotic therapies for infectious
diseases. Commun. Dis. Intell. 27, S143–S146.
Carson, C.F., Hammer, K.A., Riley, T.V., 2006. Melaleuca alternifolia
(Tea Tree) oil: a review of antimicrobial and other medicinal
properties. Clin. Microbiol. Rev. 19, 50–62.
Carvalho de Sousa, A., Sales Alviano, D., Fitzgerald Blank, A., Barreto
Alves, P., Sales Alviano, C., Rocha Gattass, C., 2004. Melissa
officinalis L. essential oil: antitumoral and antioxidant activities. J.
Pharm. Pharmacol. 56, 677–681.
Cavaleiro, C., Pinto, E., Goncalves, M.J., Salgueiro, L., 2006. Antifungal
activity of Juniperus essential oils against dermatophyte, Aspergillus
and Candida strains. J. Appl. Microbiol. 100, 1333–1338.
Chaiyasit, D., Choochote, W., Rattanachanpichai, E., Chaithong, U.,
Chaiwong, P., Jitpakdi, A., Tippawangkosol, P., Riyong, D., Pitasa-
wat, B., 2006. Essential oils as potential adulticides against two
populations of Aedes aegypti, the laboratory and natural field strains,
in Chiang Mai province, northern Thailand. Parasitol. Res. 99, 715–
Champakaew, D., Choochote, W., Pongpaibul, Y., Chaithong, U.,
Jitpakdi, A., Tuetun, B., Pitasawat, B., 2007. Larvicidal efficacy and
biological stability of a botanical natural product, zedoary oil-
impregnated sand granules, against Aedes aegypti (Diptera, Culicidae).
Parasitol. Res. 100, 729–737.
Chen, Y.C., Shen, S.C., Chow, J.M., Ko, C.H., Tseng, S.W., 2004.
Flavone inhibition of tumor growth via apoptosis in vitro and in vivo.
Int. J. Oncol. 25, 661–670.
Cheng, S.S., Chang, H.T., Wu, C.L., Chang, S.T., 2007. Anti-termitic
activities of essential oils from coniferous trees against Coptotermes
formosanus. Bioresour. Technol. 98, 456–459.
Cheung, L.M., Cheung, P.C.K., Ooi, V.E.C., 2003. Antioxidant activity
and total phenolics of edible mushroom extracts. Food Chem. 81, 249–
Choochote, W., Chaiyasit, D., Kanjanapothi, D., Rattanachanpichai, E.,
Jitpakdi, A., Tuetun, B., Pitasawat, B., 2005. Chemical composition
and anti-mosquito potential of rhizome extract and volatile oil derived
from Curcuma aromatica against Aedes aegypti (Diptera: Culicidae).
J. Vector Ecol. 30, 302–309.
Chu, Y.H., Chang, C.L., Hsu, H.F., 2000. Flavonoid content of several
vegetables and their antioxidant activity. J. Sci. Food Agri. 80, 561–
Chung, M.J., Kang, A.Y., Park, S.O., Park, K.W., Jun, H.J., Lee, S.J.,
2007. The effect of essential oils of dietary wormwood (Artemisia
princeps), with and without added vitamin E, on oxidative stress and
some genes involved in cholesterol metabolism. Food Chem. Toxicol.
Clark, S.F., 2002. The biochemistry of antioxidants revisited. Nutr. Clin.
Pract. 17, 5–17.
Cloyd, R.A., Chiasson, H., 2007. Activity of an essential oil derived from
Chenopodium ambrosioides on greenhouse insect pests. J. Econ.
Entomol. 100, 459–466.
Collins, A.R., 2005. Antioxidant intervention as a route to cancer
prevention. Eur. J. Cancer 41, 1923–1930.
Conner, D.E., Beuchat, L.R., Worthington, R.E., Hitchcock, H.L., 1984.
Effects of essential oils and oleoresins of plants on ethanol production,
respiration and sporulation of yeasts. Inter. J. Food Microbiol. 1, 63–
Cowan, M.M., 1999. Plant products as antimicrobial agents. Clin.
Microbiol. Rev., 564–582.
Cox, S.D., Mann, C.M., Markham, J.L., Bell, H.C., Gustafson, J.E.,
Warmington, J.R., Wyllie, S.G., 2000. The mode of antimicrobial
action of essential oil of Melaleuca alternifolia (tea tree oil). J. Appl.
Microbiol. 88, 170–175.
Croteau, R., Kutchan, T.M., Lewis, N.G., 2000. Natural products
(secondary metabolites). In: Buchanan, B., Gruissem, W., Jones, R.
(Eds.), Biochemistry and Molecular Biology of Plants. American
Society of Plant Physiologists.
Crowell, P.L., 1999. Prevention and therapy of cancer by dietary
monoterpenes. J. Nutr. 129, 775S–778S.
Czarnecka, A.M., Golik, P., Bartnik, E., 2006. Mitochondrial DNA
mutations in human neoplasia. J. Appl. Genet. 47, 67–78.
De Flora, S., Izzotti, A., Bennicelli, C., 1985. Mechanisms of antimuta-
genesis and genotoxicity assay of oil dispersants in bacteria (mutation,
differential lethality, SOS DNA-repair) and yeast (mitotic crossing-
over). Mutat. Res. 158, 19–30.
De Flora, S., Ramel, C., 1988. Mechanisms of inhibitors of mutagenesis
and carcinogenesis. Classification and overview. Mutat. Res. 202, 285–
De Flora, S., Camoirano, A., D’Agostini, F., Balansky, R., 1992a.
Modulation of the mutagenic response in prokaryotes. Mutat. Res.
De Flora, S., Bronzetti, G., Sobels, F.H. (Eds.), 1992b. Assessment of
antimutagenicity and anticarcinogenicity, end-points and systems.
Mutat. Res. 267, 153–298.
De Flora, S., Bagnasco, M., Vainio, H., 1999. Modulation of genotoxic
and related effects by carotenoids and vitamin A in experimental
models: mechanistic issues. Mutagenesis 14, 153–172.
Delaquis, P.J., Stanich, K., Girard, B., Mazza, G., 2002. Antimicrobial
activity of individual and mixed fractions of dill, cilantro, coriander
and eucalyptus essential oils. Int. J. Food Microbiol. 74, 101–109.
De Logu, A., Loy, G., Pellerano, M.L., Bonsignore, L., Schivo, M.L.,
2000. Inactivation of HSV-1 and HSV-2 and prevention of cell-to-cell
virus spread by Santolina insularis essential oil. Antivir. Res. 48, 177–
De-Oliveira, A.C.A.X., Ribeiro-Pinto, L.F., Paumgartten, F.J.R., 1997. In
vitro inhibition of CYP2B1 monooxygenase by b-myrcene and other
monoterpenoid compounds. Toxicol. Lett. 92, 39–46.
De-Oliveira, A.C.A.X., Fidalgo-Neto, A.A., Paumgartten, F.J.R., 1999.
In vitro inhibition of liver monooxygenases by b-ionone, 1,8-cineole,
(–)-menthol and terpineol. Toxicology 135, 33–41.
Dickancaite, E., Nemeikaite, A., Kalvelyte, A., Cenas, N., 1998. Proox-
idant character of flavonoid cytotoxicity: structure-activity relation-
ships. Biochem. Mol. Biol. Int. 45, 923–930.
Dijoux, N., Guingand, Y., Bourgeois, C., Durand, S., Fromageot, C.,
Combe, C., Ferret, P.J., 2006. Assessment of the phototoxic hazard of
some essential oils using modified 3T3 neutral red uptake assay.
Toxicol. in vitro 20, 480–489.
Di Pasqua, R., Hoskins, N., Betts, G., Mauriello, G., 2006. Changes in
membrane fatty acids composition of microbial cells induced by
addiction of thymol, carvacrol, limonene, cinnamaldehyde, and
eugenol in the growing media. J. Agric. Food Chem. 54, 2745–
Di Pasqua, R., Betts, G., Hoskins, N., Edwards, M., Ercolini, D.,
Mauriello, G., 2007. Membrane toxicity of antimicrobial compounds
from essential oils. J. Agric. Food Chem. 55, 4863–4870.
Diplock, A.T., Charleux, J.L., Crozier-Willi, G., Kok, F.J., Rice-Evans,
C., Roberfroid, M., Stahl, W., Vina-Ribes, J., 1998. Functional food
science and defence against reactive oxidative species. Br. J. Nutr. 80,
Dob, T., Dahmane, D., Benabdelkader, T., Chelghoum, C., 2006. Studies
on the essential oil composition and antimicrobial activity of Thymus
algeriensis Boiss. et Reut. Int. J. Aromather. 16, 95–100.
