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Essential Oils: Extraction Techniques, Pharmaceutical And Therapeutic

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DOI: 10.2174/1389200219666180723144850

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Current Drug Metabolism, 2018, 19, 000-000 1

REVIEW
ARTICLE

Essential Oils: Extraction Techniques, Pharmaceutical And Therapeutic Potential - A

Review
Zarith Asyikin Abdul Aziz1, Akil Ahmad1,2,3, Siti Hamidah Mohd Setapar1,4,5,*, Alptug Karakucuk6,
Muhammad Mohsin Azim2, David Lokhat2, Mohd. Rafatullah3, Magdah Ganash7, Mohammad A.
Kamal8,9,10 and Ghulam Md Ashraf 8,*
1
Centre of Lipid Engineering and Applied Research (CLEAR), Ibnu Sina Institute for Scientific and Industrial Research, Universiti
Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia; 2Department of Chemical Engineering, University of KwaZulu-
Natal, Durban 4041, South Africa; 3School of Industrial Technology, Universiti Sains Malaysia, Penang-11800, Malaysia; 4Faculty
of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia; 5SHE Empire Sdn
Bhd., Bandar Baru Kangkar Pulai, 81300 Skudai, Johor, Malaysia; 6Gazi University, Faculty of Pharmacy, Department of Pharma-
ceutical Technology, Etiler 06330, Yenimahalle, Ankara, Turkey; 7Department of Biology, Faculty of Science, King Abdulaziz Uni-
versity, Jeddah, Saudi Arabia; 8King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 9Enzymoics,
7 Peterlee Place, Hebersham, NSW 2770; 10Novel Global Community Educational Foundation, Australia
Abstract: Background: Essential oils are liquid extracts from aromatic plants, which have numerous applications in
multiple industries. There are a variety of methods used for the extraction of essential oils, with each method exhibit-
ing certain advantages and determining the biological and physicochemical properties of the extracted oils. Essential
oils from different plant species contain more than 200 constituents which are comprised of volatile and non-volatile
components. The application of essential oils as antimicrobial, anticancer, anti-inflammatory and anti-viral agents is
due to their effective and efficient properties, inter alia.
ARTICLE HISTORY Methods: Several advanced (supercritical fluid extraction, subcritical extraction liquid, solvent-free microwave ex-
Received: October 11, 2017 traction) and conventional (hydrodistillation, steam distillation, hydrodiffusion, solvent extraction) methods have
Revised: February 05, 2018 been discussed for the extraction of essential oils. Advanced methods are considered as the most promising extrac-
Accepted: May 29, 2018 tion techniques due to less extraction time, low energy consumption, low solvent used and less carbon dioxide emis-
DOI: sion.
10.2174/1389200219666180723144850
Conclusion: This manuscript reviewed the major research studies in the field and discussed several research findings
on the chemical composition of essential oils, methods of oil extraction, and application of these oils in pharmaceuti-
cal and therapeutic fields. These essential oils can be used as anticancer, antimicrobial, antiviral, and as skin permea-
tion enhancer agents.
Keywords: Essential oils, chemical compositions, method of extractions, pharmaceutical, therapeutic potentials.

1. INTRODUCTION Additionally, several essential oils genres are characterized in a

Essential oils as defined by the European Pharmacopeia 7th
edition [1] are “Odorant products, which have the complex compo-
sition, and obtained from plant raw extract, either extracted by
steam of water, dry distillation or a suitable mechanical method
without heating. Generally, a physical method is used for the sepa-
ration of essential oil from the aqueous phase which has no signifi-
cant change in its chemical composition”. Multiple segments of the
oils’ plants such as peels, barks, leaves, flowers, buds, seeds, and
others are used to produce these aromatic oily liquids, and various
extraction techniques are applied for the extraction process [2].
Essential oils are lipophilic, and soluble in organic solvents, due to
their hydrophobic nature and lower density than water. The extrac-
tion yields are dependent on the type of species and plant segments
used, but a very low yield like 1%, can make them highly valuable
rare components [1]. Amongst the plethora of aromatic plants spe-
cies, only 10% out of 17,000 plant species considered as aromatic [3].
*Address correspondence to these authors at the Centre of Lipids Engineer-
ing and Applied Research, IbnuSina Institute for Industrial and Scientific
Research, Universiti Teknologi Malaysia, 81310 UTM Skudai, Johor, Ma-
laysia; Tel: +607-5535496; Fax: +607-558 8166; E-mail: sitihami-
dah@cheme.utm.my
King Fahd Medical Research Center, King Abdulaziz University, P. O. Box
80216, Jeddah 21589, Saudi Arabia; Tel.: +966126401000; E-mails: ash-
raf.gm@gmail.com, gashraf@kau.edu.sa
small number of families: Lauraceae, Lamiaceae, Asteraceae,
Myrtaceae, Rutaceae, Cuppressaceae, Poaceae, and Piperaceae [4].
The differences between essential oils’ chemical properties are
not only based on their number and type of molecules, but also on
their stereochemical structures, which can be varied by selected
extraction process method. The quality, quantity, and composition
of extracted essential oils can be altered according to plant organ,
age, soil composition, climate change, and cycle stages of plant life
[5]. Additionally, the essential oils are commonly known as plant
secondary metabolites which contain complex mixtures of volatile
organic compounds such as terpenes and sesquiterpenes (hydrocar-
bon group), and alcohols, ethers, esters, ketones, aldehydes, phe-
nols, lactones, and phenol ethers (oxygenated group) [6].
Generally, all kind of essential oils has two or three major com-
ponents with the highest concentrations (20%-70%) compared to
the other components present in trace amounts. For example, in
Oraginum species, the essential oil contains 30% of carvacol and
27% of thymol as major components. These components determine
the biological properties of these aromatic oils, whereas each of
them is included in different groups of distinct biosynthetical ori-
gin. Terpenoids, phenylpropanoids, and short-chain aliphatic hy-
drocarbon derivatives are the main specific groups for some con-
stituents in essential oils [6]. Fig. (1) represents the typical struc-
tures of essential oils’ constituents.

