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Exploring the anticancer properties of essential oils from family Lamiaceae

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Lamiaceae is among the largest families of flowering plants with about 250 genera and over 7,000 species distributed around the world. It is considered as the important source of essential oils, for example, menthol, geraniol, eucalyptol, camphor and thymol. Therefore, it is imperative to study these economically important compounds under in vitro conditions for their sustainable and enhanced production. In addition to proven biological activities, essential oils from this family have recently been evaluated for anticancer activities and considered as a source of anticancer drugs. Mechanisms involved in the essential oils-mediated antiproliferative activity include cell cycle arrest, apoptosis and DNA repair mechanisms. Essential oils also act in the reduction of tumors, inhibiting metastasis and as anti-multidrug resistance molecules. The aim of this review is to assess the anticancer properties of essential oils obtained from different members of family Lamiaceae. The available reports on active components of essential oils and their effect on cancer type and cell line have been discussed. Biotechnological studies to improve the production of essential oils have also been highlighted. Various methods have been adopted to obtain essential oils under in vitro conditions from different plant species of family Lamiaceae, and their production is affected by culture conditions, cultivation mode, utilization of nutrient media and plant growth regulators. The literature survey suggests that essential oils obtained from family Lamiaceae have perspective for the development of new alternatives for disease treatment and prevention.
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Exploring the anticancer properties of essential
oils from family Lamiaceae
Ludmilla Santos Silva de Mesquita, Tássio Rômulo Silva Araújo Luz, José
Wilson Carvalho de Mesquita, Denise Fernandes Coutinho, Flavia Maria
Mendonça do Amaral, Maria Nilce de Sousa Ribeiro & Sonia Malik
To cite this article: Ludmilla Santos Silva de Mesquita, Tássio Rômulo Silva Araújo Luz, José
Wilson Carvalho de Mesquita, Denise Fernandes Coutinho, Flavia Maria Mendonça do Amaral,
Maria Nilce de Sousa Ribeiro & Sonia Malik (2018): Exploring the anticancer properties of essential
oils from family Lamiaceae, Food Reviews International
To link to this article: https://doi.org/10.1080/87559129.2018.1467443
Published online: 09 May 2018.
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Exploring the anticancer properties of essential oils from
family Lamiaceae
Ludmilla Santos Silva de Mesquita
a
, Tássio Rômulo Silva Araújo Luz
a
,
José Wilson Carvalho de Mesquita
a
, Denise Fernandes Coutinho
a
,
Flavia Maria Mendonça do Amaral
a
, Maria Nilce de Sousa Ribeiro
a
, and Sonia Malik
b
a
Department of Pharmacy, Biological and Health Sciences Center, Federal University of Maranhão, São Luís,
Brazil;
b
Graduate Program in Health Sciences, Biological and Health Sciences Center, Federal University of
Maranhão, São Luís, Brazil
ABSTRACT
Lamiaceae is among the largest families of owering plants with
about 250 genera and over 7,000 species distributed around the
world. It is considered as the important source of essential oils, for
example, menthol, geraniol, eucalyptol, camphor and thymol.
Therefore, it is imperative to study these economically important
compounds under in vitro conditions for their sustainable and
enhanced production. In addition to proven biological activities,
essential oils from this family have recently been evaluated for antic-
ancer activities and considered as a source of anticancer drugs.
Mechanisms involved in the essential oils-mediated antiproliferative
activity include cell cycle arrest, apoptosis and DNA repair mechan-
isms. Essential oils also act in the reduction of tumors, inhibiting
metastasis and as anti-multidrug resistance molecules. The aim of
this review is to assess the anticancer properties of essential oils
obtained from dierent members of family Lamiaceae. The available
reports on active components of essential oils and their eect on
cancer type and cell line have been discussed. Biotechnological
studies to improve the production of essential oils have also been
highlighted. Various methods have been adopted to obtain essential
oils under in vitro conditions from dierent plant species of family
Lamiaceae, and their production is aected by culture conditions,
cultivation mode, utilization of nutrient media and plant growth
regulators. The literature survey suggests that essential oils obtained
from family Lamiaceae have perspective for the development of new
alternatives for disease treatment and prevention.
KEYWORDS
Bioactive compounds;
cancer; geraniol; menthol;
pharmacology; plant cell
culture; volatile compounds
Introduction
Cancer is a worldwide public health problem, which involves uncontrolled growth of cells.
The cells lose their interaction with each other, invade neighboring tissues and nally
spread to distant tissues of the body. It is one of the leading causes of death in both
developed and developing countries.
[1,2]
According to data collected by International
Agency for Research in Cancer, there were about 14.1 million new cancer cases and 8.2
million deaths attributed to cancer in 2012.
[3]
Among all types of cancers, lung, breast,
CONTACT Sonia Malik 777soniamalik@gmail.com Graduate Program in Health Sciences, Biological and Health
Sciences Center, Federal University of Maranhão, 65085-580 São Luís, MA, Brazil.
Color versions of one or more of the gures in the article can be found online at www.tandfonline.com/lfri.
FOOD REVIEWS INTERNATIONAL
https://doi.org/10.1080/87559129.2018.1467443
© 2018 Taylor & Francis
colorectum, prostate, stomach, and liver are the most prevalent in both sexes, which
accounts for 55% incidence globally in 2012.
[2]
Most cancer cases (4.1 million) and deaths
(2.75 million) were recorded in Eastern Asia with large population.
[4]
About 70% new
cases of cancer are expected over the next two decades. This is largely due to the extension
of life expectancy and age of population. In addition, people are increasingly exposed to
carcinogenic risk factors, such as tobacco use, overweight/obesity, and others changes in
behavior and lifestyles.
[1,2]
The drastic epidemiological prole of cancer around all over the world requires
priorities in the allocation of resources to modify this scenario. It can be achieved with
planning and eective actions, an integrated and active system of disease surveillance,
development of research for prevention and control of the disease as well as its risk
factors.
[5]
Although considerable progress has been made in recent years in anticancer
therapy (chemotherapy, radiotherapy, surgery, and/or bone marrow transplantation),
advances in research for nding more eective and secure drugs are required.
[58]
Natural resources, especially of plant origin, represent important source of drugs in
the process of discovery and development of new pharmacologically active
compounds.
[912]
The various ecosystems of planet possess rich, diverse, and scienti-
cally unknown ora. The advances in analytical techniques and biological sciences
have enabled the studies to evaluate the therapeutic potential of various plant species,
especially those of traditional popular use. These can eectively contribute to the
production of new bioactive products, semi-synthetic medicines or as prototype for
the synthesis of more active and/or selective molecules.
[13,14]
Ethnobotanical and ethnopharmacological studies have eectively contributed to the
research and development of essential drugs in the current therapeutic arsenal for
various types of cancer.
[15,16]
Taxol and camptothecin, two famous eective anticancer
agents, were discovered and developed by US National Cancer Institute during a drug
screening of thousand plants.
[17]
Thereafter, many other plant-derived compounds with
anticancer potential were discovered. During the past decade, essential oils (EOs) have
been studied for their potential to treat cancer diseases.
[18,19]
Variousmechanismsare
involved in the EOs-mediated antiproliferative activity, which include cell cycle arrest,
apoptosis, DNA repair. EOs also act in the reduction of tumors, by inhibiting metastasis
and as anti-multidrug resistance molecules.
[20]
Essential oils
EOs are a complex mixture of volatile, liquid, odorous, and avor substances synthesized
by plants. These are also known as volatile or ethereal oil due to their vaporous feature.
Plant species producing EOs are classied as aromatic and normally can be identied by
their distinctive and characteristic aroma and odor.
[21]
There are approximately 3,000 EOs
identied from dierent plants species, especially from Angiospermic families such as
Lamiaceae, Rutaceae, Verbenaceae, Asteraceae, Myrtaceae, and Zingiberaceae.
[22,23]
The components of EOs are derived mainly from the secondary metabolites of plants with
low molecular weight and lipophilic properties like terpenes, and phenylpropanoids. The
terpenes found in EOs are particularity mono- and sesquiterpenes that have two or three
isoprene hydrocarbon chains, respectively, and may show oxygenated groups such as acid,
alcohol, aldehyde, ketone, ester, phenol, or lactone.
[18,2027]
The volatile phenylpropanoids
2L. S. S. D. MESQUITA ET AL.
may occur in EOs and are considered aromatic compounds derived from shikimate pathway.
There are other classes of substances in EOs like diterpenes, sulfur compounds, coumarins,
fatty acids, phthalides, and short-chain hydrocarbons not derived from isoprene units, with or
without oxygen groups.
[2731]
The chemical composition of EOs varies depending on several genetic and environmental
factors. The plant species/variety,
[32]
plant part,
[31]
growing place,
[33]
phenological or devel-
opmental stage,
[34]
extraction procedures,
[35]
environmental and living conditions
[36]
can
extensively aect the composition of EOs. In addition, the existence of chemotypes within
the same species shows intraspecic chemical variations in EOs.