Dolan, M.C., Dietrich, G., Panella, N.A., Montenieri, J.A., Karchesy,
J.J., 2007. Biocidal activity of three wood essential oils against Ixodes
scapularis (Acari: Ixodidae), Xenopsylla cheopis (Siphonaptera: Pulic-
idae), and Aedes aegypti (Diptera: Culicidae). J. Econ. Entomol. 100,
Duarte, M.C., Figueira, G.M., Sartoratto, A., Rehder, V.L.G., Delarme-
lina, C., 2005. Anti-Candida activity of Brazilian medicinal plants. J.
Ethnopharmacol. 97, 305–311.
Duarte, M.C., Leme, E.E., Delarmelina, C., Soares, A.A., Figueira, G.M.,
Sartoratto, A., 2007. Activity of essential oils from Brazilian medicinal
plants on Escherichia coli. J. Ethnopharmacol. 111, 197–201.
Dudai, N., Weinstein, Y., Krup, M., Rabinski, T., Ofir, R., 2005. Citral is
a new inducer of caspase-3 in tumor cell lines. Planta Med. 71, 484–
Duschatzky, C.B., Possetto, M.L., Talarico, L.B., Garcia, C.C., Michis,
F., Almeida, N.V., De Lampasona, M.P., Schuff, C., Damonte, E.B.,
2005. Evaluation of chemical and antiviral properties of essential oils
from South American plants. Antivir. Chem. Chemother. 16, 247–
Dutta, B.K., Karmakar, S., Naglot, A., Aich, J.C., Begam, M., 2007.
Anticandidal activity of some essential oils of a megabiodiversity
hotspot in India. Mycoses 50, 121–124.
Enshaieh, S., Jooya, A., Siadat, A.H., Iraji, F., 2007. The efficacy of 5%
topical tea tree oil gel in mild to moderate acne vulgaris: a randomized,
double-blind placebo-controlled study. Indian J. Dermatol. Venereol.
Leprol. 73, 22–25.
Evandri, M.G., Battinelli, L., Daniele, C., Mastrangelo, S., Bolle, P.,
Mazzanti, G., 2005. The antimutagenic activity of Lavandula angust-
ifolia (lavender) essential oil in the bacterial reverse mutation assay.
Food Chem. Toxicol. 43, 1381–1387.
Fabian, D., Sabol, M., Domaracka, K., Bujnakova, D., 2006. Essential
oils – their antimicrobial activity against Escherichia coli and effect on
intestinal cell viability. Toxicol. In Vitro 20, 1435–1445 (Erratum in:
Toxicol. In Vitro 2007, 21, 534).
Fabio, A., Cermelli, C., Fabio, G., Nicoletti, P., Quaglio, P., 2007.
Screening of the antibacterial effects of a variety of essential oils on
microorganisms responsible for respiratory infections. Phytother. Res.
Fan, P., Lou, H., 2004. Effects of polyphenols from grape seeds on
oxidative damage to cellular DNA. Mol. Cell Biochem. 267, 67–74.
Fang, J.Y., Lee, W.R., Shen, S.C., Huang, Y.L., 2006. Effect of liposome
encapsulation of tea catechins on their accumulation in basal cell
carcinomas. J. Dermatol. Sci. 42, 101–109.
Farzaneh, M., Ahmadzadeh, M., Hadian, J., Tehrani, A.S., 2006.
Chemical composition and antifungal activity of the essential oils of
three species of Artemisia on some soil-borne phytopathogens.
Commun. Agric. Appl. Biol. Sci. 71, 1327–1333.
Ferguson, L.R., Philpott, M., Karunasinghe, N., 2004. Dietary cancer and
prevention using antimutagens. Toxicology 198, 147–159.
Fisher, K., Rowe, C., Phillips, C.A., 2007. The survival of three strains of
Arcobacter butzleri in the presence of lemon, orange and bergamot
essential oils and their components in vitro and on food. Lett. Appl.
Microbiol. 44, 495–499.
Foti, M.C., Ingold, K.U., 2003. Mechanism of inhibition of lipid
peroxidation by c-terpinene, an unusual and potentially useful
hydrocarbon antioxidant. J. Agric. Food Chem. 51, 2758–2765.
Franzios, G., Mirotsou, M., Hatziapostolou, E., Kral, J., Scouras, Z.G.,
Mavragani-Tsipidou, P., 1997. Insecticidal and genotoxic activities of
mint essential oils. J. Agric. Food Chem. 45, 2690–2694.
Fujisawa, S., Atsumi, T., Kadoma, Y., Sakagami, H., 2002. Antioxidant
and prooxidant action of eugenol-related compounds and their
cytotoxicity. Toxicology 177, 39–54.
Fukumoto, L.R., Mazza, G., 2000. Assessing antioxidant and prooxi-
dant activities of phenolic compounds. J. Agric. Food Chem. 48, 3597–
Galati, G., Sabzevari, O., Wilson, J.X., O’Brien, P.J., 2002. Prooxidant
activity and cellular effects of the phenoxyl radicals of dietary
flavonoids and other polyphenolics. Toxicology 177, 91–104.
Galati, G., O’Brien, P.J., 2004. Potential toxicity of flavonoids and other
dietary phenolics: significance for their chemopreventive and antican-
cer properties. Free Radic. Biol. Med. 37, 287–303.
Ghalfi, H., Benkerroum, N., Doguiet, D.D., Bensaid, M., Thonart, P.,
2007. Effectiveness of cell-adsorbed bacteriocin produced by Lactoba-
cillus curvatus CWBI-B28 and selected essential oils to control Listeria
monocytogenes in pork meat during cold storage. Lett. Appl.
Microbiol. 44, 268–273.
Goggelmann, W., Schimmer, O., 1983. Mutagenicity testing of beta-
asarone and commercial calamus drugs with Salmonella typhimurium.
Mutat. Res. 121, 191–194.
Gomes-Carneiro, M.R., Felzenszwalb, I., Paumgartten, F.J.R., 1998.
Mutagenicity testing of (±)-camphor, 1,8-cineole, citral, citronellal,
(?)-menthol and terpineol with the Salmonella/microsome assay.
Mutat. Res. 416, 129–136.
Gomes-Carneiro, M.R., De-Oliveira, A.C.A.X., De-Carvalho, R.R.,
Araujo, I.B., Souza, C.A., Kuriyama, S.N., Paumgartten, F.J.R.,
2003. Inhibition of cyclophosphamide-induced teratogenesis by b-
ionone. Toxicol. Lett. 138, 205–213.
Gomes-Carneiro, M.R., Dias, D.M.M., De-Oliveira, A.C.A.X., Paum-
gartten, F.J.R., 2005. Evaluation of mutagenic and antimutagenic
activities of a-bisabolol in the Salmonella/microsome assay. Mutat.
Res. 585, 105–112.
Gopanraj, G., Dan, M., Shiburaj, S., Sethuraman, M.G., George, V.,
2005. Chemical composition and antibacterial activity of the rhizome
oil of Hedychium larsenii. Acta Pharm. 55, 315–320.
Gorelick, N.J., 1995. Genotoxicity of trans-anethole in vitro. Mutat. Res.
Grassmann, J., 2005. Terpenoids as plant antioxidants. Vitam. Horm. 72,
Guba, R., 2001. Toxicity myths – essential oils and their carcinogenic
potential. Int. J. Aromather. 11, 76–83.
Gustafson, J.E., Liew, Y.C., Chew, S., Markham, J.L., Bell, H.C., Wyllie,
S.G., Warmington, J.R., 1998. Effects of tea tree oil on Escherichia coli.
Lett. Appl. Microbiol. 26, 194–198.
Hadi, S.M., Asad, S.F., Singh, S., Ahmad, A., 2000. Putative mechanism
for anticancer and apoptosis-inducing properties of plant-derived
polyphenolic compounds. IUBMB Life 50, 167–171.
Hajhashemi, V., Ghannadi, A., Sharif, B ., 2003. Anti-inflammatory and
analgesic properties of the leaf extracts and essential oil of Lavandula
angustifolia Mill. J. Ethnopharmacol. 89, 67–71.
Hammer, K.A., Carson, C.F., Riley, T.V., 2002. In vitro activity of
Melaleuca alternifolia (tea tree) oil against dermatophytes and other
filamentous fungi. J. Antimicrob. Chemother. 50, 195–199.
Hammer, K.A., Carson, C.F., Riley, T.V., 2004. Antifungal effects of
Melaleuca alternifolia (tea tree) oil and its components on Candida
albicans, Candida glabrata and Saccharomyces cerevisiae. J. Antimic-
rob. Chemother. 53, 1081–1085.
Hanbali, F.E.L., Akssira, M., Ezoubeiri, A., Gadhi, C.E.A., Mellouki, F.,
Benherraf, A., Blazquez, A.M., Boira, H., 2005. Chemical composition
and antibacterial activity of essential oil of Pulicaria odora L. J.