1389-2002/18 $58.00+.00 © 2018 Bentham Science Publishers

2 Current Drug Metabolism, 2018, Vol. 19, No. 00
Monoterpenoids Sesquiterpenoids
OH
OH
HO
Limonene Thymol Carvacrol B-bisabol
Phenylpropanoids
OH O classified as non-volatile residues [11].
O method is used for determining constituents present in essential
O oils. This method is simple, allows fast responses, is efficient, and
Eugenol Myristicin
H3CO
CH3
CH3
OCH3 OCH3
trans-anethole cis-anethole
Fig. (1). Typical structures of essential oil constituents [6].
Interest in the application of essential oils in various fields is
increasing continuously, and with their significant pharmacological
activities, these aromatic medicinal plants are being implemented in
pharmaceutical industries as antibacterial, anti-inflammatory, anti-
viral, and antifungal agents. Various studies have been conducted to
examine the antimicrobial activities of essential oils against multi-
ple bacteria [1-3]. Furthermore, psychiatrists use essential oils for
their psychic patients due to the amiable odor formed by the aro-
matic plant's oils [7].
Furthermore, the demand for essential oils as food preservatives
is growing because of their biological action against food-borne
pathogens such as Salmonella typhimurium, Clostridium perfrin-
gens, Listeria monocytogenes, Pseudomonas putida, and Staphylo-
coccus aureus [8]. The problem of pathogens in food and meat
products has been addressed by low dosage application of essential
oils, as demonstrated by numerous researches [9].
There has been an increased demand for the use of natural
plants as an alternative to conventional antibiotics in animal feed
due to the development of antibiotic-resistant bacteria and their
possible transmission from livestock to humans. Indeed, the use of
synthetic antibiotics in livestock feed has been prohibited by the
European Union in order to promote the healthy growth of animals
[10].
In pharmaceutical industries, medicines in the form of capsules,
syrups, ointments, creams, and sprays contain some compositions
of essential oils and their production numbers are constantly grow-
ing. Thus, the applications of essential oils in numerous fields;
food, pharmaceutical, and cosmetic industries are still being inves-
tigated in order to formulate and produce more efficient essential
oil-based products. This review covers in detail the extraction proc-
Aziz et al.
ess involved in producing essential oils and their compositions, and
also their pharmaceutical and therapeutic potentials as antimicro-
bial, antiviral, anticancer, and as skin permeation enhancer agents.
2. CHEMICAL COMPOSITIONS OF ESSENTIAL OIL
There are more than 200 components present in pure essential
oils which are normally mixtures of terpenes, and phenylpropanoid
derivatives, in which the chemical and structural differences be-
tween compounds are minimal. The constituents of essential oils
may be broadly classified as volatile and non-volatile fractions. The
overall chemical composition of the aromatic oil volatile fraction
includes mono- and sesquiterpene components, and several oxy-
genated derivatives along with alcohols, aliphatic aldehydes, and
esters. On the other hand, 1-10 wt% of isolated essential oil com-
prises carotenoids, fatty acids, flavonoids and waxes which are
Generally, Gas Chromatography-Mass Spectrometry (GC-MS)
is a broadly used analytical technique for the determination of es-
sential oils constituents. A GC-MS report is the fingerprint of any
particular batch of essential oil. The unique properties of the oils
can be deduced from its chemical composition and GC-MS is able
to indicate the purity of essential oils in most cases [12]. The com-
ponents of essential oils are delineated below.
2.1. Hydrocarbons
Hydrocarbon is a chemical compound found in essential oils
with their building blocks connected by hydrogen and carbon bond-
ing [13]. An example of basic hydrocarbons found in essential oils
is isoprene as shown in Fig. (2).
Isoprene
Fig. (2). Chemical structure of isoprene.
2.1.1. Terpenes
Mono-, sesqui-, and diterpenes are categorized under the terpe-
nes’ group. Monoterpene is the result of combining two isoprene
units, depicted in Fig. (2), from head to tail, whereas sesquiterpenes
are formed if three isoprenes join together, while diterpenes struc-
tured from four linked isoprene units [14].