[37,38]
The volatile components of EOs are synthesized in secretory structures located in
dierent parts of the aromatic plants: leaves, owers, fruits, seeds, stems, barks, or roots.
The secretory structures or glands may be present in the surface of plants or within the
plant tissues and are considered as an important characteristic with taxonomic value that
may dierentiate families, genera, or even species. The glandular trichomes are found on
the surface of epidermis, and internal glands can be secretory cells, cavities, or ducts. In
some special cases, the EOs are not stored in special secretory structures and secreted by
regular parenchyma or epidermal cells.
[3942]
Because of lipophilic nature and volatile
properties, the components of EOs are able to cross the cell membranes, walls, and cuticles
and released into the atmosphere.
[43]
The conventional techniques to extract EOs from plant species include both steam and
hydrodistillation using Clevenger apparatus. Besides distillation, EOs can also be obtained
by expression, and EOs of most citrus fruits are generally extracted using expression
methods.
[44]
The traditional method of eneurage, originated in the Grasse region of
France, is another method to extract EOs. This process uses fats to absorb the oil of
fresh owers.
[45]
Several novel techniques have been developed, for example, headspace
solid phase microextraction (HS-SPME),
[46]
supercritical uid extraction (SFE),
[47]
micro-
wave assisted extraction apparatus (MAE),
[48]
and solvent-free microwave extraction
(SFME).
[49]
The choice of extraction technique depends on extraction time, cost, e-
ciency, environmental impact, and the purpose of usage of EOs.
[44]
EOsplayimportantecologicalrolesinplantslike defense by repelling herbivorous animals,
healing the plants wounds, and protection against microbial growth. On the other hand, EOs
released from owers attract pollinators and volatile compounds, while expelling from fruits
(after ripening) helps to attract animals seed dispersers like birds to ensure the reproduction and
perpetuation of plant species.
[43]
In addition to the physiological functions, EOs are commer-
cially important for perfume, cosmetics, sanitary products, food, and pharmaceutical industries.
Since ancient times, aromatic plants have been used in the elds of folk medicine, cosmetics, and
culinary.
[50]
Several scientic studies have proved that EOs possess important biological activ-
ities like anti-inamatory,
[51,52]
anti-nociceptive,
[53,54]
larvicidal,
[55,56]
anti-leishmania,
[57,58]
antioxidant,
[59,60]
antimicrobial,
[61,62]
molluscicidal,
[63,64]
antiviral,
[65,66]
insect repellent,
[23]
and many others.
Because of their wide range of biological activities, EOs from aromatic and medic-
inal plants have been employed for various applications in food industries. They have
been regarded as a safe alternative as compared to synthetic food additives. In addi-
tion, they improve the quality of food without leaving residues in the product or the
environment.
[67]
During the recent years, EOs and their components are also being
employed in food industries for developing lms to be used in packaging systems.
FOOD REVIEWS INTERNATIONAL 3
Because of their antimicrobial and antioxidant properties, lms with EOs may improve
the shelf life of perishable food products.
[68]
In addition to proven biological activities of EOs, these aromatic compounds have been
studied in recent years for evaluating their anticancer activities.
[69]
A search in PubMed
and Science Direct databases using the uniterms essential oiland anticancershowed
1,397 and 2,626 papers, respectively, published during the last 10 years. A review by
Alonso Castro et al.
[70]
has reported 300 plant species used in folk medicine in Mexico to
treat cancer. Out of these, many plant species belong to family Asteraceae, Lamiaceae,
Lauraceae, Myrtaceae, and Verbenaceae. In a total of 181 plant species analyzed, only 88
showed cytotoxic eects against at least one cancer cell line.
Based on chemical structures, the components of EOs are divided into ve classes, viz.,
I oxygenated monoterpenes (menthol (1), menthona (2), carvone, (3), piperitenone (4),
pulegone (5), terpinen-4-ol (6), α-thujone (7), 1,8-cineole (8), β-citronellal (9), geraniol
(10), linalool (11), camphor (12) and borneol (13)), II bicyclic monoterpene hydrocarbons
(α-pinene (14) and β-pinene (15)), III oxygenated sesquiterpenes, ((E,E)-farnesol,(16),
caryophyllene oxide (18), spathulenol (20) and γ-eudesmol (22)), IV hydrocarbons ses-
quiterpene (germacrene D (17), humulene (19), δ-cadinene (21)) and V aromatic com-
pounds (thymol (23), carvacrol (24), and methyl cinnamate (25)), as shown in Figure 1.
Considering the economical importance and rich content of EOs possessed by many
species of family Lamiaceae, the present paper is aimed to review the anticancer activities
of EOs from dierent plant species of this family.
Family Lamiaceae
Lamiaceae Martinov (1820) is the sixth largest family of owering plants in the world with
about 250 genera and over 7,000 species.
[71]
The species of this family has a cosmopolitan
distribution but mainly grows in America and Mediterranean regions.
[72]
In America,
there are around 65 genera of this family, of which 48 are natives and 17 are cultivated.
They are generally found in Andean, Amazonian and eastern South America and tempe-
rate South and Central America.
[73]
The family Lamiaceae is commonly known as mint
family, but in Asian countries it is also named as chun xing ke, irumba-hare, irumbahe, or
lumbase nilcols.
[74]
The members of Lamiaceae are mainly herbs, some shurbs, few trees, and rarely climbers.
Their stems are often quadrangular and erect to prostate. Leaves are opposite, often decussate.
The inorescence is normally bracteates, and the owers have two-lipped corolla.
[73,75]
Because of this ower feature, Lamiaceae was formerly called Labiatae Jussieu (1789). The
name of this family has been changed to standardize the ending of the families with aceae.
According to International Code of Nomenclature for algae, fungi, and plants (Melbourne
Code), Labiatea is considered as a valid or alternative name because of its wide range of
uses.
[76]
The Tropicos database cites both Labiatae and Lamiaceae as conserved names
[74]
;
however, the Plant List database does not consider the name Labiatae.
[71]
Salvia L. is the largest genera of family Lamiaceae with 960 species
[77]
followed by
Hyptis Jacquin (400),
[78]
Scutellaria L. (360),
[79]
Stachys L. (300),
[80]
Plectranthus LHéritier
(300),
[81]
Teucrium L. (250-340),
[82,83]
Vitex L. (250)
[84]
and Thymus L. (220).
[85]
Other
economically important genera include Mentha L., Lavandula L., Ocimum L., and
Melissa L.
4L. S. S. D. MESQUITA ET AL.
Plant species of Lamiaceae are cultivated for ornamental purposes because of their beautiful
owers. For instance, Nepeta L. (catmint), Salvia L. (sage), Phlomis L. (yellow-owered sage),
and Ajuga L. (bugle) are used as decorative purposes.
[86]
Also possess a diversied content of
secondary metabolites, including phenolic compounds, as avonoids or benzoic acids and
terpenoids such as mono, sesqui, di, and triterpenoids as well as steroids.
[8791]
These
secondary metabolites are responsible for dierent biological activities, including antibacter-
ial, antifungal,
[92]
antioxidant,
[93,94]
anti-inammatory,
[95]
antiviral
[96]
, and others.
Oxygenated monoterpenes
12 3
9
Bicyclic hydrocarbons monoterpenes Hydrocarbons sesquiterpenes
Oxygenated sesquiterpenes
22
Aromatic compounds
45678
10 11 12
14 15 17 19 21
16 18 20
23 24 25
Figure 1. Main anticancer chemical substances found in essential oils of species of the family
Lamiaceae.
FOOD REVIEWS INTERNATIONAL 5
Pharmacological studies have shown that the EOs in plant species of family Lamiaceae
have anticancer or antimitogenic/antiproliferative activities.
[97]
The family is mainly
known because of the aromatic properties of majority of its plant species. The EOs
produced by its various members have large culinary usage as avoring and in cosmetic,
perfume, and pharmaceutical industries as fragrances or active agents with pharmacolo-
gical activities.
[89,98]
Among Angiosperms, family Lamiaceae is considered as the most
important source of EOs with economical interest.
[72]
EOs derived from Lamiaceae have diverse composition, including mainly mono- and
sesquiterpenes as well as phenylpropanoids. Other components like fatty acid and diter-
penes have also been reported.
[98101]
Numerous studies have been performed with EO
from Lamiaceae, showing repellent,
[102,103]
larvicidal,
[104,105]
antimicrobial,
[106]
antioxidant,
[107,108]
and anticancer activities.
[109]
Mentha L. is one of the most important genus of family Lamiaceae and comprises
about 19 species and 13 natural hybrids. These are commonly known as mint, and some
of the important species are M.xpiperita L., M. spicata L., M. pulegium L., and M.
crispa L. They are fast growing plants and have been used since ancient times as
avoring agent in food and as medicinal and cosmetic purpose mainly because of
their aromatic properties. The EOs of Mentha show a variety of yield and composition
due to dierent factors related to ecotype, environment conditions as well as others
factors such as time of collection and extraction method.