Ethnopharmacol. 99, 399–401.
Hansen, J.M., Go, Y.M., Jones, D.P., 2006. Nuclear and mitochondrial
compartmentation of oxidative stress and redox signaling. Annu. Rev.
Pharmacol. Toxicol. 46, 215–234.
Harris, R., 2002. Progress with superficial mycoses using essential oils. Int.
J. Aromather. 12, 83–91.
Hartman, P.E., Shankel, D.M., 1990. Antimutagens and anticarcinogens:
a survey of putative interceptor molecules. Environ. Mol. Mutagen. 15,
Hasheminejad, G., Caldwell, J., 1994. Genotoxicity of the alkenylbenz-
enes a- and b-asarone, myristicin and elimicin as determined by the
UDS assay in cultured rat hepatocytes. Food Chem. Toxicol. 32, 223–
Hata, T., Sakaguchi, I., Mori, M., Ikeda, N., Kato, Y., Minamino, M.,
Watabe, K., 2003. Induction of apoptosis by Citrus paradisi essential
oil in human leukemic (HL-60) cells. In Vivo 17, 553–559.
Hatimi, S., Boudouma, M., Bichichi, M., Chaib, N., Idrissi, N.G., 2001. In
vitro evaluation of antileishmania activity of Artemisia herba alba
Asso. Bull. Soc. Pathol. Exot. 94, 29–31.
Hayashi, K., Kamiya, M., Hayashi, T., 1995. Virucidal effects of the steam
distillate from Houttuynia cordata and its components on HSV-1,
influenza virus, and HIV. Planta Med. 61, 237–241.
Helander, I.M., Alakomi, H.L., Latva-Kala, K., Mattila-Sandholm, T.,
Pol, I., Smid, E.J., Gorris, L.G.M., Von Wright, A., 1998. Charac-
terization of the action of selected essential oil components on Gram-
negative bacteria. J. Agric. Food Chem. 46, 3590–3595.
Hernandez, T., Canales, M., Avila, J.G., Garcia, A.M., Martinez, A.,
Caballero, J., Romo de Vivar, A., Lira, R., 2005. Composition and
antibacterial activity of essential oil of Lantana achyranthifolia Desf.
(Verbenaceae). J. Ethnopharmacol. 96, 551–554.
Hernandez-Ceruelos, A., Madrigal-Bujaidar, E., de la Cruz, C., 2002.
Inhibitory effect of chamomile essential oil on the sister chromatid
exchanges induced by daunorubicin and methyl methanesulfonate in
mouse bone marrow. Toxicol. Lett. 135, 103–110.
Hierro, I., Valero, A., Pe ´rez, P., Gonzalez, P., Cabo, M.M., Montilla,
M.P., Navarro, M.C., 2004. Action of different monoterpenic com-
pounds against Anisakis simplex s.I. L3 larvae. Phytomedicine 11, 77–
Hoet, S., Ste ´vigny, C., He ´rent, M.F., Quetin-Leclercq, J., 2006. Antitry-
panosomal compounds from leaf essential oil of Strychnos spinosa.
Planta Med. 72, 480–482.
Holley, R.A., Dhaval, P., 2005. Improvement in shelf-life and safety of
perishable foods by plant essential oils and smoke antimicrobials.
Food Microbiol. 22, 273–292.
Hong, E.J., Na, K.J., Choi, I.G., Choi, K.C., Jeung, E.B., 2004.
Antibacterial and antifungal effects of essential oils from coniferous
trees. Biol. Pharm. Bull. 27, 863–866.
Horvathova, E., Sramkova, M., Labaj, J., Slamenova, D., 2006. Study of
cytotoxic, genotoxic and DNA-protective effects of selected plant
essential oils on human cells cultured in vitro. Neuroendocrinol. Lett.
Hu ¨snu ¨ Can Baser, K., Demirci, B., Iscan, G., Hashimoto, T., Demirci, F.,
Noma, Y., Asakawa, Y., 2006. The essential oil constituents and
antimicrobial activity of Anthemis aciphylla BOISS. var. discoidea
BOISS. Chem. Pharm. Bull. (Tokyo) 54, 222–225.
Idaomar, M., El Hamss, R., Bakkali, F., Mezzoug, N., Zhiri, A., Baudoux,
D., Munoz-Serrano, A., Liemans, V., Alonso-Moraga, A., 2002.
Genotoxicity and antigenotoxicity of some essential oils evaluated by
wing spot test of Drosophila melanogaster. Mutat. Res. 513, 61–68.
Inouye, S., Uchida, K., Nishiyama, Y., Hasumi, Y., Yamaguchi, H., Abe,
S., 2007. Combined effect of heat, essential oils and salt on the
fungicidal activity against Trichophyton mentagrophytes in foot bath.
Nippon Ishinkin Gakkai Zasshi. 48, 27–36.
Ioannou, E., Poiata, A., Hancianu, M., Tzakou, O., 2007. Chemical
composition and in vitro antimicrobial activity of the essential oils of
flower heads and leaves of Santolina rosmarinifolia L. from Romania.
Nat. Prod. Res. 21, 18–23.
Ipek, E., Zeytinoglu, H., Okay, S., Tuylu, B.A., Kurkcuoglu, M., Husnu
Can Baser, K., 2005. Genotoxicity and antigenotoxicity of Origanum
oil and carvacrol evaluated by Ames Salmonella/microsomal test.
Food Chem. 93, 551–556.
Jafarian, A., Ghannadi, A., Monajemi, R., Oryan, S., Haeri-Roohani, A.,
2006. Evaluation of cytotoxicity of essential oils of some Iranian Citrus
peels. In: Symposium on Perfume, Aromatic and Medicinal Plants,
from production to valorization: SIPAM 2006, 2-4 November 2006,
Jassim, S.A., Naji, M.A., 2003. A Review. Novel antiviral agents: a
medicinal plant perspective. J. Appl. Microbiol. 95, 412–427.
Jimenez Del Rio, M., Velez-Pardo, C., 2004. Transition metal-induced
apoptosis in lymphocytes via hydroxyl radical generation, mitochon-
dria dysfunction, and caspase-3 activation: an in vitro model for
neurodegeneration. Arch. Med. Res. 35, 185–193.
Juven, B.J., Kanner, J., Schved, F., Weisslowicz, H., 1994. Factors that
interact with the antibacterial action of thyme essential oil and its
active constituents. J. Appl. Bacteriol. 76, 626–631.
Kachadourian, R., Day, B.J., 2006. Flavonoid-induced glutathione-
depletion: potential implications for cancer treatment. Free Radic.
Biol. Med. 41, 65–76.
Kada, T., Shimoi, K., 1987. Desmutagens and bio-antimutagens – their
modes of action. Bioessays 7, 113–116.
Kalemba, D., Kunicka, A., 2003. Antibacterial and antifungal properties
of essential oils. Curr. Med. Chem. 10, 813–829.
Karpouhtsis, I., Pardali, E., Feggou, E., Kokkini, S., Scouras, Z.G.,
Mavragani-Tsipidou, P., 1998. Insecticidal and genotoxic activities of
oregano essential oils. J. Agric. Food Chem. 46, 1111–1115.
Kim, S.G., Liem, A., Stewart, B.C., Miller, J.A., 1999. New studies on
trans-anethole oxide and trans-asarone oxide. Carcinogenesis 20,
Kloog, Y., Cox, A.D., 2004. Prenyl-binding domains: potential targets for
Ras inhibitors and anti-cancer drugs. Semin. Cancer Biol. 14, 253–
Knio, K.M., Usta, J., Dagher, S., Zournajian, H., Kreydiyyeh, S., 2007.
Larvicidal activity of essential oils extracted from commonly used
herbs in Lebanon against the seaside mosquito Ochlerotatus caspius.
Bioresour. Technol. Mar 15 (Epub ahead of print).
Knobloch, K., Pauli, A., Iberl, B., Weigand, H., Weis, N., 1989.
Antibacterial and antifungal properties of essential oil components.
J. Essen. Oil Res. 1, 119–128.
Kordali, S., Kotan, R., Mavi, A., Cakir, A., Ala, A., Yildirim, A., 2005.
Determination of the chemical composition and antioxidant activity of
the essential oil of Artemisia dracunculus and of the antifungal and
antibacterial activities of Turkish Artemisia absinthium, A. dracunculus,
Artemisia santonicum, and Artemisia spicigera essential oils. J. Agric.
Food Chem. 53, 9452–9458.
Kosalec, I., Pepeljnjak, S., Kustrak, D., 2005. Antifungal activity of fluid
extract and essential oil from anise fruits (Pimpinella anisum L.,
Apiaceae). Acta Pharm. 55, 377–385.