2.1.1.1. Monoterpenes
The main properties of monoterpenes are anti-bacterial, analge-
sic, stimulant, and expectorant. Monoterpenes are naturally occur-
ring constituents in essential oil plants with the majority being un-
saturated hydrocarbons (C10). Alcohols, ketones and carboxylic
acids are present as substituents in the oxygenated derivatives of
monoterpenes, which are collectively known as monoterpenoids
[13]. Fig. (3) shows the components comprising monoterpenes. The
branched-chains of C10 hydrocarbons, forming a linkage of two
isomers, are widely distributed in herbal plants with more than 400
naturally occurring monoterpenes identified [15].
OH
Limonene Menthol
Fig. (3). Chemical structures of (a) Limonene and (b) Menthol.
Pharmaceutical & Therapeutic Role of Essential Oils
2.1.1.2. Sesquiterpenes
Sesquiterpenes are biogenetically isolated from farensyl pyro-
phosphate, an intermediate in both the mevalonate and non-
mevalonate pathways used by organisms in the biosynthesis of
terpenoids, sterols, and terpenes. The structures of sesquiterpenes
may be linear, monocyclic or bi- and tricyclic. Linear structures of
sesquiterpenes, referred to as farnesenes, are branched hydrocar-
bons with four double bonds [16].
The farnesenes usually found in essential oils are E,E-
-
farnesene and E--farnesene, while E,Z-
-farnesene and Z,Z-
-
farnesene are not reported to occur in nature. Farnesols is a primary
alcohol in oxidation products of farnesenes, as well as E- and Z-
nerodiol as tertiary alcohol are occasional essential oil constituents.
The aldehydes components of farnesenes consist of
-sinensal and
-sinensal, where they occur as minor components in essential oils
from various Citrus species [17].
In monocyclic compounds of sesquiterpenes, there are
bisobolenes groups with C6 ring structures, and their isomers such
as Z-
-bisabolene, -bisabolene, E--bisabolene, and Z--
bisabolene which occur in several essential oils. Besides,
-
Zingiberene, -Curcumene, and ar-curcumene also found in ses-
quiterpenes group of essential oils.
-Zingiberene is the main com-
ponent inside ginger essential oil (Zingiber officinale) and the pun-
gent smell of this oil is due to the aromatic structure, gingerol (phe-
nols). -Curcumene is the main constituent found in Curcuma oils
(Curcuma aromatic and Curcuma longa), while the aromatic
-
curcumene usually found in Curcuma and Zingiber species [17].
The bicyclic bergamotenes represent a structure like the pine-
nes, i.e. a cyclobutane ring. In the lemon essential oil and lodgepole
pine (Pinuscontorta), Trans-
-bergamotene occurs as a minor con-
stituent, while Pimpinella affinis occurs as a major component. -
Caryophyllene (E-caryophyllene) derived from
-humulene pre-
sents a C9 ring fused to a cyclobutane ring. It is broadly found as a
major component in the essential oils from cannabis, oregano, and
rosemary, and also found in the vegetative parts of many plants. -
Caryophyllene selectively binds to the CB(2) receptor so that it acts
as a functional CB(2) agonist. Additionally, through in vivo study,
this natural constituent exerts cannabimimetic effects with anti-
inflammatory action [18].
2.1.1.3. Diterpenes
These constituents are made up from combining four units of
isoprene. They are considered as too heavy components which do
not evaporate easily during the extraction process using steam dis-
tillation; hence, it is impossible to be found in isolated aromatic
oils. Diterpenes are found in all plant families with C20 chemical
structures. Almost 2500 known diterpenes were discovered which
belong to 20 major structural types. Diterpenic derivatives can be
found in plant hormones and phytol, where they occur as a side
chain on chlorophyll [19].
2.2. Alcohols
Alcohols in essential oils provide some excellent properties like
anti-septic, anti-viral, anti-bacteria, and germicidal. Alcohols natu-
rally occur as a single component or combined with a terpene or
ester. The attachment of terpenes with oxygen and hydrogen atom
can result in the formation of alcohols. The term Monoterpenol is
used to describe a monoterpene that contains hydroxyl groups in-
side its hydrocarbon structure. Alcohols are considered safe to be
used since their amounts are extremely low or totally absent of
toxic reaction in the body or onto the skin [20].
2.3. Esters
The formation of esters 