[110,111]
Menthol, carvone,
pulgenone, geraniol, menthone, and α-pinene are the major components of EOs from
these plant species,
[112]
which have been reported to possess several biological activities
such as antibacterial,
[113]
antifungal,
[114]
antioxidant,
[115]
anticancer,
[116]
insecticidal, and
larvicidal.
[117,118]
Moreover, menthol, the most important monoterpene isolated from oil
of pipermint (M.xpiperita), has application in food and cosmetic industries.
[119]
Lavandula species are largely used for decorative purpose because of their purple-colored
beautiful owers. However, the main use of this plant species is found in perfume and
medicine industries. Lavandula angustifolia Mill. (formally called as Lavandula ocinalis
Chaix),
[74]
commonly known as lavendule, is the most important species from this genus. It
has been used in folk medicine as antidepressive, digestive, antiatulent, antiemetic, sedative,
diuretic, anticonvulsivant, and antimicrobial agent.
[120]
The literature studies have shown
dierent biological activities of EOs obtained from leaves and owers of this plant species,
such as antibacterial,
[121]
antischistosomal,
[122]
anti-inammatory, analgesic,
[123]
antioxidant,
and sedative.
[124]
This EO normally has monoterpenes as major components, such as
borneol and eucalyptol (1,8-cineole) in leaves
[122]
and linalool and linalyl acetate in
owers.
[125]
Among the members of Lamiaceae, the genus Thymus stands out for having many
species either natives or cultivated for their economic importance to several industries.
This genus comprises around 250 species, and all are aromatic. Many of them are
interesting for use in culinary or as ornamental and medicinal purposes.
[126]
Their EOs
possess the aromatic monoterpenes, thymol, carvacrol and p-cymene as major compo-
nents, although others non-aromatic monterpene can be found in these oils like linalool
and geraniol.
[127,128]
T. vulgaris L. (thyme) is considered one of the most important species
of this genus, and its EOs have showed several properties like antifungal, antibacterial,
[85]
antioxidant,
[129]
anti-inammatory,
[130]
and anticancer.
[18]
6L. S. S. D. MESQUITA ET AL.
Another important member of Lamiaceae is Salvia L., one of the largest genus of this
family and commonly named as sage. Salvia species are mainly used as ornamental plants
and also in culinary, cosmetic, and pharmaceutical industries. The major components
reported in EOs of Salvia are camphor, α-thujone, β-thujone, linalool, and caryophyllene.
These EOs has been demonstrated several pharmacological activities.
[131,132]
S. ocinalis
L. is one the most important species from this genus, which have been used worldwide as
food condiment, tea beverage and to treat several diseases in folk medicine. The EOs from
its leaves have mono- (1,8-cineole, α-thujone, β-thujone, camphor) and sesquiterpenes
(β-caryophyllene, α-humulene) as main components and show a wide range of biological
activities, including anticancer eect.
[133,134]
EOs in Lamiaceae plants are produced and stored in glandular trichomes, which is a
reliable character with taxonomic value for this family. The glandular trichomes in this
family show high variation in morphology, for example, peltate and capitate types.
Generally, peltate have one basal cell, one shalk cell, and four to eight secretory cells in
the head of trichome, while capitate have one basal cell, one to several shalk cells, and one
to two disc-shape secretory cells also in the top.
[135,136]
In some species, variations can be
described as digitiform and conoidal glandular trichomes.
[137]
Lamiaceae also has in the
indumentum of its aerial parts non-glandular trichomes that provide features to distin-
guish several genera.
[138]
Figure 2 depicts some glandular trichomes from dierent plant
species of Lamiaceae collected at São Luís, state of Maranhão, northeast of Brazil.
Pharmacology
The relevance of Lamiaceae species due to abundance of EOs and their popular use in
treatment of cancer has stimulated studies to prove its pharmacological potential. Table 1
shows the plant species, parts used for extracting EOs, major constituents, type of cancer,
and cell line studied. In vitro studies have carried out mainly in genera Salvia, Ocimum,
Satureja, Teucrium, and Mentha. The plant species used to obtain EOs have mostly
procured from India, Iran, Lebanon, Brazil, and Greece (countries showing abundance
of plant species from family Lamiaceae).
[72]
In most of the plant species studied, EOs were
found to be rich in mono- and sesquiterpenes, particularly in camphor (from Ocimum and
Salvia), thymol (from Monarda, Ocimum, Origanum, Satureja and Thymus), carvacrol
(from Ocimum, Origanum, Satureja, Teucrium, and Thymus), caryophyllene oxide (from
Cantinoa, Salvia, and Teucrium), linalool (Hyssopus, Lavandula, Ocimum, and Origanum)
and 1,8-cineole (from Rosmarinus and Salvia).
Melanoma is one of the most studied cancers type, which can be justied by its high
incidence in both sexes and dierent age groups in several regions of the world.
[5]
Malignant melanoma of skin accounted for about 232,000 new cases in 2012.
[4]
It is the
most rapidly increasing cancer in fair-skinned populations.
[139]
This cancer is aggressive,
often treatment-refractory, and presents high possibility of metastasis. It is possible to
perform an eective treatment when melanoma is detected at an early stage but treatment
becomes very dicult at later stages as it quickly metastasizes. Therefore, there is a need
for continuous search for new anticancer agents that are eective and non-toxic to normal
cells. Natural products, especially plant-derived EOs and their components, have been
evaluated for the treatment of cancer.
[20,140,141]
EOs perform anti-proliferative action on
FOOD REVIEWS INTERNATIONAL 7
Figure 2. Glandular trichomes of leaves from Lamiaceae species. A-E Plectranthus barbatus Andrews. F-
GPlectranthus amboinucus (Lour.) Spreng. I-J Ocimum basilicum L. K-L Ocimum gratissimum L. M-O
Plectranthus neochilus Schltr. P-S Mentha sp. A-B Peltate trichomes. C-J, L-O and S Capitate trichomes. K
and P-R Digiform trichomes. Scale bars: 50 µm.
8L. S. S. D. MESQUITA ET AL.
Table 1. Essential oils with anticancer activity from family Lamiaceae.
Plant Species Plant part
Major
constituents Cancer type (Cell Line Used) Reference
Agastache rugosa O.
Kuntze
Flowers Estragole Lung (A549), hepatocellular (Hep3B), gastric
(KATO 111) and breast (MCF7)
[184]
Anisomeles indica Kuntze Leaves Farnesyl
acetone
Hepatocellular (HepG2), leukemia (K562) and
lung (A549)
[185]
Cantinoa stricta (Benth.)
Harley & J.F.B. Pastore
Flowers Caryophyllene
oxide and cis-
pinane
Glioma (U251), melanoma (UACC-62), breast
(MCF-7), lung (NC), prostate (PC-3) and leukemia
(K562)
[186]
Leaves Caryophyllene
oxide and cis-
pinane
Glioma (U251), melanoma (UACC-62), breast
(MCF-7), lung (NC), prostate (PC-3) and
leukemia (K562)
Hyssopus ocinalis
subsp. aristatus
Aerial parts Linalool Melanoma (A375), breast (MDA-MB 231) and
colon (HCT116)
[163]
Lavandula angustifolia
Mill.
Commercial
source
Linalool and
linalyl acetate
Prostate (PC-3 and DU145) [164]
Leaves Linalool Cervical (Hela) and lung (A549) [148]
Lavandula stoechas L. Commercial
source
Not reported Lung (A549), prostate (PC-3) and breast (MCF-7) [187]
Lavandula stoechas ssp.
stoechas
Leaves Pulegone Colon (COL-2) and prostate (LNCaP) [188]
Lycopus lucidus var.
hirtus Regel
Aerial parts α-Humulene Hepatocellular (Bel-7402 and HepG2), breast
(MDA-MB-435S and ZR-7530), cervical (HeLa)
and renal (ACHN)
[62]
Marrubium vulgare L. Aerial parts γ-Eudesmol Cervical (HeLa) [189]
Melissa ocinalis L. Leaves Geranial Lung (A549), breast (MCF-7), colon (Caco-2),
leukemia (HL-60 and K562) and mouse
melanoma (B16F10)
[190]
Mentha aquatica L. Aerial parts Not reported Cervix (HeLa) and laryngeal (Hep2) [191]
Mentha arvensis L. Leaves Menthol Breast (MCF-7) and prostate (LNCaP) [161]
Mentha crispa L. Aerial parts Not reported Cervix (HeLa) and laryngeal (Hep2) [192]
Mentha longifolia (L.)
Huds
Aerial parts Not reported Cervix (HeLa) and laryngeal (Hep2) [192]
Leaves Piperitenone
oxide
Breast (MCF-7) and prostate (LNCaP) [158]
Mentha piperita L. Aerial parts Not reported Cervix (HeLa) and laryngeal (Hep2) [191]
Leaves Menthol Cervical (HeLa) and lung (A549) [148]
Menthone Breast (MCF-7) and prostate (LNCaP) [158]
Mentha pulegium L. Aerial parts Not reported Ovarian (SK-OV-3), cervix (HeLa) and lung (A549) [192]
Not reported Cervix (HeLa) and laryngeal (Hep2) [191]
Leaves Pulegone Cervical (HeLa) and lung (A549) [148]
Mentha spicata L. Aerial parts Not reported Cervix (HeLa) and laryngeal (Hep2) [191]
Commercial
source
Not reported Prostate (PC-3) [187]
Leaves Not reported Mouth epidermal (KB) and murine leukemia
(P388)
[157]
Carvone Breast (MCF-7) and prostate (LNCaP) [158]
Monarda citriodora Cerv.
ex Lag.