Kouninki, H., Haubruge, E., Noudjou, F.E., Lognay, G., Malaisse, F.,
Ngassoum, M.B., Goudoum, A., Mapongmetsem, P.M., Ngamo, L.S.,
Hance, T., 2005. Potential use of essential oils from Cameroon applied
as fumigant or contact insecticides against Sitophilus zeamais Motsch.
(Coleoptera: Curculionidae). Commun. Agric. Appl. Biol. Sci. 70, 787–
Kubo, I., Fujita, K., Kubo, A., Nihei, K., Ogura, T., 2004. Antibacterial
activity of coriander volatile compounds against Salmonella cholerae-
suis. J. Agric. Food Chem. 52, 3329–3332.
Kulisic, T., Radoni, A., Katalinic, V., Milos, M., 2004. Use of different
methods for testing antioxidative activity of oregano essential oil.
Food Chem. 85, 633–640.
Kumar, R., Mishra, A.K., Dubey, N.K., Tripathi, Y.B., 2007. Evaluation
of Chenopodium ambrosioides oil as a potential source of antifungal,
antiaflatoxigenic and antioxidant activity. Int. J. Food Microbiol. 115,
Kuo, M.L., Lee, K.C., Lin, J.K., 1992. Genotoxicities of nitropyrenes and
their modulation by apigenin, tannic acid, ellagic acid and indole-3-
carbinol in the Salmonella and CHO systems. Mutat. Res. 270, 87–
Kuroda, Y., Inoue, T., 1988. Antimutagenesis by factors affecting DNA
repair in bacteria. Mutat. Res. 202, 387–391.
Lahlou, M., Berrada, R., 2001. Potential of essential oils in schistosomi-
asis control in Morocco. Int. J. Aromather. 11, 87–96.
Lai, F., Wissing, S.A., Muller, R.H., Fadda, A.M., 2006. Artemisia
arborescens L essential oil-loaded solid lipid nanoparticles for potential
agricultural application: preparation and characterization. AAPS
Pharm. Sci. Tech. 7, E2.
Lambert, R.J.W., Skandamis, P.N., Coote, P., Nychas, G.J.E., 2001. A
study of the minimum inhibitory concentration and mode of action of
oregano essential oil, thymol and carvacrol. J. Appl. Microbiol. 91,
Lamiri, A., Lhaloui, S., Benjilali, B., Berrada, M., 2001. Insecticidal effects
of essential oils against Hessian fly, Mayetiola destructor (Say). Field
Crops Res. 71, 9–15.
Lazutka, J.R., Mierauskien, J., Slap, G., Dedonyt, V., 2001. Genotoxicity
of dill (Anethum graveolens L.), peppermint (Mentha piperita L.) and
pine (Pinus sylvestris L.) essential oils in human lymphocytes and
Drosophila melanogaster. Food Chem. Toxicol. 39, 485–492.
Lee, S.B., Cha, K.H., Kim, S.N., Altantsetseg, S., Shatar, S., Sarangerel,
O., Nho, C.W., 2007a. The antimicrobial activity of essential oil from
Dracocephalum foetidum against pathogenic microorganisms. J. Micro-
biol. 45, 53–57.
Lee, S.J., Han, J.I., Lee, G.S., Park, M.J., Choi, I.G., Na, K.J., Jeung,
E.B., 2007b. Antifungal effect of eugenol and nerolidol against
Microsporum gypseum in a guinea pig model. Biol. Pharm. Bull. 30,
Legault, J., Dahl, W., Debiton, E., Pichette, A., Madelmont, J.C., 2003.
Antitumor activity of balsam fir oil: production of reactive oxygen
species induced by alpha-humulene as possible mechanism of action.
Planta Med. 69, 402–407.
Lin, Y.T., Kwon, Y.I., Labbe, R.G., Shetty, K., 2005. Inhibition of
Helicobacter pylori and associated urease by Oregano and Cranberry
phytochemical synergies. Appl. Environm. Microbiol. 71, 8558–8564.
Liu, C.J., Chen, C.L., Chang, K.W., Chu, C.H., Liu, T.Y., 2000. Safrole in
betel quid may be a risk factor for hepatocellular carcinoma: case
report. Can. Med. Ass. J. 162, 359–360.
Liu, J., Shen, H.M., Ong, C.M., 2001. Role of intracellular thiol depletion,
mitochondrial dysfunction and reactive oxygen species in Salvia
miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells. Life
Sci. 69, 1833–1850.
Liu, C.H., Mishra, A.K., Tan, R.X., Tang, C., Yang, H., Shen, Y.F.,
2006. Repellent and insecticidal activities of essential oils from
Artemisia princeps and Cinnamomum camphora and their effect on
seed germination of wheat and broad bean. Bioresour. Technol. 97,
Lo Cantore, P., Iacobellis, N.S., De Marco, A., Capasso, F., Senatore, F.,
2004. Antibacterial activity of Coriandrum sativum L. and Foeniculum
vulgare Miller Var. vulgare (Miller) essential oils. J. Agric. Food Chem.
Longbottom, C.J., Carson, C.F., Hammer, K.A., Mee, B.J., Riley, T.V.,
2004. Tolerance of Pseudomonas aeruginosa to Melaleuca alternifolia
(tea tree) oil is associated with the outer membrane and energy-
dependent cellular processes. J. Antimicrob. Chemother. 54, 386–392.
Lopez, P., Sanchez, C., Batlle, R., Nerin, C., 2007. Vapor-phase activities
of Cinnamon, Thyme, and Oregano essential oils and key constituents
against foodborne microorganisms. J. Agric. Food Chem. 55, 4348–
Lowe, G.M., Vlismas, K., Young, A.J., 2003. Carotenoids as prooxidants?
Mol. Aspects Med. 24, 363–369.
Lu, Y., Zhao, Y.P ., Wang, Z.C., Chen, S.Y., Fu, C.X., 2007.
Composition and antimicrobial activity of the essential oil of Actinidia
macrosperma from China. Nat. Prod. Res. 21, 227–233.
Luximon-Ramma, A., Bahorun, T., Soobrattee, M.A., Aruoma, O.I.,
2002. Antioxidant activities of phenolic, proanthocyanidin, and
flavonoid components in extracts of Cassia fistula. J. Agric. Food
Chem. 50, 5042–5047.
Manohar, V., Ingram, C., Gray, J., Talpur, N.A., Echard, B.W., Bagchi,
D., Preuss, H.G., 2001. Antifungal activities of origanum oil against
Candida albicans. Mol. Cell. Biochem. 228, 111–117.
Manosroi, J., Dhumtanom, P., Manosroi, A., 2006. Anti-proliferative
activity of essential oil extracted from Thai medicinal plants on KB
and P388 cell lines. Cancer Lett. 235, 114–120.
Maralhas, A., Monteiro, A., Martins, C., Kranendonk, M., Laires, A.,
Rueff, J., Rodrigues, A.S., 2006. Genotoxicity and endoreduplication
inducing activity of the food flavouring eugenol. Mutagenesis 21, 199–
Martin, K.R., 2006. Targeting apoptosis with dietary bioactive agents.
Exp. Biol. Med. 231, 117–129.
Masotti, V., Juteau, F., Bessie `re, J.M., Viano, J., 2003. Seasonal and
phenological variations of the essential oil from the narrow endemic
species Artemisia molinieri and its biological activities. J. Agric. Food
Chem. 51, 7115–7121.
Mazie `res, J., Pradines, A., Favre, G., 2003. Les inhibiteurs de farne ´syl
transfe ´rase: une cible peut en cacher une autre. Me ´decine/Sciences 19,
Mazie `res, J., Pradines, A., Favre, G., 2004. Perspectives on farnesyl
transferase inhibitors in cancer therapy. Cancer Lett. 206, 159–167.
McMahon, M.A., Blair, I.S., Moore, J.E., McDowell, D.A., 2007.
Habituation to sub-lethal concentrations of tee tree oil (Melaleuca
alternifolia) is associated with reduced susceptibility to antibiotics in
human pathogens. J. Antimicrob. Chemother. 59, 125–127.
Mehta, R., Templeton, D.M., O’Brien, P.J., 2006. Mitochondrial
involvement in genetically determined transition metal toxicity II.
Copper toxicity. Chem. Biol. Interact. 163, 77–85.
Metodiewa, D., Jaiswal, A.K., Cenas, N., Dickancaite, E., Segura-
Aguilar, J., 1999. Quercetin may act as a cytotoxic prooxidant after its
metabolic activation to semiquinone and quinoidal product. Free
Radic. Biol. Med. 26, 107–116.