Current Drug Metabolism, 2018, Vol. 19, No. 00 3
to provide anti-inflammatory activities. In medical sciences, esters
are considered to have antifungal and sedative properties, with bal-
ancing action on the nervous system. They are generally free from
precautions with the exception of methyl salicylate found in birch
and wintergreen which is toxic within the system [17].
The common esters found in essential oils are linyl acetate and
geranyl formate which are present in bergamot and lavender, and
geranium essential oils [17].
2.4. Ketones
Ketones have anti-catarrhal, cell proliferant, expectorant, and
vulnerary properties and are often found in plants that are used for
upper respiratory tract complaints. Essential oils with ketone group
are advantageous for wound healing and improve scar tissue. Thu-
jone is a very toxic ketone component that exists in sage, mugwort,
thuja, tansy, and wormwood essential oils. Besides, pulegone is
another toxic ketone component found in essential oils such as
pinocamphone and pennyroyal oils [17].
Other than that, jasmone, fenchone, carvone and menthone are
the non-toxic ketone components found in jasmine oil, fennel oil,
spearmint and dill oil, and peppermint oil [17].
3. EXTRACTION METHODS FOR ESSENTIAL OILS
Several parts of various aromatic plants can be extracted and
form essential oils which subsequently have many applications in
cosmetics, pharmaceutical and food safety fields. The manufactur-
ing method and technique used to extract essential oils are depend-
ent on the characteristics and components required in the botanical
extract. The main factor to ensure the quality of essential oils is the
extraction method used, since inappropriate extraction procedures
may cause the destruction and vary the action of phytochemicals
present in aromatic oils. The resulting effects can be, for example,
the loss of pharmacological constituents, stain effect, off-
flavor/odour, and physical change of essential oils [2].
Such extraction techniques can be categorized into two catego-
ries: classical methods and innovative methods. The application of
innovative techniques, such as ultrasonic and microwave enhanced
processes, has improved the efficiency of extraction process in
terms time required for isolation of the essential oil and energy
dissipation, as well as improvement in production yield, and high
quality of essential oils [1].
3.1. Conventional Extraction Methods
Conventional techniques applied to extract essential plant oils
are based on water distillation by the heating process.
3.1.1. Hydrodistillation
Hydrodistillation is the oldest and simplest oils extraction
method which was discovered by Avicenna and the first to develop
extraction through the alembic. Rose was the first plant extract used
and purified by this method. The procedures start with immersing
the plant materials directly into water inside the alembic (vessel),
and whole mixture was boiled. The devices include a heating
source, vessel (Alembic), a condenser to convert vapor from vessel
onto liquid, and a decanter to collect the condensate and to separate
essential oils with water (Fig. 4).
This extraction technique is considered as a unique method to
extract plant materials like wood or flower and is frequently used
for extractions involving hydrophobic natural plant material with a
high boiling point. As the oils are surrounded by water, this method
is able to protect essential oils to be extracted at a certain degree
without being overheated. The main advantage of this extraction
technique is its ability to isolate plant materials below 100°C [1].



 



Few studies have been conducted on the extraction of essential
is due to the interaction between alcohols and acids. The ester com- plant oils by using hydrodistillation. Okoh et al. investigated the
ponent inside essential oils offers soothing and balancing effects. comparison between extraction process, Hydrodistillation (HD) and
Due to the presence of alcoholic groups inside esters, they are able Solvent-free Microwave Extraction (SFME) on the properties and
4 Current Drug Metabolism, 2018, Vol. 19, No. 00
Fig. (4). Flow diagram of hydrodistillation extraction process [1].
yield of essential oil from rosemary (Rosmarinus officinalis L.).
Through hydrodistillation, a total yield of the volatile fraction was
0.31%, while 0.39% was obtained for the SFME method [21].
The general hydrodistillation process has been modified by
using new technologies as reported by a few researchers. Gol-
makani and Rezaei developed advanced HD extraction process
technique named Microwave-assisted HD (MAHD) which showed
superiority in energy dissipation and isolation period (75 min com-
pared to 4 h in HD) [22]. Additionally, Ohmic-assisted HD
(OAHD) is the other advanced HD extraction technique, discovered
by Gavahian and co-workers. Through OAHD, thyme essential oil
can be extracted in a period of only 25 min compared to HD
method. No change was observed in characteristics of components
in thyme obtained by OAHD and HD [23].
3.1.2. Steam Distillation
In essential plant oil extraction, steam distillation method is the
broadest technique applied. The percentage of essential oils being
extracted by this technique is 93% and the remaining 7% can be
further extracted by other methods [24]. Basically, the process
started by heating of plant material using steam which is supplied
from steam generator (Fig. 5). Heat is the main factor determining
how effectively the plant material structures break down and burst
and release the aromatic components or essential oils [25].
Masango developed an innovative steam distillation extraction
technique to increase the isolated essential oil yields and reduce the
amount of wastewater produced during the extraction process. The
system uses a packed bed of the plant samples, placed above the
steam source. Only steam is allowed to pass through the plants and
boiling water does not mix with the botanical materials. Therefore,
the process requires less steam and the amount of water in the
distillate can be reduced [24].
In another study, Yildirim et al. reported a component 2,2-
diphenyl-1-picryl hydrazyl (DPPH) used to evaluate the antioxidant
properties of essential oils by using steam distillation extraction
process. It was reported to have a higher yield of antioxidant com-
ponents than the oils extracted by hydrodistillation (HD) [26].
3.1.3. Hydrodiffusion
Hydrodiffusion extraction method is an extraction process in
which steam is supplied to a container which holds plant materials.
This technique is only applied on dried plant samples that can be
damaged at boiling temperature. In the steam distillation process,
steam is applied from the bottom of the steam generator, whereas in
Aziz et al.
the hydrodiffusion method, steam is supplied from the top of the
generator. This process was carried out at low pressure or vacuum
and steam temperature can be reduced below 100°C [27].
This steam diffusion method was further enhanced by adding
microwave technology. Bousbia and research team have investi-
gated the difference in performance between innovative Microwave
Hydrodiffusion and Gravity (MHG) and a traditional method like
hydrodistillation [28]. In another study, the isolation of essential oil
from orange peel was studied using an innovative steam diffusion
technique (SDf) called microwave steam diffusion (MSDf). The
extraction performance results showed that the isolation period of
the essential oils by MSDf technique is within 12 minutes and had
similar yield and aromatic profile to those obtained by SDf for 40
minutes [28].
3.1.4. Solvent Extraction
Ordinary solvents like acetone, petroleum ether, hexane,
methanol, or ethanol have been implemented by this technique to
extract fragile or delicate flower materials which cannot be ex-
tracted using heat or steam supplied [2]. Generally, the plant sam-
ples are mixed with solvents to be extracted by mildly heating the
mixture, and the process is followed by filtration and evaporation of
the solvents. The filtrate contains a resin (resinoid), or the mixture
of wax, fragrance, and essential oil. Alcohol is combined with the
filtrate mixture in order to dissolve the essential oil into it and
thereafter distilled at low temperature. During the distillation proc-
ess, the alcohol absorbs fragrance and is evaporated while the aro-
matic absolute oil remains in the pot residue. Compared to other
methods, this method is more complicated for essential oils extrac-
tion, and as a result, time-consuming and more expensive [29].
In another study, authors investigated the antioxidant activity of
Ptychotisverticillata by solvent extraction technique for essential
oils extraction. It was found that 48% of phenolic compounds are
present and contain 44.6% and 3.4% of carvacol and thymol, re-
spectively, as the main compounds [30]. In other studies, the essen-
tial oils were separated from Thymus praecox subsp. Skorpilii var.
Skorpilii (TPS), and its chemical constituents and antioxidant activ-
ity were investigated by mixing the plant extractant with different
solvents like ethanol, methanol, and water. These extracts showed
significant free-radical scavenging activity with 40.31% of thymol
and 13.66% of o-cymene. The results also showed that the extrac-
tion process using water as the solvent gives highest phenolics and
flavonoids compared to other types of solvents [31].
Pharmaceutical & Therapeutic Role of Essential Oils Current Drug Metabolism, 2018, Vol. 19, No. 00 5