Leaves Thymol Prostate (PC-3), breast (MDA-MB-231 and MCF-7),
lung (A549) and leukemia (HL-60)
[159]
Nepeta sintenisii Bornm Aerial parts 4aα,7α,7aβ-
Nepetalactone
Ovarian (A2780), cervical (HeLa), colon (LS180)
and breast (MCF-7)
[161]
Nepeta ucranica L. Aerial parts Germacrene D Ovarian (A2780) and breast (MCF-7) [165]
Ocimum americanum L. Leaves Not reported Mouth epidermal (KB) and murine leukemia
(P388)
[157]
Ocimum basilicum L. Leaves Linalool Ascites carcinoma (Ehrlich) [142]
Methyl
cinnamate and
linalool
Cervical (HeLa) and laryngeal epithelial (HEp-2) [143]
Whole plant α-Terpineol Prostate (LNCaP and PC-3) and glioblastoma (SF-
767 and SF-763)
[144]
Ocimum canum Sims Leaves Camphor Breast (MCF-7) [193]
(Continued)
FOOD REVIEWS INTERNATIONAL 9
Table 1. (Continued).
Plant Species Plant part
Major
constituents Cancer type (Cell Line Used) Reference
Ocimum
kilimandscharicum
Gürke
Leaves Camphor Glioma (U251), melanoma (UACC-62), breast
(MCF-7), ovarian expressing phenotype multiple
drug resistance (NCI-ADR/RES), renal (7860),
lung (NCI-H460), prostate (PC-3), ovarian (OVCAR-
03), leukemia (K562) and colon (HT29)
[194]
Ocimum sanctum L. Leaves Not reported Mouth epidermal carcinoma (KB) and murine
leukemia (P388)
[157]
Ocimum viride Willd. Whole plant Thymol Colon (COLO 205) [8]
Origanum dictamnus L. Aerial parts Carvacrol Cervical (HeLa) and laryngeal (Hep-2) [195]
Origanum majorana L. Aerial parts Terpinen-4-ol
and thymol
Breast (MCF-7) and prostate (LNCaP) [196]
Terpinen-4-ol Laryngeal (Hep-2) and colon (HT29) [197]
Origanum onites L. Whole plant Linalool and
carvacrol
Hepatocellular (HepG2) [25]
Pistacia palaestina Boiss. Flowers β-Pinene Melanoma (C32) and adenocarcinoma (ACHN) [150]
Rosmarinus ocinalis L. Leaves 1,8-Cineole Ovarian (SK-OV-3 and HO-8910) and
hepatocellular (Bel-7402)
[147]
Hepatocellular (HepG2) [146]
Breast (MCF-7) and prostate (LNCaP) [145]
Lung (A549) [198]
Salvia aurea L. Aerial parts Caryophyllene
oxide
Melanoma (M14, A2058 and A375) [141]
Salvia bracteata Banks &
Sol.
Aerial parts Caryophyllene
oxide
Melanoma (M14) [152]
Salvia judaica Boiss. Aerial parts Caryophyllene
oxide
Melanoma (M14, A2058 and A375) [141]
Salvia lavandulifolia Vahl Aerial parts Camphor Leukemia (HL-60 and K562), breast (MCF-7) and
ovarian (A2780)
[149]
Leaves Camphor Cervical (HeLa) and lung (A549) [148]
Salvia ocinalis L. Aerial parts α-Thujone, β-
thujone and
1,8-cineole
Leukemia (HL-60 and K562), breast (MCF-7) and
ovarian (A2780)
[149]
α-Thujone,
camphor,
borneol,
sclareol
Melanoma (A375, M14 and A2058) [133]
α-Thujone and
1,8-cineole
Lung (A549 and NCI-H226) [199]
Leaves 1,8-Cineole Melanoma (C32) and adenocarcinoma (ACHN) [150]
Salvia pisidica Boiss. &
Heldr. ex Benth.
Cultivated
aerial parts
Camphor and
1,8-cineole
Hepatocellular (HepG2 and H1299) [25]
Wild aerial
parts
Camphor,
sabinol and
sabinyl acetate
Hepatocellular (HepG2 and H1299) [25]
Salvia reuteriana Boiss. Aerial parts Labdane
diterpenoids
Cervical (HeLa) and breast (MCF-7) [200]
Salvia rubifolia Boiss. Aerial parts ɣ-Muurolene Melanoma (M14) [152]
Salvia sclarea L. Aerial parts Linalyl acetate Leukemia (HL-60 and K562), breast (MCF-7) and
ovarian (A2780)
[149]
Leaves Not reported Cervical (HeLa) [151]
Salvia verbenaca L. Cultivated
and wild
aerial parts
Hexadecanoic
acid
Melanoma (M14) [101]
Salvia viscosa Jacq. Aerial parts Caryophyllene
oxide
Melanoma (M14, A2058 and A375) [141]
Satureja bachtiarica
Bunge
Leaves Phenol and
thymol
Breast (MDA-MB-231) and ovary (SKOV3) [201]
Satureja hortensis L. Leaves and
owers
Carvacrol Leukemia (K562) [97]
(Continued)
10 L. S. S. D. MESQUITA ET AL.
various cancer cell lines through diverse pathways and can be used in combination with
cancer therapy to decrease the side eects of drugs.
[19,20]
According to literature reports mentioned in Table 1, several cell lines have been
checked to investigate the anticancer activity as a function of EOs under analyses. A
study with Ocimum basilicum (one of the most studied species for popular use) showed
that linalool is the major component of EOs and demonstrated its antitumor potential in a
model with Ehrlich ascites carcinoma cells.
[142]
Kathirvel and Ravi
[143]
showed that O.
Table 1. (Continued).
Plant Species Plant part
Major
constituents Cancer type (Cell Line Used) Reference
Satureja intermedia C.A.
Mey.
Aerial parts Thymol Esophageal squamous cell (KYSE30) and bladder
(5637)
[156]
Satureja khuzistanica L. Aerial parts Carvacrol Colon (SW480), breast (MCF-7) and
choriocarcinoma (JET3)
[202]
Satureja montana L. Aerial parts Carvacrol Lung (A549) [203]
Leaves Thymol Cervical (HeLa) and lung (A549) [148]
Leaves and
owers
α-Terpineol Leukemia (K562) [97]
Satureja parnassica
Heldr. & Sart. ex Boiss.
Aerial parts Carvacrol and
thymol
Breast (MCF-7), lung (A549) and hepatocellular
(HepG2 and Hep3B)
[155]
Satureja thymbra L. Leaves α-Pinene and
p-cymene
Melanoma (C32) and adenocarcinoma (ACHN) [150]
Carvacrol and
thymol
Breast (MCF-7), lung (A549), hepatocellular
(HepG2 and Hep3B)
[155]
Sideritis perfoliata L. Leaves β-Phellandrene Melanoma (C32) and adenocarcinoma (ACHN) [150]
Tetradenia riparia
(Hochst.) Codd
Leaves E,E-farnesol Murine melanoma (B16F10), colon (HT29),
glioblastoma (MO59J, U343 and U251), cervical
(HeLa), breast (MCF-7) and hepatocellular
(HepG2)
[160]
Teucrium brevifolium
Schreb.
Aerial parts Spathulenol
and δ-cadinene
Colon (Caco-2), melanoma (C32) and lung (Cor-
L23)
[154]
Teucrium avum L. Aerial parts Caryophyllene
and 4-vinyl
guaiacol
Colon (Caco-2), melanoma (C32) and lung (Cor-
L23)
[154]
Teucrium montbretii
subsp.
heliotropiifolium
(Barbey) P.H.Davis
Aerial parts Carvacrol and
caryophyllene
oxide
Colon (Caco-2), melanoma (C32) and lung (Cor-
L23)
[154]
Teucrium polium subsp.
capitatum (L.) Arcang.
Aerial parts Carvacrol and
caryophyllene
Colon (Caco-2), melanoma (C32) and lung (Cor-
L23)
[154]
Thymus algeriensis Boiss.
and Reut
Aerial parts Thymol Breast (MCF-7), non-small cell lung (NCI-H460),
colon (HCT-15), cervical (HeLa) and hepatocellular
(HepG2)
[129]
Thymus broussonettii
Boiss
Leaves and
stems
Carvacrol Ovarian (IGR-OV1) [204]
Thymus lanceolatus Desf. Aerial parts Thymol Leukemia (HL-60), breast (MCF-7), hepatocellular
(HepG2), colon (Caco-2) and cervical (HeLa)
[205]
Thymus serpyllum L. Aerial parts Thymol Breast (MCF-7), non-small cell lung (NCI-H460),
colon (HCT-15), cervical (HeLa) and hepatocellular
(HepG2).