Mezzoug, N., Elhadri, A., Dallouh, A., Amkiss, S., Skali, N.S., Abrini, J.,
Zhiri, A., Baudoux, D., Diallo, B., El Jaziri, M., Idaomar, M., 2007.
Investigation of the mutagenic and antimutagenic effects of Origanum
compactum essential oil and some of its constituents. Mutat. Res. 629,
Miller, E.C., Swanson, A.B., Phillips, D.H., Fletcher, T.L., Liem, A.,
Miller, J.A., 1983. Structure–activity studies of the carcinogenicities in
the mouse and rat of some naturally occurring and synthetic
alkenylbenzene derivatives related to safrole and estragole. Cancer
Res. 43, 1124–1134.
Mimica-Dukic, N., Kujundzic, S., Sokovic, M., Couladis, M., 2003.
Essential oil composition and antifungal activity of Foeniculum vulgare
Mill. obtained by different distillation conditions. Phytother. Res. 17,
Mimica-Dukic, N., Bozin, B., Sokovic, M., Simin, N., 2004. Antimicrobial
and antioxidant activities of Melissa officinalis L. (Lamiaceae) essential
oil. J. Agric. Food Chem. 52, 2485–2489.
Monzote, L., Montalvo, A.M., Almanonni, S., Scull, R., Miranda, M.,
Abreu, J., 2006. Activity of the essential oil from Chenopodium
ambrosioides grown in Cuba against Leishmania amazonensis. Chemo-
therapy 52, 130–136.
Moon, T., Wilkinson, J.M., Cavanagh, H.M., 2006. Antiparasitic activity
of two Lavandula essential oils against Giardia duodenalis, Tricho-
monas vaginalis and Hexamita inflata. Parasitol. Res. 99, 722–
Morais, S.M., Cavalcanti, E.S., Bertini, L.M., Oliveira, C.L., Rodrigues,
J.R., Cardoso, J.H., 2006. Larvicidal activity of essential oils from
Brazilian Croton species against Aedes aegypti L. J. Am. Mosq.
Control Assoc. 22, 161–164.
Morales-Ramirez, P., Madrigal-Bujaidar, E., Mercader-Martinez, J.,
Cassini, M., Gonzalez, G., Chamorro-Cevallos, G., Salazar-Jacobo,
M., 1992. Sister chromatid exchange induction produced by in vivo and
in vitro exposure to a-asarone. Mutat. Res. 279, 269–273.
Morin, D., Barthelemy, S., Zini, R., Labidalle, S., Tillement, J.P., 2001.
Curcumin induces the mitochondrial permeability transition pore
mediated by membrane protein thiol oxidation. FEBS Lett. 495, 131–
Muller, L., Kasper, P., Muller-Tegethoff, K., Petr, T., 1994. The genotoxic
potential in vitro and in vivo of the allyl benzene etheric oils estragole,
basil oil and trans-anethole. Mutat. Res. 325, 129–136.
Nemeikaite-Ceniene, A., Imbrasaite, A., Sergediene, E., Cenas, N., 2005.
Quantitative structure–activity relationships in prooxidant cytotoxicity
of polyphenols: role of potential of phenoxyl radical/phenol redox
couple. Arch. Biochem. Biophys. 441, 182–190.
Nestman, E.R., Lee, E.G.H., 1983. Mutagenicity of constituents of pulp
and paper mill effluent in growing cells of Saccharomyces cerevisiae.
Mutat. Res. 119, 273–280.
NTP (National Toxicology Program) (1990) Toxicology and carcinogen-
esis studies of d-Limonene (CAS N? 5989-27-5) in F344/N rats and
B6C3F1 mice (gavage studies). Natl. Toxicol. Program Tech. Rep. Ser.
347, pp. 1–165.
Novgorodov, S.A., Gudz, T.I., 1996. Permeability transition pore of the
inner mitochondrial membrane can operate in two open states with
different selectivities. J. Bioenerg. Biomembr. 28, 139–146.
O’Brien, J., Wilson, I., Orton, T., Pognan, F., 2000. Investigation of the
Alamar Blue (resazurin) fluorescent dye for the assessment of
mammalian cell cytotoxicity. Eur. J. Biochem. 267, 5421–5426.
Odin, A.P., 1997. Vitamins as antimutagens: advantages and some
possible mechanisms of antimutagenic action. Mutat. Res. 386, 39–
Ohizumi, H., Masuda, Y., Yoda, M., Hashimoto, S., Aiuchi, T., Nakajo,
S., Sakai, I., Ohsawa, S., Nakaya, K., 1997. Induction of apoptosis in
various tumor cell lines by geranylgeraniol. Anticancer Res. 17, 1051–
Oliveira, N.G., Rodrigues, A.S., Chaveca, T., Rueff, J., 1997. Induction of
an adaptive response to quercetin, mitomycin C and hydrogen
peroxide by low doses of quercetin in V79 Chinese hamster cells.
Mutagenesis 12, 457–462.
Oussalah, M., Caillet, S., Lacroix, M., 2006. Mechanism of action of
Spanish oregano, Chinese cinnamon, and savory essential oils against
cell membranes and walls of Escherichia coli O157:H7 and Listeria
monocytogenes. J. Food Prot. 69, 1046–1055.
Oussalah, M., Caillet, S., Salmieri, S., Saucier, L., Lacroix, M., 2007.
Antimicrobial effects of alginate-based films containing essential oils
on Listeria monocytogenes and Salmonella typhimurium present in
bologna and ham. J. Food Prot. 70, 901–908.
Ozer, H., Sokmen, M., Gulluce, M., Adiguzel, A., Sahin, F., Sokmen, A.,
Kilic, H., Baris, O., 2007. Chemical composition and antimicrobial
and antioxidant activities of the essential oil and methanol extract of
Hippomarathrum microcarpum (Bieb.) from Turkey. J. Agric. Food
Chem. 55, 937–942.
Paik, S.Y., Koh, K.H., Beak, S.M., Paek, S.H., Kim, J.A., 2005. The
essential oils from Zanthoxylum schinifolium pericarp induce apoptosis
of HepG2 human hepatoma cells through increased production of
reactive oxygen species. Biol. Pharm. Bull. 28, 802–807.
Palozza, P., Serini, S., Di Nicuolo, F., Calviello, G., 2004. Modulation of
apoptotic signalling by carotenoids in cancer cells. Arch. Biochem.
Biophys. 430, 104–109.
Park, I.K., Choi, K.S., Kim, D.H., Choi, I.H., Kim, L.S., Bak, W.C.,
Choi, J.W., Shin, S.C., 2006a. Fumigant activity of plant essential oils
and components from horseradish (Armoracia rusticana), anise
(Pimpinella anisum) and garlic (Allium sativum) oils against Lycoriella
ingenua (Diptera: Sciaridae). Pest. Manage. Sci. 62, 723–728.
Park, I.K., Kim, L.S., Choi, I.H., Lee, Y.S., Shin, S.C., 2006b. Fumigant
activity of plant essential oils and components from Schizonepeta
tenuifolia against Lycoriella ingenua (Diptera: Sciaridae). J. Econ.
Entomol. 99, 1717–1721.
Parveen, M., Hasan, M.K., Takahashi, J., Murata, Y., Kitagawa, E.,
Kodama, O., Iwahashi, H., 2004. Response of Saccharomyces cerevi-
siae to a monoterpene: evaluation of antifungal potential by DNA
microarray analysis. J. Antimicrob. Chemother. 54, 46–55.
Pauli, A., 2006. Anticandidal low molecular compounds from higher
plants with special reference to compounds from essential oils. Med.
Res. Rev. 26, 223–268.
Pavela, R., 2005. Insecticidal activity of some essential oils against larvae
of Spodoptera littoralis. Fitoterapia 76, 691–696.
Pawar, V.C., Thaker, V.S., 2006. In vitro efficacy of 75 essential oils
against Aspergillus niger. Mycoses 49, 316–323.
Peana, A.T., Moretti, M.D.L., Juliano, C., 1999. Chemical composition
and antimicrobial action of the essential oils of Salvia desoleana and
Salvia sclarea. Planta Med. 65, 752–754.
Pepeljnjak, S., Kosalec, I., Kalodera, Z., Blazevic, N., 2005. Antimicrobial
activity of juniper berry essential oil (Juniperus communis L.,
Cupressaceae). Acta Pharm. 55, 417–422.
Perry, N.S., Bollen, C., Perry, E.K., Ballard, C., 2003. Salvia for dementia
therapy: review of pharmacological activity and pilot tolerability
clinical trial. Pharmacol. Biochem. Behav. 75, 651–659.
Pichersky, E., Noel, J.P., Dudareva, N., 2006. Biosynthesis of plant
volatiles: nature’s diversity and ingenuity. Science 311, 808–811.