Fig. (5). Diagrammatic illustration of steam distillation method [2].

the final product since CO2 easily reverts to a gas under normal
3.2. Innovation of Extraction Methods
atmospheric pressure and temperature [16].
The further modification of extraction techniques is due to vari-
Several plant materials have been extracted by using supercriti-
ous disadvantages of conventional methods which encourage essen-
cal carbon dioxide extraction method such as rose geranium,
tial oils to undergo chemical alteration like hydrolysis,
Eugenia caryophyllata, clove buds, and marchantia convolute, and
isomerisation, and oxidation. These processes involve high tem-
their chemical constituents are revealed by some researches [17, 19,
perature and affect the quality of essential oils, at the same time
20, 37]. In a study about the comparison between supercritical fluid
prolonging the extraction period. In the field of essential oils extrac-
extractions with hydrodistillation method, by using the supercritical
tion process, it is very important to maintain the oils chemical con-
fluid technique, an essential oil was successfully isolated and re-
stituents and natural proportion at its original state. The parameters
vealed as advance aromatic oil, with superior performance and
that need to be considered in new extraction techniques are reduc-
pharmacological activities [25]. Other than that, a carrot essential
tion of extraction period, energy consumption, solvent used and
oil obtained by supercritical fluid extraction method was found to
carbon dioxide emission [1].
give better antibacterial and antifungal properties against Bacillus
3.2.1. Supercritical Fluid Extraction cereus as compared to the oil obtained by hydrodistillation [38].
Conventional extraction techniques such as solvent extraction 3.2.2. Subcritical Extraction Liquid
and steam distillation need more time to undergo the extraction
The use of water at subcritical state has been reported by many
process and a large amount of organic solvents are required [32].
researchers and found that this is a better and powerful alternative
Additionally, the disadvantages of these techniques like various
of essential oils extraction technique [39]. The definition of
volatile components losses, poor efficiency of oils extraction, deg-
subcritical stage of liquid is the time when liquid reaches pressure
radation of unsaturated compounds, and toxic residues from extrac-
higher than the critical pressure, Pc and lower than the critical tem-
tion process need to be encountered [33, 34].
perature, Tc or vice-versa. The fluids that are used to extract essen-
The supercritical fluid state is mainly depending on two factors tial oils using this method are water and CO2. The subcritical state
which are the fluids critical pressure, Pc and critical temperature, of fluid offers several superior characteristics such as lower viscos-
Tc. Fluids with these critical parameters exhibit very interesting ity, lower density, and enhanced diffusivity between gas and liq-
properties such as low viscosity, high diffusivity, and density closer uids. This extraction technique is considered the best alternative
to liquids [1]. Carbon dioxide is used as a supercritical solvent for approach as it enables a fast essential oil isolation process, con-
the extraction of essential oils due to its numerous attractive proper- ducted at a low working temperature. Moreover, it is a cost-
ties: (i) easily reach critical point (low critical pressure, Pc : 72.9 efficient extraction, simple and environmental friendly process [39].
atm, and temperature, Tc : 31.2°C); (ii) unaggressive for thermo
In this process, the required duration of extraction is only
labile molecules of the plant essence; (iii) chemically inert and
15min compared to 3h required to extract essential oils by using
toxic; (iv) nonflammable; (v) available in high purity at relatively
conventional methods. Essential oils with more valuable properties
low cost; (vi) easily eliminated; (vii) its polarity similar to pentane
which are a higher amount of oxygenated components with no sig-
which makes it suitable for extraction of lipophilic compounds [35,
nificant presence of terpenes can be obtained and allow substantial
36].
cost saving in terms of both energy and plant materials [2].
Generally, the principle of supercritical fluid extraction process
Kubatova and co-workers investigated the lactones extraction
involves the use and recycling fluid in repeated steps of compres-
from a Piper methysticum root by using subcritical water extrac-
sion/decompression. The supercritical state of CO2 can be achieved
tion, and this method was compared with Soxhlet extraction with
by highly compressing and heating this fluid. Then, it passes
water. The working temperature for subcritical water extraction was
through the raw plant material to load volatile matter and plant
at 100°C and 175°C, and the extraction time required to extract the
extracts. The process is followed by decompression steps, where the
lactones was 20 min and 2h, respectively. Soxhlet extraction
mixture of CO2 and plant extracts are routed to two separators
method showed a large difference in extraction time compared to
where the fluid is gradually decompressed to separate the obtained
subcritical water method, and required 6 hours to extract the oils
extracts from the CO2. The CO2 is released from second separator
and produced lower yields by 40% to 60% [40].
and recycled into storage tank, and no solvent residue remains in
6 Current Drug Metabolism, 2018, Vol. 19, No. 00
3.2.3. Solvent Free Microwave Extraction
The impediments of ordinary extraction techniques, such as
solvent and hydrodiffusion, are the losses of several evaporative
constituents, poor isolation coherence, and toxic solvent residues at
the final product stage. These challenges prompted the considera-
tion of Solvent-Free Microwave Extraction (SFME) for various
applications [28]. This technique is an expeditious isolation of es-
sential oils from spices, aromatic herbs, and dry seeds. Several ad-
vantages of SFME have been reported by researchers, which can be
summarized: to obtain essential oils with high yield and selectivity,
shorter extraction time, and environmentally friendly process [28].
SFME involves a combination of two techniques which are
heating plant samples using microwave technology followed by dry
distillation which operates at an atmospheric pressure in the ab-
sence of any solvent. Bayramoglu et al. applied SFME method to
extract oregano at different microwave power; 622W, 498W,
373W, and 249W, while the essential oil yields were determined
depending on each different microwave power used. The results
showed maximum yields achieved at 0.054, 0.053, 0.052 and 0.049
mL/g of oregano essential oil at 622W, 498W, 373W, and 249W
power levels, respectively. Exception with working at lowest mi-
crowave power (249W), all other yields were found to be higher (p