[129]
Thymus vulgaris L. Aerial parts Thymol Oral cavity squamous cell (UM-SCC1) [206]
Thymol Breast (MCF-7), non-small cell lung (NCI-H460),
colon (HCT-15), cervical (HeLa) and hepatocellular
(HepG2)
[129]
Commercial
source
Not reported Lung (A549), prostate (PC-3) and breast (MCF-7) [187]
Zataria multiora Boiss. Leaves Phenol and
thymol
Breast (MDA-MB-231) and ovary (SKOV3) [201]
FOOD REVIEWS INTERNATIONAL 11
basilicum oil rich in methyl cinnamate and linalool has antitumor potential against human
cervical cancer (HeLa) and human laryngeal epithelial carcinoma (HEp-2) cell lines. The
dose- and time-dependent antiproliferative activities of O. basilicum EO have been
atributed to the high content of monoterpenes (α-terpinol-59.78%).
[144]
The Rosmarinus ocinalis (rosemary) EOs mainly consist of monoterpenes (1,8-
cineol - 38.5%) and exhibited antiproliferative activity against breast cancer and
hormone-dependent prostate carcinoma cells lines.
[145]
Studies carried out with
supercritical rosemary extracts demonstrated that substances comprising the volatile
oil fraction (1,8-cineol, camphor, borneol, verbenone and bornyl acetate) might
synergize with carnosic acid and inhibited the proliferation of human hepatoma
cells.
[146]
Wang et al.
[147]
assessed the comparative anticancer activities of R. oci-
nalis EOs and three of its main components (1,8-cineole, α-pinene and β-pinene).
They found that rosemary EOs exhibited the strongest cytotoxic activities toward
ovarian (SK-OV-3 and HO-8910) and hepatocellular (Bel-7402) cancer cell lines
with highest activity poseessed by α-pinene followed by β-pinene and 1,8-cineole.
Studies with Salvia lavandulifolia EO rich in camphor showed low anticancer potential
against human cervix carcinoma (HeLa), lung adenocarcinoma (A549) cells. It is worth
noting that S. lavandulifolia presented a half maximal inhibitory concentration (IC
50
)
value of 131.50 μg/mL for human fetal lung broblast cells (MRC-5), which was higher
than the values observed in tumor cell lines studied.
[148]
In a previous study, Foray
et al.
[149]
also detected camphor as main volatile constituent in S. lavandulifolia and
reported its cytotoxicity on tumor cells using cultures of dierent human tumor cell
lines. In the same study, α-thujone was identied as predominant component in S.
ocinalis EO, which was less active on the cell inhibition than S. lavandulifolia. Loizzo
et al.
[150]
demonstrated that S. ocinalis EO inhibited renal adenocarcinoma cell growth.
But 1,8-cineole, the most abundant constituent in S. ocinalis EO, was inactive against the
cell lines used in this study. However, the sesquiterpene fraction characterized by the
presence of α-humulene could be responsible for anticancer action, because this com-
pound demonstrated a strong cytotoxic activity on the human prostate carcinoma
(LNCaP) cells. Russo et al.
[133]
found α-thujone, camphor, borneol, γ-muurolene, and
sclareol in S. ocinalis samples grown under dierent environmental conditions and the
percentages of these compounds varied depending on environmental factors. They also
studied their eect as growth inhibition and pro-apoptotic when evaluated in human
melanoma cell lines, A375, M14, and A2058. A study by Foray et al.
[149]
with S. sclarea
shows predominance of linalyl acetate and linalool as well as the strong activity of this EO
in cultures of dierent human tumor cell lines, equivalent to that of doxorubicin. In vitro
assay with S. sclarea EO showed the ability to inhibit growth of HeLa cells after 24 hours
of treatment in dose-dependent manner.
[151]
Studies carried out in EOs obtained from native and cultivated samples of S. verbenaca
depicted hexadecanoic acid as main constituent with expressive toxicity in a model of
melanoma (M14 cells).
[101]
Caryophyllene oxide was found to be a major constituent in S.
aurea, S. judaica, S. viscosa
[133]
, and S. bracteata.
[152]
It has been evaluated in vitro in a
human melanoma model using M14 cells and caspase-3 activity,
[133]
which suggested the
potential of EO in induction of apoptosis. The EOs of Dracocephalum surmandinum
exhibited cytotoxicity against human breast adenocarcinoma (MCF-7) and erythromyelo-
blastoid leukemia cell lines (K562) with IC50 values of 14 and 16 μg/mL, respectively. The
12 L. S. S. D. MESQUITA ET AL.
main constituents of Eos, Perilla aldehyde and limonene, have been reported to inhibit cell
growth in a dose- and time-dependent manner with IC50 values ranged from 0.25 to
5.0 mmol/L.
[153]
In genus Teucrium, spathulenol and δ-cadinene have been reported as major con-
stituents of EOs in T. brevifolium, caryophyllene and 4-vinyl guaiacol in T. avum,
carvacrol and caryophyllene oxide in T. montbretii ssp. heliotropiifolium, carvacrol and
caryophyllene in T. polium ssp. capitatum. A cytotoxic potential was demonstrated in a
model with colorectal adenocarcinoma (CACO-2), amelanotic melanoma (C-32), and
large lung carcinoma (COR-123) cells. Cytotoxic activity was demonstrated in all cell
lines tested, namely CACO-2 (T. brevifolium <T. montbretii ssp. heliotropiifolium <T.
polium ssp. capitatum), C-32 (T. montbretii ssp. heliotropiifolium <T. polium ssp.
capitatum), and COR-123 (T. montbretii ssp. heliotropiifolium <T. avum (=T. polium
ssp. capitatum)<T. brevifolium).
[154]
Thymol, an EO component found in dierent species of Satureja viz., S. thymbra, S.
intermedia, S. montana, and S. parnassica, has evidenced the potential of EO from
these plant species in treating dierent types of cancer, such as melanoma, adenocar-
cinoma, mammary adenocarcinoma, non-small cell lung adenocarcinoma and hepato-
cellular carcinoma, human oesophagus squamous cell carcinoma and human bladder
carcinoma.
[148,150,155,156]
S. khuzistanica EO was characterized by a high amount of
carvacrol (92.87%) and signicantly reduced cell viability of human colon cancer
(SW480), human breast cancer (MCF-7), and choriocarcinoma (JET 3) cells in a
dose-dependent manner.
EO extracted by distillation from Mentha spicata showed cytotoxicity in human mouth
epidermal carcinoma and murine leukemia model.
[157]
In another study by Hussain et al.
[158]
in dierent species of Mentha obtained at dierent harvesting times showed menthol,
piperitenone oxide, and menthone as major components in M. arvensis, M. longifolia,and
M. piperita, respectively. They also investigated cytotoxicity of these compounds in breast
cancer and hormone-dependent prostate carcinoma and reported that both chemical com-
position and cytotoxicity vary depending on the period of collection of the plant samples.
Nikolicetal.
[148]
performed studies with M. piperita and M. pulegium showing menthol and
pulegone as major constituents of EO in these species, respectively. They noted the low
cytotoxic potential of these oils in models of human cervix carcinoma (HeLa), lung
adenocarcinoma (A549), and human fetal lung broblast (MRC-5).
It is important to analyze the safety of plant species widely used in popular practice. A study
performed by Pathania et al.
[159]
for evaluating the chemotherapeutic potential of Monarda
citriodora demonstrated that its EO and thymol inhibited the cell viability of various human
cancer celllines (including prostate cancer (PC-3), breast cancer (MDA-MB-231 and MCF-7),
lung cancer (A549), and premyelocytic leukemia (HL-60)) in a concentration-dependent
manner and found to be non toxic in normal breast epithelial fR2 cells. The IC
50
values
were between 17 and 74 μg/ml and 10 and 45 μg/ml for EO and thymol, respectively. Thymol
exhibited higher cytotoxicity than EO in all the cell lines mentioned above except in human
leukaemia HL-60 cells. This could be due to the synergism between thymol and other
constituents in EO.
Oliveira et al.
[160]
in a study with EO of Tetradenia riparia identied (E,E)-farnesol and
aromadendrene oxide as major compounds and evaluated their antiproliferative eect in
dierent tumor cell lines (murine melanoma, colon adenocarcinoma, glioblastoma, cervical
FOOD REVIEWS INTERNATIONAL 13
adenocarcinoma, breast adenocarcinoma, and hepatocellular carcinoma). They reported
IC
50
values greater than 30 μg/mL for all cell lines tested and more cytotoxic to normal
line (Chinese hamster lung broblasts).
Shakeri et al.
[161]
reported 4aα,7α,7aβ-nepetalactone as the major constituent of
Nepeta sintenisii essential oil, demonstrating dose-dependent cytotoxicity against tumor
cell lines (ovarian, colon, and breast cancer) but also found toxicity, although low (IC
50
219 μg/mL) in human umbilical vein endothelial cells used as a normal cell line.