Pitarokili, D., Couladis, M., Petsikos-Panayotarou, N., Tzakou, O., 2002.
Composition and antifungal activity on soil-borne pathogens of the
essential oil of Salvia sclarea from Greece. J. Agric. Food Chem. 50,
Pitarokili, D., Tzakou, O., Loukis, A., Harvala, C., 2003. Volatile
metabolites from Salvia fruticosa as antifungal agents in soilborne
pathogens. J. Agric. Food Chem. 51, 3294–3301.
Pitasawat, B., Champakaew, D., Choochote, W., Jitpakdi, A., Chaithong,
U., Kanjanapothi, D., Rattanachanpichai, E., Tippawangkosol, P.,
Riyong, D., Tuetun, B., Chaiyasit, D., 2007. Aromatic plant-derived
essential oil: An alternative larvicide for mosquito control. Fitoterapia
Pithayanukul, P., Tubprasert, J., Wuthi-Udomlert, M., 2007. In vitro
antimicrobial activity of Zingiber cassumunar (Plai) oil and a 5% Plai
oil gel. Phytother. Res. 21, 164–169.
Pizzale, L., Bortolomeazzi, R., Vichi, S., U¨beregger, E., Conte, L.S., 2002.
Antioxidant activity of sage (Salvia officinalis and S. fruticosa) and
oregano (Origanum onites and O. indercedens) extracts related to their
phenolic compound content. J. Sci. Food Agr. 82, 1645–1651.
Prabuseenivasan, S., Jayakumar, M., Ignacimuthu, S., 2006. In vitro
antibacterial activity of some plant essential oils. BMC Compl. Altern.
Med. 6, 39.
Priestley, C.M., Burgess, I.F., Williamson, F.M., 2006. Lethality of
essential oil constituents towards the human louse, Pediculus humanus,
and its eggs. Fitoterapia 77, 303–309.
Pyun, M.S., Shin, S., 2006. Antifungal effects of the volatile oils from
Allium plants against Trichophyton species and synergism of the oils
with ketoconazole. Phytomedicine 13, 394–400.
Rafii, F., Shahverdi, A.R., 2007. Comparison of essential oils from three
plants for enhancement of antimicrobial activity of nitrofurantoin
against enterobacteria. Chemotherapy 53, 21–25.
Ramassamy, C., 2006. Emerging role of polyphenolic compounds in the
treatment of neurodegenerative diseases: a review of their intracellular
targets. Eur. J. Pharmacol. 545, 51–64.
Ramel, C., Alekperov, U.K., Ames, B.N., Kada, T., Wattenberg, L.W.,
1986. International Commission for Protection against environmental
mutagens and carcinogens. ICPEMC Publication N? 12. Inhibitors of
mutagenesis and their relevance to carcinogenesis. Report by ICPEMC
expert group on antimutagens and desmutagens. Mutat. Res. 168, 47–
Ravi Kiran, S., Bhavani, K., Sita Devi, P., Rajeswara Rao, B.R.,
Janardhan Reddy, K., 2006. Composition and larvicidal activity of
leaves and stem essential oils of Chloroxylon swietenia DC against
Aedes aegypti and Anopheles stephensi. Bioresour. Technol. 97, 2481–
Reichling, J., Koch, C., Stahl-Biskup, E., Sojka, C., Schnitzler, P., 2005.
Virucidal activity of a beta-triketone-rich essential oil of Leptosper-
mum scoparium (manuka oil) against HSV-1 and HSV-2 in cell culture.
Planta Med. 71, 1123–1127.
Richter, C., Schlegel, J., 1993. Mitochondrial calcium release induced by
prooxidants. Toxicol. Lett. 67, 119–127.
Rim, I.S., Jee, C.H., 2006. Acaricidal effects of herb essential oils against
Dermatophagoides farinae and D. pteronyssinus (Acari: Pyroglyphidae)
and qualitative analysis of a herb Mentha pulegium (pennyroyal).
Korean J. Parasitol. 44, 133–138.
Romero-Jimenez, M., Campos-Sanchez, J., Analla, M., Munoz-Serrano,
A., Alonso-Moraga, A., 2005. Genotoxicity and anti-genotoxicity of
some traditional medicinal herbs. Mutat. Res. 585, 147–155.
Rosato, A., Vitali, C., De Laurentis, N., Armenise, D., Antonietta
Milillo, M., 2007. Antibacterial effect of some essential oils adminis-
tered alone or in combination with Norfloxacin. Phytomedicine 14,
Rota, C., Carraminana, J.J., Burillo, J., Herrera, A., 2004. In vitro
antimicrobial activity of essential oils from aromatic plants against
selected foodborne pathogens. J. Food Prot. 67, 1252–1256.
Ruberto, G., Baratta, M.T., 2000. Antioxidant activity of selected
essential oil components in two lipid model systems. Food Chem. 69,
Sacchetti, G., Maietti, S., Muzzoli, M., Scaglianti, M., Manfredini, S.,
Radice, M., Bruni, R., 2005. Comparative evaluation of 11 essential
oils of different origin as functional antioxidants, antiradicals and
antimicrobials in food. Food Chem. 91, 621–632.
Saı ¨dana, D., Mahjoub, M.A., Boussaada, O., Chriaa, J., Che ´raif, I.,
Daami, M., Mighri, Z., Helal, A.N., 2007. Chemical composition and
antimicrobial activity of volatile compounds of Tamarix boveana
(Tamaricaceae). Microbiol. Res. Jan 12 (Epub ahead of print).
Sakagami, H., Satoh, K., 1997. Prooxidant action of two antioxidants:
ascorbic acid and gallic acid. Anticancer Res. 17, 221–224.
Sakagami, H., Oi, T., Satoh, K., 1999. Prevention of oral diseases by
polyphenols (Review). In vivo 13, 155–172.
Sakihama, Y., Cohen, M.F., Grace, S.C., Yamasaki, H., 2002. Plant
phenolic antioxidant and prooxidant activities: phenolics-induced
oxidative damage mediated by metals in plants. Toxicology 177, 67–
Saleh, M.A., Belal, M.H., el-Baroty, G., 2006. Fungicidal activity of
Artemisia herba alba Asso (Asteraceae). J. Environ. Sci. Health B. 41,
Salim, E.I., Fukushima, S., 2003. Chemopreventive potential of volatile oil
from black cumin (Nigella sativa L.) seeds against rat colon carcino-
genesis. Nutr. Cancer. 45, 195–202.
Santana-Rios, G., Orner, G.A., Amantana, A., Provost, C ., Wu, S.Y.,
Dashwood, R.H., 2001. Potent antimutagenic activity of white tea in
comparison with green tea in the Salmonella assay. Mutat. Res. 495,
Santoro, G.F., Cardoso, M.G., Guimaraes, L.G., Mendonca, L.Z.,
Soares, M.J., 2007a. Trypanosoma cruzi: Activity of essential oils
from Achillea millefolium L., Syzygium aromaticum L. and Ocimum
basilicum L. on epimastigotes and trypomastigotes. Exp. Parasitol.
Santoro, G.F., das Gracas Cardoso, M., Guimaraes, L.G., Salgado, A.P.,
Menna-Barreto, R.F., Soares, M.J., 2007b. Effect of Oregano (Orig-
anum vulgare L.) and Thyme (Thymus vulgaris L.) essential oils on
Trypanosoma cruzi (Protozoa: Kinetoplastida) growth and ultrastruc-
ture. Parasitol. Res. 100, 783–790.
Sartorelli, P., Marquioreto, A.D., Amaral-Baroli, A., Lima, M.E.,
Moreno, P.R., 2007. Chemical composition and antimicrobial activity
of the essential oils from two species of Eucalyptus. Phytother. Res. 21,
Saura-Calixto, F., Goni, I., 2006. Antioxidant capacity of the Spanish
Mediterranean diet. Food Chem. 94, 442–447.
Schelz, Z., Molnar, J., Hohmann, J., 2006. Antimicrobial and antiplasmid
activities of essential oils. Fitoterapia 77, 279–285.
Schmolz, E., Doebner, R., Auste, R., Daum, R., Welge, G., Lamprecht, I.,
1999. Bioenergetic investigations on tea-tree and related essential oils.
Thermochim. Acta 337, 71–81.
Schnitzler, P., Koch, C., Reichling, J., 2007. Susceptibility of drug-
resistant clinical HSV-1 strains to essential oils of Ginger, Thyme,
Hyssop and Sandalwood. Antimicrob. Agents Chemother. 51, 1859–
Schwartz, J., Shklar, G., Trickler, D., 1993. Vitamin C enhances the
development of carcinomas in the hamster buccal pouch experimental
model. Oral Surg. Oral Med. Oral Pathol. 76, 718–722.