0.05) [41]. Compared to hydrodistillation, the yield extracted
oregano essential oil was only 0.048 mL/g which about 6% slightly
lower than SFME oregano oil highest yield. Later, Ferhat et al.
presented the comparison of SFME method with traditional meth-
ods in terms of extraction periods, yields, impact of the technique
used towards the environment, solvent residues content, and antim-
icrobial activities. It was demonstrated that microwave extraction
offers a shorter isolation period of essential oil (30 min compared to
3 h for hydrodiffusion and 1 h for cold pressing); 0.24% of yields
from SFME which is much better than hydrodiffusion and cold
pressing with 0.21% and 0.05%, respectively; high energy con-
sumption for performing hydrodiffusion and cold pressing (using
mechanical motors) compared to rapid microwave extraction; no
water and solvent used in SFME make the extraction process as
cleaner features, and high antimicrobial activities of essential oils
obtained by SFME technique [42].
4. PHARMACEUTICAL AND THERAPEUTIC POTEN-
TIALS OF ESSENTIAL OILS
The implementations of essential oils in pharmaceutical fields
are broadly discussed and investigated by numerous scientists, par-
ticularly their function as anticancer, antimicrobial, antiviral, and as
skin permeation enhancer agents. Outlines of previous findings are
discussed in the subsections that follow.
4.1. Essential Oils and Cancer
Initially, essential oils have been identified and applied for the
treatment of inflammatory and oxidative diseases. The oils react
with oxygen species that have been linked to the origin of oxidation
and inflammation that can lead to cancer, and this shows that essen-
tial oils have also the ability to be an anticancer agent [43].
The formation of cancer by oxidative and inflammatory dis-
eases results from oxidative stress causing damage to cell DNA and
effectively increase the process of cells mutating and thus leads to
oncogenic transformation.
Furthermore, oxygen radicals derived from the oxidative stress
react with other cell molecules and activate signaling pathways and
thus, encourage the tumor development through the regulation of
cellular angiogenesis, proliferation, and metastasis [44]. Hence,
chronic inflammation is linked to several steps of cancer formation
such as carcinogenesis, promotion, survival, proliferation, angio-
genesis, and metastasis [45]. Some studies have shown the applica-
tion of various essential oils as chemotherapeutic agents of various
types of cancer.
Aziz et al.
4.1.1. Prostate Cancer
Essential oils extracted from Hypericumhircinum L. subsp.
Majus have been demonstrated to give anti-proliferative activity on
human prostate cancer. Throughout the study, this essential oil was
tested in vitro using MTT assay in order to investigate their ability
to inhibit tumor cell growth on human glioblastoma (T98G), human
squamous carcinoma (A431), human prostatic adenocarcinoma
(PC3), and mouse melanoma (B16-F1). The performance of this
essential oil as an anti-proliferative agent was compared with cis-
platin, a typical chemotherapeutic drug used [46]. The results
showed that the essential oil was moderately inhibiting the tumor
cell growth. The highest activity was recorded on the A431 cell
line, while the lowest activity was observed on the PC3 cell line.
Besides, Essien et al. investigated the cytotoxic study of
Solanium erianthum, solanium macranthum of fruit and leaf vola-
tile essential oils on human breast and prostate cancer cells, HS
578T, and PC-3, respectively [47]. According to the results found,
it can be seen that S. erianthum leaf oil exhibited in vitro inhibitory
effect against human breast cancer cells. Other than that, the results
showed that S. macranthum leaf oil has no ability to inhibit the
growth of both types’ cancer cells.
In another study, in vitro cytotoxicity of essential oil against
three different tumor cells; OVCAR-8, human ovarian cancer cell;
NCI- H358M, human lung cancer cell; and PC -3M human prostate
cancer cell was investigated from the leaves of Xylopia frutescence
using thiazolyl blue test (MTT) assay. It was reported that Xylopia
frutescence essential oil obtained IC50 values ranging from 24.6 and
40.0 g/mL for cancer cell lines of NCI-H358M (lung carcinoma
cell) and PC-3M (prostate carcinoma cell), respectively. Doxorubi-
cin, a common chemotherapeutic drug as a positive control, showed
the IC50 value of 0.9 and 1.6 g/mL for same cell lines [48]. There-
fore, the essential oil is promising for future anti-cancer drug devel-
opment in accordance to Suffness and Pezzuto who described that
the essential oils with IC50 values below 30 g/mL can be used in
anticancer drugs [49].
Later, in vivo cytotoxicity of Lavender angustifolia essential oil
against prostate cancer cell line was evaluated by Zhao et al. Male