It is worth emphasizing that although several studies have reported cytotoxic potential
of the EO from plant species of Lamiaceae, according to American National Center
Institute, only extracts with IC
50
values <30 μg/mL against tumor cells should be the
targets in investigation of new anticancer agents.
[162]
In this perspective, interesting results were obtained with EO of Hyssopus ocinalis
(linalool),
[163]
Lavandula angustifolia,
[164]
M. citriodora (thymol),
[165]
N. sintenisii
(4aα,7α,7aβ-nepetalactone),
[161]
Nepeta ucrainica (germacrene D),
[165]
O. basilicum
(α-terpineol),
[144]
S. verbenaca (hexadecanoic acid),
[101]
S. aurea, S. judaica and S.
viscosa (caryophyllene oxide).
[141]
In vitro culture and EOs production in family Lamiaceae
In vitro culture is one of the important strategies for rapid mass propagation and
conservation of elite germplasm under controlled conditions.
[10,166172]
It can be used
for large-scale multiplication of EOs bearing plants without their overexploitation from
natural resources. In vitro cultures also oer an alternative for enhanced production of
EOs from several plant species. For instance, in Zataria multiora, EOs from in vitro
propagated plants were observed to contain higher amount of carvacrol, thymol, carvacrol
methyl ether and γ-terpinene as compared to wild grown plants.
[166,173]
Content and composition of EOs varies depending on the type and growing stage of
plant material.
[174,175]
The composition of hydrodistilled essential oil from aerial and
underground parts as well as tissue culture raised shoot and adventitious root of
dierent Caryopteris species as analyzed by gas chromatography-mass spectrometry
revealed the highest EOs yield (1.8% V/DW) in Caryopteris xclandonensis.
[174]
Aerial
parts were characterized mainly by the presence of limonene and cedrol (11.916.0 and
10.710.9%, respectively), whereas 3,5-bis (1,1-dimethyl)-phenol (12.926.2%) was the
main component of volatile fractions of the in vivo roots in all the species. 1,8-Cineole
(24.834.2%) and 1-octen-3-ol (19.731.5%) has been reported to be the dominating
volatile constituent of the EOs obtained from in vitro shoots and adventitious root
cultures, respectively. Qualitative and quantitative variations in EOs obtained from
wild and micropropagated plants have also been reported in Z. multiora. In vitro
propagated plants produced essential oil richer in oxygenated sesquiterpenes than wild
grown plants.
[173]
It is quite possible to stimulate quantitative and qualitative modications on the
production of plant secondary metabolites by manipulating nutrient medium and culture
conditions.
[176]
There are dierent factors aecting the production of secondary metabo-
lites from plant cells under in vitro conditions. Some of these are discussed in the
following sections.
14 L. S. S. D. MESQUITA ET AL.
Plant growth regulators
The type and concentration of plant growth regulators (PGRs) used in culture medium
inuence the plant growth and composition of secondary compounds including vola-
tiles oils in dierent plant species. Santos-Gomes and Fernandes-Ferreira
[177]
reported
the highest shoot biomass growth and essential oils accumulation with kinetin (2.0 mg/
L) and 2,4-dichlorophenoxyacetic acid (0.05 mg/L) in S. ocinalis.InLavandula
pedunculata, best propagation rates have been achieved on medium supplemented
with 6-benzylaminopurine (0.25 mg/L). The trichomes and essential oils of the in
vitro raised L. pedunculata plants were found to be similar when compared to wild
plants. Two chemotypes, 1,8-cineole/camphor and fenchone type, were characterized.
The composition of monoterpenes was observed to dier depending on the type of
auxininthemediuminAgastache rugosa.
[178]
Pulegone was the single major com-
pound on the growth regulator-free Murashige and Skoog (MS)
[179]
medium with a
small proportion of limonene. In the presence of PGRs in the medium, the hydro-
carbon monoterpene fraction increased to 2050% in in vitro cultures. The emission of
limonene was reported to be lower than α-pinene in the presence of picloram (0.4
μM).
[180]
Another study by Aonso et al.
[180]
in T. vulgaris L. showed that plants
growing in medium containing indole-3-acetic acid (1.0 μM) increased volatile com-
pounds such as thymol by 315%.
Cultivation mode and culture conditions
Plant cells cultured on dierent cultivation media show variation in secondary compounds
production due to dierent physiological and biochemical environment. Cultivation mode
strongly inuenced the production and transport of low molecular weight volatile com-
pounds in Lavandula vera when cultured under three dierent cultivation modes, that is,
shake ask as a free suspension, two-phase systems in the presence of XAD-4 resin, and in
stirred tank 3-L bioreactors.
[181]
In Salvia miltiorrhiza, EOs composition has been observed to depend on the morphol-
ogy, physiological status, and culture conditions. Comparison of EOs obtained from root,
callus, and hairy roots showed that ethyl hexadecanoate was the main component in root
oil, while callus and hairy root cultures possessed 2,5-hexanedione as the major compo-
nent in this plant species.
[30]
Qualitative and quantitative comparison of root, callus, and
hairy roots showed several common constituents. Four compounds (4-methyl-3-penten2-
one, 2,5-hexanedione, ethyl hexadecanoate and (4aS-trans)1,2,3,4,4a,9,10,10a-octahydro-
1,1,4a-trimethyl-7(1-methylethyl)-phenanthrene) were identied in the root oil. Three
compounds 4methyl-3-penten- 2-one, 2,5hexanedione and hexachloroethane and
six compounds 2,5-hexanedione, 3-(1ethoxy-ethoxy)-butan-1-ol, 1-methoxy2-propa-
none, borneol, octadecanal, and (4aS-trans)-1,2,3,4,4a,9,10,10a-octahydro-1,1,4a-tri-
methyl-7-(1methylethyl)-phenanthrene have been identied in callus and hairy root
oil, respectively. Callus and hairy root oil exhibited higher antioxidant activity than EO
from root.
[30]
EOs in Mentha species and T. vulgaris were found to enhance in in vitro cultures grown
under ultra high CO
2
levels than in ambient air.
[182]
Thymol in thyme plants grown on
basal medium with sucrose was reported to be 317-fold higher at 10,000 μmol/mol CO
2
FOOD REVIEWS INTERNATIONAL 15
than plants grown at ambient conditions. Thymol levels in T. vulgaris plants grown on
basal medium with CO
2
and sucrose were observed to be 3.9-fold higher as compared to
shoots grown on basal medium with same levels of CO
2
but without sucrose.
[182]
Biotransformation
Biotransformation using an exogenous supply of biosynthetic precursors is one of the
strategies used to improve the accumulation of secondary metabolites in many plant
species. In family Lamiaceae, feeding cis-farnesol to cell suspension cultures of
Pogostemon cablin resulted in the increased production of patchouli alcohol from
19.5 mg/L to 25.5 mg/L.
[183]
Conclusions
From the above literature, it can be concluded that EOs from members of family
Lamiaceae possess anticancer properties and may act as an alternative to discover new
anticancer drugs. Therefore, it is important to perform scientic studies in order to prove
the eectiveness of these drugs in in vitro and in vivo models. It is also necessary to study
anti-proliferative action of these EOs on various cancer cell lines through diverse pathways
so as to use them in combination with cancer therapy in order to decrease the side eects
of drugs. To ensure the enhanced production of EOs with active components of interest,
various biotechnological techniques like two-phase culture system, biotransformation, and
genetic modication could be used.
Funding
Authors would like to acknowledge Fundação de Amparo à Pesquisa e Desenvolvimento Cientíco
e Tecnológico do Maranhão (FAPEMA) for nancial support.
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FOOD REVIEWS INTERNATIONAL 27
... Although recent pharmaceutical studies performed on Lamiaceae species were almost exclusively focused on biological activity against various cancer, limited studies have been conducted, comprehensive analysis on the cancer prevention activities of the essential oils of Lamiaceae species Mesquita et al., 2019;Oalđe Pavlovi c et al., 2021). The present study is part of a comprehensive and longterm research including various biological activities of various extracts of Lamiaceae taxa. ...
... Although in previous studies using EOs distilled from different species of Lamiaceae family, the anticancer effects of these EOs have been demonstrated individually towards different cancerous cell and animal models including breast, lung, ovarian, stomach, gastric, liver, glioma, colon, and colorectal cancers, anticancer effects of the EOs distilled from the taxa of Lamiaceae growing in T€ urkiye against various cancer cell lines have not been comparatively examined up to now. (Gezici, 2018;Mesquita et al., 2019;P erez-Gonz alez et al., 2019;Sitarek et al., 2020). Accordingly, the presented research that aimed to reveal cancer prevention potentials of the EOs against NCI-N87, MCF-7, HepG2, and LNCaP clone FGC-Luc2 human cancer cells could be assumed as the first report for the literature. ...