Schwartz, J.L., 1996. The dual roles of nutrients as antioxidants and
prooxidants: their effects on tumor cell growth. J. Nutr. 126, 1221S–
Segvic-Klaric, M., Kosalec, I., Mastelic, J., Pieckova, E., Pepeljnak, S.,
2007. Antifungal activity of thyme (Thymus vulgaris L.) essential oil
and thymol against moulds from damp dwellings. Lett. Appl.
Microbiol. 44, 36–42.
Sekizawa, J., Shibamoto, T., 1982. Genotoxicity of safrole related
chemicals in microbial test systems. Mutat. Res. 101, 127–140.
Serrano, M., Martinez-Romero, D., Castillo, S., Guille ´n, F., Valero, D.,
2005. The use of natural antifungal compounds improves the beneficial
effect of MAP in sweet cherry storage. Innov. Food Sci. Emerg. Tech.
Shankel, D.M., Kuo, S., Haines, C., Mitscher, L.A., 1993. Extracellular
interception of mutagens. Basic Life Sci. 61, 65–74.
Sharma, N., Trikha, P., Athar, M., Raisuddin, S., 2001. Inhibition of
benzo(a)pyrene- and cyclophosphamide-induced mutagenicity by Cin-
namomum cassia. Mutat. Res., 179–188.
Shen, S.C., Ko, C.H., Tseng, S.W., Tsai, S.H., Chen, Y.C., 2004.
Structurally related antitumor effects of flavonones in vitro and in vivo:
involvement of caspase 3 activation, p21 gene expression, and reactive
oxygen species production. Toxicol. Appl. Pharmacol. 197, 84–95.
Shyamala, B.N., Gupta, S., Lakshmi, A.J., Prakash, J., 2005. Leafy
vegetable extracts, antioxidant activity and effect on storage stability of
heated oils. Innov. Food Sci. Emerg. Tech. 6, 239–245.
Si, W., Gong, J., Tsao, R., Zhou, T., Yu, H., Poppe, C., Johnson, R., Du,
Z., 2006. Antimicrobial activity of essential oils and structurally related
synthetic food additives towards selected pathogenic and beneficial gut
bacteria. J. Appl. Microbiol. 100, 296–305.
Sies, H., Cadenas, E., 1985. Oxidative stress :damage to intact cells
and organs. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 311, 617–
Sikkema, J., De Bont, J.A .M., Poolman, B., 1994. Interactions of cyclic
hydrocarbons with biological membranes. J. Biol. Chem. 269, 8022–
Silva, J., Abebe, W., Sousa, S.M., Duarte, V.G., Machado, M.I.L., Matos,
F.J.A., 2003. Analgesic and anti-inflammatory effects of essential oils
of Eucalyptus. J. Ethnopharmacol. 89, 277–283.
Sim, M.J., Choi, D.R., Ahn, Y.J., 2006. Vapor phase toxicity of plant
essential oils to Cadra cautella (Lepidoptera: Pyralidae). J. Econ.
Entomol. 99, 593–598.
Singh, G., Kapoor, I.P., Pandey, S.K., Singh, U.K., Singh, R.K., 2002.
Studies on essential oils: part 10; antibacterial activity of volatile oils of
some spices. Phytother. Res. 16, 680–682.
Singh, G., Marimuthu, P., de Heluani, C.S., Catalan, C.A., 2006.
Antioxidant and biocidal activities of Carum nigrum (seed) essential
oil, oleoresin, and their selected components. J. Agric. Food Chem. 54,
Sinico, C., De Logu, A., Lai, F., Valenti, D., Manconi, M., Loy, G.,
Bonsignore, L., Fadda, A.M., 2005. Liposomal incorporation of
Artemisia arborescens L. essential oil and in vitro antiviral activity.
Eur. J. Pham. Biopharm. 59, 161–168.
Skerget, M., Kotnik, P., Hadolin, M., Hras, A.R., Simonie, M., Knez, Z.,
2005. Phenols, proanthocyanidins, flavones and flavonols in some
plant materials and their antioxidant activities. Food Chem. 89, 191–
Slamenova, D., Horvathova, E., Sramkova, M., Marsalkova, L., 2007.
DNA-protective effects of two components of essential plant oils
carvacrol and thymol on mammalian cells cultured in vitro. Neopl-
asma 54, 108–112.
Smith, R.L., Cohen, S.M., Doull, J., Feron, V.J., Goodman, J.I., Marnett,
L.J., Portoghese, P.S., Waddell, W.J., Wagner, B.M., Hall, R.L.,
Higley, N.A., Lucas-Gavin, C., Adams, T.B., 2005. A procedure for
the safety evaluation of natural flavor complexes used as ingredients in
food: essential oils. Food Chem. Toxicol. 43, 345–363.
So ¨derberg, T.A., Johansson, A., Gref, R., 1996. Toxic effects of some
conifer resin acids and tea tree oil on human epithelial and fibroblast
cells. Toxicology 107, 99–109.
Sonboli, A., Eftekhar, F., Yousefzadi, M., Kanani, M.R., 2005. Antibac-
terial activity and chemical composition of the essential oil of
Grammosciadium platycarpum Boiss. from Iran. Z. Naturforsch. 60c,
Sonboli, A., Mirjalili, M.H., Hadian, J., Ebrahimi, S.N., Yousefzadi, M.,
2006a. Antibacterial activity and composition of the essential oil of
Ziziphora clinopodioides subsp. bungeana (Juz.) Rech. f. from Iran. Z.
Naturforsch. 61c, 677–680.
Sonboli, A., Babakhani, B., Mehrabian, A.R., 2006b. Antimicrobial
activity of six constituents of essential oil from Salvia. Z. Naturforsch.
Song, L., Ding, J.Y., Tang, C., Yin, C.H., 2007. Compositions and
biological activities of essential oils of Kadsura longepedunculata and
Schisandra sphenanthera. Am. J. Chin. Med. 35, 353–364.
Soobrattee, M.A., Neergheen, V.S., Luximon-Ramma, A., Aruoma, O.I.,
Bahorun, T., 2005. Phenolics as potential antioxidant therapeutic
agents: mechanism and actions. Mutat. Res. 579, 200–213.
Soylu, E.M., Soylu, S., Kurt, S., 2006. Antimicrobial activity of the
essential oils of various plants against tomato late blight disease agent
Phytophthora infestans. Mycopathologia 161, 119–128.
Stadler, R.H., Markovic, J., Turesky, R.J., 1995. In vitro anti- and pro-
oxidative effects of natural polyphenols. Biol. Trace Elem. Res. 47,
Stammati, A., Bonsi, P., Zucco, F., Moezelaar, R., Alakomi, H.L., von
Wright, A., 1999. Toxicity of selected plant volatiles in microbial and
mammalian short-term assays. Food Chem. Toxicol. 37, 813–823.
Sun, A., Chia, J.S., Chiang, C.P., Hsuen, S.P., Du, J.L., Wu, C.W., Wang,
W.B., 2005a. The chinese herbal medicine Tien-Hsien liquid inhibits
cell growth and induces apoptosis in a wide variety of human cancer
cells. J. Altern. Complement Med. 11, 245–256.
Sun, H., Sun, C., Pan, Y., 2005b. Cytotoxic activity and constituents of
the volatile oil from the roots of Patrinia scabra Bunge. Chem.
Biodivers. 2, 1351–1357.
Surh, Y.J., 2002. Anti-tumor promoting potential of selected spice
ingredients with antioxidative and anti-inflammatory activities: a short
review. Food Chem. Toxicol. 40, 1091–1097.
Sylvestre, M., Legault, J., Dufour, D., Pichette, A., 2005. Chemical
composition and anticancer activity of leaf essential oil of Myrica gale
L. Phytomedicine 12, 299–304.
Sylvestre, M., Pichette, A., Longtin, A., Nagau, F., Legault, J., 2006.
Essential oil analysis and anticancer activity of leaf essential oil of
Croton flavens L. from Guadeloupe. J. Ethnopharmacol. 103, 99–102.
Tabanca, N., Demirci, B., Baser, K.H.C., Aytac, Z., Ekici, M., Khan, S.I.,
Jacob, M.R., Wedge, D.E., 2006. Chemical composition and anti-
fungal activity of Salvia macrochlamys and Salvia recognita essential
oils. J. Agric. Food Chem. 54, 6593–6597.
Tabanca, N., Demirci, B., Husnu Can Baser, K., Mincsovics, E., Khan,
S.I., Jacob, M.R., Wedge, D.E., 2007. Characterization of volatile
constituents of Scaligeria tripartita and studies on the antifungal
activity against phytopathogenic fungi. J. Chromatogr. B Analyt.
Technol. Biomed. Life Sci. 850, 221–229.