nude mice were inoculated subcutaneously into the rear flanks part
with human prostate cancer cell line (PC-3). The mice were
grouped into 4 and treated with subcutaneous injections of solvent
control, lavender essential oil, Linalool, and linalyl acetate. In each
treatment, a dose of 200 mg/kg was injected twice a week for 4
weeks onto tumor part of the mice. The tumor growth was meas-
ured twice a week with a caliper, and tumor volume was calculated.
According to the result, the lavender essential oil (P < 0.001),
Linalool (P < 0.001), and linalyl acetate (P = 0.016) showed signifi-
cantly inhibited xenograft tumor growth, compared to the control
group. Therefore, this study concluded that the extracted Lavender
Angustifolia essential oil was effective in inhibiting tumor growth
of prostate carcinoma cell in nude mice [50].
4.1.2. Breast Cancer
Various studies have been carried out by researchers to investi-
gate the cytotoxic activity of essential oils to inhibit breast cancer
cells. A study was conducted by Fogang and co-workers, where the
in vitro biological properties, cytotoxic activities of seed essential
oils from bush onion (Afrostyrax lepidophyllus) and tropical garlic
tree (Scorodophloeus zenkeri) was investigated. The cytotoxic
study of these essential oils was conducted by using MTT assay. In
this study, four cancer cell lines were examined, which are T98G
human glioblastoma, MDA-MB 231 human breast adenocarcinoma,
A 375 human malignant melanoma, and HCT116 human colon
carcinoma cell lines [51]. The S. zenkeri oil was found to be slightly
more active compared to A. lepidophyllus oil. This essential oil
showed the highest potential for inhibition of tumor cell growth for
MDA-MB 231 and HCT116 with IC50 values 8.0 and 8.5 g/mL,
respectively.
Pharmaceutical & Therapeutic Role of Essential Oils
Furthermore, cytotoxic activity of aromatic and medicinal plant
from Madagascar, Cedrelopsisgrevei essential oil was investigated
by Afoulous et al. The cancer cell line examined by the aromatic
plant was MCF-7, human breast cancer cell. The essential oil re-
vealed a conspicuous effect to inhibit tumor growth on the cell line
MCF-7 with the IC50 value of 21.5 ± 2 mg/L. The cytotoxic analy-
sis of Cedrelopsis grevei essential oil was compared with doxorubi-
cin [52].
4.1.3. Lung Cancer
Xylopia frutescens Aubl. (Annonaceae), an essential oil ex-
tracted from a medicinal plant of Central and South America, Af-
rica and Asia has been studied and applied to inhibit tumor growth
of NCI-H358M known as human lung cancer cell lines. In this
study, in vivo antitumor effect of this essential oil was conducted by
implanting tumor lung cancer cell (2  106cells per 500 μL) subcu-
taneously into the left hind groin of mice. Then, 5% DMSO dilution
of essential oil was given to mice intraperitoneally, once a day for 7
consecutive days [48]. There were four groups of mice; Group 1:
animals treated with injection of vehicle 5% DMSO (control)
(n=15); Group 2: animal treated with injection of 5-fluororacil (5-
FU, 25 mg/kg/day) (positive control) (n = 9); Group 3: animal
treated by injection of essential oil (50 mg/kg/day) (n = 8); Group
4: animal treated by injection of essential oil (100 mg/kg/day) (n =
8). These treatments were carried out onto mice a day after tumor
injection, while on day 8, the animals tumors were excised and
weighed. The study reported that the mean average tumor weight of
control group was 1.93 ± 0.13 g. The injection of 50 and 100 mg/kg
Xylopia frutescens essential oil onto mice tumor resulted in 1.33 ±
0.19 g and 1.20 ± 0.10 g of average tumor weight, respectively.
Besides, positive control group showed the reduced tumor weight
by 63.2%, with 31.0-37.5% of tumor growth inhibition. Thus, the
study demonstrated Xylopia frutescens essential oil exhibit antican-
cer properties, however, further investigations are recommended to
establish the mechanism involved in the anticancer activity of es-
sential oil [48].
In another study of cytotoxicity of essential oils, Rashid and co-
workers investigated in vitro cytotoxic activity of medicinal plant
essential oil extracted from Artesimia indica wild against four hu-
man cancer cells, A-549 (lung), THP-1 (leukemia), Caco-2 (colon),
and HEP-2 (liver). The procedure of this analysis was conducted by
using sulphordomanie - B assay. The concentration of essential oil
was varied from 10 to 100
g/mL and this reduced the viability of
the four cell lines [53]. The percentage of the essential oils have
potential to inhibit tumor cell growth in case of A-549 (lung), THP-
1 (leukemia), Caco-2 (colon), and HEP-2 (liver) was revealed to be
72%, 95%, 78%, and 82%, respectively, while the IC50 values of
each examined cancer cell lines were found to be 25
g/mL, 10