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The present study was aimed to determine phytochemical characterization, anticancer and antioxidant activities of essential oils obtained from 11 Lamiaceae species, including Clinopodium serpyllifolium subsp. barba-tum (P.H.Davis) Br€ auchler, Lavandula angustifolia Miller, Mentha £ piperita L., Mentha pulegium L., Ocimum basilicum L., Rosmarinus officinalis L., Salvia aramiensis Rech.f., Salvia fruticosa Miller, Salvia officinalis L., Satur-eja thymbra L., and Thymbra spicata L. taxa from T€ urkiye. The chemical composition of the essential oils (EOs) was identified using GCÀMS, and antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydra-zyl (DPPH) and 2,2 0-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radical scavenging methods. Furthermore, the anticancer potential of the EOs was evaluated using MTT method against human cell lines, including hepatocellular carcinoma (HepG2), gastric carcinoma (NCI-N87), breast adenocarcinoma (MCF-7), human prostate carcinoma (LNCaP clone FGC-Luc2) cancer cells, and non-cancerous human umbilical vein endothelial cells (HUVECs). The antioxidant activities of the extracts varied from 31.96 to 74.96%. Consistent with antioxidant activities, the anticancer activities of the EOs of S. officinalis, L. angustifolia, and R. officinalis were significantly higher than others. However, almost all EOs were found to inhibit cell viability and induce apoptosis of cancer cells, while the EOs at different concentrations exhibited the highest antican-cer activity against NCI-N87, followed by HepG2, MCF-7, and LNCaP cancer cells, with the IC 50 value ranging from 10.98 § 0.12 to 78.08 § 1.21 mg/mL, respectively. Variability in phytochemical components, free radical scavenging and anticancer activities of EOs was revealed by principal component analysis (PCA) and agglom-erative hierarchical clustering (AHC). The major components of the EOs distilled from Lamiaceae species were found as eucalyptol, thujone, linalool, linalyl acetate, pulegone, carvone and carvacrol at different concentrations in the EOs. Overall, it can be clearly concluded that the EO samples distilled from some medicinal plants belonging to the Lamiaceae family contain valuable phytochemical compounds and accordingly exhibit remarkable biological activities.
... The best-known members of this family are various aromatic spices such as, oregano, mint, thyme, sage, lemon balm, basil, savoury, hyssop, rosemary and others whose use is more limited (Bekut et al., 2018). Species belonging to the Lamiaceae family have anticancer, antioxidant, antiinflammatory, analgesic, antiviral, antitussive, antipyretic, antiasthmatic, antimicrobial, antifungal, antiemetic, antidiabetic, antipruritic, antihypertensive, decongestant, carminative, antinociceptive, antirheumatic, neuroprotective, antidepressant, cholinergic, antiseptic, sedative, antiparasitic, immunomodulatory, anthelmintic, antiallergic, anti-hepatotoxic and antiangiogenic effects have been reported with previous studies (Dhayalan et al., 2015;Carović-StanKo et al., 2016;Uritu et al., 2018;Andrade et al., 2018;Bekut et al., 2018;dos Santos et al.,2018;Cocan et al., 2018;Mesquita et al., 2019;Ouakouak et al., 2019;Luz et al., 2020;Çelik et al., 2021). ...
... Advances in the biological sciences have enabled them to evaluate the therapeutic potential of various plant species (Mesquita et al., 2019). ...
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Bu çalışmada Lamiaceae familyasından seçilmiş bitkilerin (Mentha piperita L., Salvia officinalis L., Lavandula officinalis Mill., Scutellaria orientalis L. ve Melissa officinalis L.) inflamasyon yolağında önemli bir yeri olduğu bilinen lipoksijenaz-12/15 (LOX-12/15), siklooksijenaz-2 (COX-2) ve asetilkolinesteraz (AChE) aktiviteleri üzerine etkileri araştırılmıştır. İnflamasyon sürecinde yan etkileri fazla bulunan inhibitör ilaçlara alternatif olmaları açısından bu bitki ektstelerinin etkinlikleri incelenmiştir. Ekstrelerin metabolomik profilleri GC-MS ve LC-qTOF-MS yöntemleriyle tanımlanmıştır. Ekstrelerin antioksidan potansiyelleri, DPPH+ radikal süpürücü etki ve TAC yöntemleriyle araştırılmıştır. DPPH+ radikalinin zamana bağlı süpürücü etkileri incelendiğinde, ekstrelerin zamana ve konsantrasyona bağlı olarak etkilerinin değiştiği bulunmuştur. Ekstrelerin 12-15-LOX, COX-2 ve AChE enzimleri üzerindeki potansiyel inhibitör etkileri incelenmiş ve elde edilen sonuçların metabolomik profilleri korelasyon analizi ile karşılaştırılmıştır. Elde edilen sonuçlar, ekstrelerin potansiyel anti-inflamatuar ajanlar olarak kullanıma sahip olduğunu düşündürmektedir.
... The Lamiaceae (Labiatae) family, known as "lumbase nilcols" in Asian countries, stands out as a rich source of essential oils extensively utilized in the food, pharmaceutical, and cosmetic industries. These plants are characterized by secondary metabolites with antibacterial, antifungal, antioxidant, anti-inflammatory, and antiviral properties (Mesquita et al., 2019;Mamangkey et al., 2023). Typically, endophytic bacteria produce these secondary metabolites, utilizing plant cells as a source of nutrition. ...
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The rise of multidrug resistance among microorganisms, where they develop resistance against formerly effica-cious drugs, has led to increased disease prevalence and mortality rates, posing a growing challenge. Globally, antibiotic resistance has made a significant impact, causing millions of fatalities each year. Endophytic fungi have gained considerable attention in research due to their potential to produce a wide variety of secondary metabo-lites, including natural substances with antimicrobial capabilities. The genera Aspergillus and Penicillium stand out as the most prevalent species of endophytic fungi. Filamentous fungi, such as these are responsible for the production of 45% of known microbial metabolites. This review focuses on exploring the bioactive substances produced by endophytic fungi from these two genera, particularly in conjunction with medicinal plants. Emphasis is placed on their antimicrobial activity and their ability to inhibit multidrug-resistant pathogens. As the need for alternative treatments to combat drug-resistant infections continues to grow, endophytic fungi have the potential to provide a valuable source of bioactive molecules for medical applications.
... Plants produce chemically diverse compounds that can be used in multitude of ways such as flavour enhancement (Schwab et al., 2008;Malik et al., 2023), as agricultural chemicals (Dayan et al., 2009) and more importantly as herbal medicines (Abiri etal., 2018;Chagas et al., 2015;Makhzoum and Hefferon, 2022;Mesquita et al., 2018;Venkataraman et al., 2019). Hence, they are of vast applicability in different industrial sectors e.g., pharmaceuticals, nutraceuticals, cosmetics, and textiles. ...
Article
Abstract Hairy root culture is one of the promising biotechnological tools to obtain the stable and sustainable production of specialized metabolites from plants under controlled environment conditions. Various strategies have been adopted to enhance the accumulation of bioactive compounds in hairy roots yet their utilization at the commercial scale is restricted to only a few products. Recently, nanotechnology has been emerged as an active technique that has revolutionized the many sectors in an advantageous way. Elicitation using nanoparticles has been recognized as an effective strategy for enhancing the bioactive compounds of interest in plants. Nanoparticles elicit the activity of defense-related compounds through activation of the specific transcription factors involved in specialized metabolites production. This review discusses the recent progress in using nanoparticles to enhance specialized metabolite biosynthesis using hairy root culture system and the significant achievements in this area of research. Biotic and abiotic elicitors to improve the production of bioactive compounds in hairy roots, different types of nanoparticles as eliciting agents, their properties as dependent on shape, most widely used nanoparticles in plant hairy root systems are described in detail. Further challenges involved in application of nanoparticles, their toxicity in plant cells and risks associated to human health are also envisaged. No doubt, nanoparticle elicitation is a remarkable approach to obtain phytochemicals from hairy roots to be utilized in various sectors including food, medicines, cosmetics or agriculture but it is quite essential to understand the inter-relationships between the nanoparticles and the plant systems in terms of specifics such as type, dosage and time of exposure as well as other important parameters.
... Essential oils are complex mixtures of various bioactive compounds, predominantly consisting of terpenoids, phenolic compounds, and other volatile organic compounds. These natural constituents have demonstrated diverse biological activities, such as antimicrobial [5][6][7][8], anti-inflammatory [9][10][11], antioxidant [4,[12][13][14], and anticancer properties [15][16][17], among others. Incorporating essential oil main molecules into drug development programs demands a comprehensive understanding of their physicochemical properties, pharmacokinetics, and safety profiles. ...
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Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest Papp (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters.