Tawatsin, A., Asavadachanukorn, P., Thavara, U., Wongsinkongman, P.,
Bansidhi, J., Boonruad, T., Chavalittumrong, P., Soonthornchareon-
non, N., Komalamisra, N., Mulla, M.S., 2006. Repellency of essential
oils extracted from plants in Thailand against four mosquito vectors
(Diptera: Culicidae) and oviposition deterrent effects against Aedes
aegypti (Diptera: Culicidae). Southeast Asian J. Trop. Med. Public
Health 37, 915–931.
Tepe, B., Daferera, D., So ¨kmen, M., Polissiou, M., So ¨kmen, A., 2004a.
The in vitro antioxidant and antimicrobial activities of the essential oil
and various extracts of Origanum syriacum L. var. bevanii. J. Sci. Food
Agric. 84, 1389–1396.
Tepe, B., Daferera, D., So ¨kmen, M., Polissiou, M., So ¨kmen, A., 2004b. In
vitro antimicrobial and antioxidant activities of the essential oils and
various extracts of Thymus eigii M Zohary et P.H. Davis. J. Agric.
Food Chem. 52, 1132–1137.
Trevisan, M.T., Vasconcelos Silva, M.G., Pfundstein, B., Spiegelhalder,
B., Owen, R.W., 2006. Characterization of the volatil pattern and
antioxidant capacity of essential oils from different species of the genus
Ocimum. J. Agric. Food Chem. 54, 4378–4382.
Tsuneki, H., Ma, E.L., Kobayashi, S., Sekizaki, N., Maekawa, K.,
Sasaoka, T., Wang, M.W., Kimura, I., 2005. Antiangiogenic activity of
beta-eudesmol in vitro and in vivo. Eur. J. Pharmacol. 512, 105–115.
Tuberoso, C.I., Kowalczyk, A., Coroneo, V., Russo, M.T., Dessi, S.,
Cabras, P., 2005. Chemical composition and antioxidant, antimicro-
bial, and antifungal activities of the essential oil of Achillea ligustica
all. J. Agric. Food Chem. 53, 10148–10153.
Turina, A.V., Nolan, M.V., Zygadlo, J.A., Perillo, M.A., 2006. Natural
terpenes: self-assembly and membrane partitioning. Biophys. Chem.
Ultee, A., Kets, E.P., Alberda, M., Hoekstra, F.A., Smid, E.J., 2000.
Adaptation of the food-borne pathogen Bacillus cereus to carvacrol.
Arch. Microbiol. 174, 233–238.
Ultee, A., Bennik, M.H., 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.
Van de Sande, W.W.J., Fahal, A.H., Riley, T.V., Verbrugh, H., Van
Belkum, A., 2007. In vitro susceptibility of Madurella mycetomatis,
prime agent of Madura foot, to tea tree oil and artemisinin. J.
Antimicrob. Chemother. 59, 553–555.
Van Houten, B., Woshner, V., Santos, J.H., 2006. Role of mitochondrial
DNA in toxic responses to oxidative stress. DNA Repair 5, 145–
Van Tol, R.W., Swarts, H.J., Van der Linden, A., Visser, J.H., 2007.
Repellence of the red bud borer Resseliella oculiperda from grafted
apple trees by impregnation of rubber budding strips with essential
oils. Pest Manage. Sci. 63, 483–490.
Velluti, A., Sanchis, V., Ramos, A.J., Egido, J., Marin, S., 2003.
Inhibitory effect of cinnamon, clove, lemongrass, oregano and palma-
rose essential oils on growth and fumonisin B1production by Fusarium
proliferatum in maize grain. Int. J. Food Microbiol. 89, 145–154.
Velluti, A., Sanchis, V., Ramos, A.J., Turon, C., Marin, S., 2004. Impact
of essential oils on growth rate, zearalenone and deoxynivalenol
production by Fusarium graminearum under different temperature and
water activity conditions in maize grain. J. Appl. Microbiol. 96, 716–
Vercesi, A.E., Kowaltowski, A.J., Grijalba, M.T., Meinicke, A.R.,
Castilho, R.F., 1997. The role of reactive oxygen species in mitochon-
drial permeability transition. Biosci. Rep. 17, 43–52.
Vinson, J.A., Su, X., Zubik, L., Bose, P., 2001. Phenol antioxidant
quantity and quality in foods: fruits. J. Agric. Food Chem. 49, 5315–
Vukovic-Gacic, B., Nikcevic, S., Beric-Bjedov, T., Knezevic-Vukcevic, J.,
Simic, D., 2006. Antimutagenic effect of essential oil of sage (Salvia
officinalis L.) and its monoterpenes against UV-induced mutations in
Escherichia coli and Saccharomyces cerevisiae. Food Chem. Toxicol.
Wang, S.Y., Chen, P.F., Chang, S.T., 2005. Antifungal activities of
essential oils and their constituents from indigenous cinnamon
(Cinnamomum osmophloeum) leaves against wood decay fungi. Biores.
Technol. 96, 813–818.
Waters, M.D., Stack, H.F., Jackson, M.A., Brockman, H.E., De Flora, S.,
1996. Activity profiles of antimutagens: in vitro and in vivo data.
Mutat. Res. 350, 109–129.
Weisburger, J.H., 1999. Antimutagens, anticarcinogens, and effective
worldwide cancer prevention. J. Environ. Pathol. Toxicol. Oncol. 18,
Williams, L.R., Stockley, J.K., Yan, W., Home, V.N., 1998. Essential oils
with high antimicrobial activity for therapeutic use. Int. J. Aromather.
Wu, X., Beecher, G.R., Holden, J.M., Haytowitz, D.B., Gebhardt, S.E.,
Prior, R.L., 2004. Lipophilic and hydrophilic antioxidant capacities of
common foods in the United States. J. Agric. Food Chem. 52, 4026–
Wu, X.J., Stahl, T., Hu, Y., Kassie, F., Mersch-Sundermann, V., 2006.
The production of reactive oxygen species and the mitochondrial
membrane potential are modulated during onion oil-induced cell cycle
arrest and apoptosis in A549 cells. J. Nutr. 136, 608–613.
Yang, L., McRae, R., Henary, M.M., Patel, R., Lai, B., Vogt, S., Fahrni,
C.J., 2005. Imaging of the intracellular topography of copper with a
fluorescent sensor and by synchrotron X-ray fluorescence microscopy.
Proc. Natl. Acad. Sci. USA 102, 11179–11184.
Yang, P., Ma, Y., 2005. Repellent effect of plant essential oils against
Aedes albopictus. J. Vector. Ecol. 30, 231–234.
Yang, Y.C., Lee, E.H., Lee, H.S., Lee, D.K., Ahn, Y.J., 2004a. Repellency
of aromatic medicinal plant extracts and a steam distillate to Aedes
aegypti. J. Am. Mosq. Control Assoc. 20, 146–149.
Yang, Y.C., Lee, H.S., Clark, J.M., Ahn, Y.J., 2004b. Insecticidal activity
of plant essential oils against Pediculus humanus capitis (Anoplura:
Pediculidae). J. Med. Entomol. 41, 699–704.
Yoo, C.B., Han, K.T., Cho, K.S., Ha, J., Park, H.J., Nam, J.H., Kil,
U.H., Lee, K.T., 2005. Eugenol isolated from the essential oil of
Eugenia caryophyllata induces a reactive oxygen species-mediated
apoptosis in HL-60 human promyelocytic leukemia cells. Cancer Lett.
Yoon, H.S., Moon, S.C., Kim, N.D., Park, B.S., Jeong, M.H., Yoo, Y.H.,
2000. Genistein induces apoptosis of RPE-J cells by opening mito-
chondrial PTP. Biochem. Biophys. Res. Commun. 276, 151–156.
Young, A.J., Lowe, G.M., 2001. Antioxidant and prooxidant properties of
carotenoids. Arch. Biochem. Biophys. 385, 20–27.
Zani, F., Massino, G., Benvenuti, S., Bianchi, A., Albasini, A., Melegari,
M., Vampa, G., Bellotti, A., Mazza, P., 1991. Studies on the genotoxic
properties of essential oils with Bacillus subtilis rec-assay and
Salmonella/microsome reversion assay. Planta Med. 57, 237–241.
Zheng, S., Yang, H., Zhang, S., Wang, X., Yu, L., Lu, J., Li, J., 1997.
Initial study on naturally occurring products from traditional Chinese
herbs and vegetables for chemoprevention. J. Cell. Biochem. Suppl. 27,
Zhou, S., Koh, H.L., Gao, Y., Gong, Z.Y., Lee, E.J., 2004. Herbal
bioactivation: the good, the bad and the ugly. Life Sci. 74, 935–968.