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Plants produce food sources such as carbohydrates, fats and proteins, as well as secondary metabolites such as terpenes, phenolics and alkaloids with quite different pharmacological effects. Many of the secondary metabolites produced by plants have very different biological activities. Although the amounts of these compounds in plants are usually small, their unique chemical structure contributes greatly to their pharmacological effects. However, considering the richness of our country's medicinal plant flora and the pharmacological effects of these plants, it can be said that the research on this subject is insufficient. In addition, studies on medicinal plants can be brought to the pharmaceutical industry by purifying natural products with high bioactivity and low side effects at very low cost. Medicinal and aromatic plants are known to have many uses such as food, medicine, cosmetics and spices and have been used for similar purposes since the beginning of human history. The family Lamiaceae is a cosmopolitan family that includes herbaceous, shrub or tree-shaped plants of great economic importance in many parts of the world. In this study, Marrubium trachyticum Boiss. plant, which is an endemic species for our country, belonging to the genus Marrubium selected from the family Lamiaceae, was examined. The phytochemical composition of hexane and methanol:chloroform (1:1) extracts of Marrubium trachyticum were analyzed quantitatively by GC-MS and LC-MS/MS. Antioxidant activities of the plant extracts and inhibitory activities for various enzymes were determined. In addition, molecular docking studies were performed to understand how the phytochemicals may have an effect on tyrosinase, α-amylase and α-glucosidase enzyme activities. Since there are no studies on the phytochemical composition and bioactivities of Marrubium trachyticum, the data obtained from this study will be recorded for the first time.
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Spray drying is a process that involves instantaneous conversion of a liquid or slurry into a free‐flowing powder in the presence of hot air or nitrogen gas current in a drying chamber. The technique is usually used to encapsulate active molecules like essential oils, plant extracts, fragrances, flavours and enzymes within a wall material. The encapsulation provides chemical and physical stability to the actives by converting them into free‐flowing powders which prevents their susceptibility to external atmospheric conditions like temperature, humidity, UV exposure and chemical oxidation. Spray drying encapsulation has an edge over other encapsulation techniques because it is fast, simple, efficient and economically feasible. The article focuses on encapsulating various essential oils within natural polymers and emulsifiers by spray drying methods to form stable microcapsules. The review also provides information on different types of spray drying equipment and process parameters like the type of atomiszer and nozzles, inlet–outlet temperature and type of cyclones. All the process parameters and materials are found to influence the physicochemical properties of the microencapsulates of essential oils. The review also discusses the effects of process parameters and materials on the encapsulation efficiency, moisture content, bulk and tapped density, agglomeration properties and thermal stability of the microencapsulates. Thus, the consolidated review will provide an overview of various optimization parameters and governing factors for obtaining microencapsulates of essential oils.
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Aedes aegyti L. is the main vector of important viruses like Dengue, Yellow, Zika and Chikungunya fevers. In many countries, these diseases are considered as great public health problems due to the serious consequences they can cause such as Guillain-Barré syndrome, neurological disorders and internal hemorrhagic problems, which may lead to death. The transmission of these diseases occurs through the bite of infected female of A. aegypti. According to World Health Organization, the major way to avoid the spread of these diseases is to control the vector by using larvicides and insecticides products. Many efforts have been done to find natural products that can be used to eliminate different phases of the life cycle of this mosquito. Among these, essential oils are recognized as important plant-derived products to control A. aegypti. Essential oils are complex mixture of mono, sesquiterpenes and phenylpropanoids and normally have a nice odor. Several studies have shown the larvicidal and insecticides properties of essential oils in plants belonging to different families. The literature studies indicated that in most of the cases monoterpenes like geraniol and citronellol, and phenylpropanoids; eugenol were the main components of essential oils that can control A. aegypti spread. In vitro studies suggested that composition and production of essential oils could be manipulated by the use of different concentrations and combinations of growth regulators and elicitors.
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Cancer is a major problem of public health and one of the main causes of death around the globe. According to World Health Organization, the prevalence of this disease is rising, however, more rapidly in Africa, Asia, and Central and South America that account for about 70% of cancer deaths in the world. The chemotherapy is one of the ways to treat this disease and the advances in anticancer drugs have improved patient care. Plants have been used to treat different diseases since ancient times. Among the anticancer drugs, about 50% come from natural products as isolated or semisynthetic or related synthetic compounds and plants represent important source of these substances. Taxol, vinca alkaloids, camptothecin, and podophyllotoxins, as well as their semisynthetic or synthetic derivatives, are the most important anticancer drugs obtained from plants. In this chapter, we review the importance of plants as source of drugs and describe these anticancer compounds. The continuing search for antitumor agents from plants is extremely necessary to find the possible ways to have safe and more effective treatment for this health problem.
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Taxol is amongst the most effective anti-cancer drugs available in market. The increasing demand of this compound due to its use in treating wide range of cancers, as well as its high cost have triggered efforts to find alternative ways to obtain this drug. Hazel (Corylus avellana), which is already cultivated for nutritional aspects, is now attracting attention for its phytochemical content. Notably the discovery of taxol and related taxanes in this plant species prompted extensive interest to explore biotechnological production of these compounds using in vitro cultures of C. avellana. This review emphasizes the potential of C. avellana cells for production of taxol and related taxanes. The botanical description of C. avellana, its pharmacological uses and various biotechnological approaches, such as micropropagation, cell culture and genetic engineering to increase the production of taxol and related taxanes are discussed. To present an overall overview, the experience of researchers working on these aspects is mentioned and major highlights or discoveries are presented. A review of the literature suggests that C. avellana may act as a commercial and alternative source for taxol production in an eco-friendly way, which will meet the ever-increasing demand, and also help reducing the cost of this anti-cancer compound.
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E. ciliata (Lamiaceae) is very interesting and promising herb mainly for chemical composition and pharmacological activities. The aim of this study was to determine chemical composition of the essential oils of fresh, frozen and dried herbal materials of E. ciliata and compare different extraction methods This is the first study on composition of E. ciliata volatile compounds from fresh, frozen and dried herbal samples. The samples were prepared by hydrodistillation (HD), extraction with polar solvent-ethanol (ESE) and dynamic headspace solid-phase micro extraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC–MS) method. A total of 48 compounds were identified by GC–MS. Dehydroelsholtzia ketone, elsholtzia ketone, sesquiterpenes β-bourbonene, caryophyllene, α-caryophyllene, germacrene D and α-farnesene were identified and found to be predominant compounds in SPME composition of the fresh, frozen and dried herbal samples. The major amounts of ketones (dehydroelsholtzia and elsholtzia) were determined in dried herbal samples where they made up 24.94% (p < 0.05) and 71.34% (p < 0.05) of the SPME composition. Artemisia ketone was determined only in fresh herb. No previous report exists regarding this ketone in E. ciliata fresh, frozen and dried herbal materials or essential oil. There were 26 components identified in the essential oil obtained by HD. The main compounds of this essential oil were dehydroelsholtzia ketone (78.28%) and elsholtzia ketone (14.58%).
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Essential oil of rosemary was obtained by supercritical CO2-extraction (SCE), hydrodistillation (HYDRO), and steam distillation (SD). Quantity of oil, antioxidant activity, and chemical composition (gas chromatography-mass spectrometry, GC-MS) of the essential oils were evaluated. For SCE, oil was obtained at two temperatures (40 and 50 °C) and two pressures (10.34 and 17.24 MPa) using a rosemary particle size of 600±50 μm. The yield was between 1.41 and 2.53 g essential oil (EO) 100 g⁻¹ of dry rosemary (% w/w). The antioxidant activity values were in the range 29.67-37.55 mg equivalent of Trolox (ET) g⁻¹ of EO or 22.66-30.81 mg ascorbic acid (AA) g⁻¹ of EO. Yields of essential oil were between 0.35 and 2.35%. The antioxidant activity was found in the range 1.73-2.60 mg ET g⁻¹ of EO or 1.50-2.20 mg AA g⁻¹ of EO. Camphor, eucalyptol, β-caryophyllene, and borneol acetate were the main chemicals detected by GC-MS in EO.
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The chemical composition and pharmaceutical properties of thyme essential oil have been of great interest to researchers and food industries. The aim of the present study was to evaluate the effects of seasonal variation on the composition and antimicrobial and antioxidant activities of the essential oil of Thymus vulgaris, as well as to determine the activity of the main pure compounds. Composition of the essential oil was determined by GC/MS. Antioxidant activity of the essential oil and the pure compounds was tested by DPPH, ABTS, and FRAP methods. Antimicrobial activity of essential oil and pure compounds was evaluated by determination of minimum inhibitory concentration. The major compounds of all tested samples were thymol (38.99–52.92%), p-cymene (14.38–26.58%), γ-terpinene (10.43–19.09%), linalool (2.39–3.56%), and carvacrol (1.87–3.3%). The essential oil gathered in October/2012 showed the highest antioxidant activity and strongest antimicrobial activity against S. Aureus (MIC = 20 μg/mL), E. Coli (MIC = 50 μg/mL) and S. typhimurium (MIC = 500 μg/mL). Furthermore, the above sample contained the highest amount of thymol. Regarding the analyses of pure compounds, only thymol and carvacrol showed free radical scavenging capacity, and strong antimicrobial activity, while thymol was the most effective against S. Aureus (MIC = 250 μg/mL), E. Coli (MIC = 120 μg/mL) and S. typhimurium (MIC = 60 μg/mL). Data suggested the spring time (around 20 °C in Brazil) as the appropriate season to collect the essential oil from thyme.