g/mL, 19.5
g/mL, and 15.5
g/mL, respectively. Thus, based on
these results, the essential oil has the potential to exhibit significant
cytotoxic activity.
4.2. Essential Oils as Antibacterial Agent
The application of aromatic plants as antibacterial agents to
inhibit bacterial growth and decay prevention has been applied
since ancient times. Scientifically, various studies have reported the
potential of essential oils to prevent bacterial growth in many fields.
4.2.1. Eucalyptus globules essential oil
Antimicrobial activity of Eucalyptus Globulus essential oil
against Escherichia coli (E. coli) and Staphylococcus aureus
(S. Aureus), the bacteria found in environments, foods, intestines,
and respiratory tract was investigated. The extraction process used
to extract the oil was the hydrodistillation technique, and the inhibi-
tory effect of Eucalyptus Globulus essential oil was studied by us-
ing agar disc diffusion and dilution broth method. The results
showed that the essential oil has the potential to inhibit both bacte-
rial activities by varying the size of inoculums and the concentra-
Current Drug Metabolism, 2018, Vol. 19, No. 00 7
tion of essential oil. The largest zone of inhibition was up to 10-
3
dilution of E. Coli with 100% of essential oil concentration and the
smallest zone was obtained by S. Aereus (10-1 dilution) with 25% of
essential oil concentration [54].
The chemical constituents found in eucalyptus extract like 1,8-
cineole, citronellal, citronellol, citronellyl acetate, p-cymene,
eucamalol, limonene, linalool, - pinene, -terpinene, - terpinol,
alloocimene and aromadendrene may be the major causes of the
essential oil ability to inhibit bacterial growth. Since this essential
oil gives a good potential as an antimicrobial agent, it has been
proposed to be a natural antibiotic for the treatment of several infec-
tious diseases, however, further clinical studies should be consid-
ered and recommended [53].
4.2.2. Artemesiaannua. L Essential Oil
An aromatic plant named Artemisia Annua L, a cultivated herb
near Sarajevo extracted by hydrodistillation method. Bosnia has
investigated its function as antimicrobial agent against Gram-
positive bacteria, Staphylococcus aureus ATCC 6538 and ATCC
25923, Bacillus subtilis ATCC 6633, Enterococcus faecalis ATCC
29212, Streptococcus pneumonia ATCC 49619, Micrococcus luteus
ATCC 4698, and Gram-negative bacteria, Escherichia coli ATCC
25922, Pseudomonas aeruginosa ATCC 9027 and ATCC 27853,
Haemophilus influenza ATCC 49766, and fungus Candida krusei
ATCC 6258 by using agar diffusion technique [55]. Results of an-
timicrobial activity of the essential oil (10 mg/mL) were compara-
ble to the antibiotic ampicillin (10 mg/mL), used as a positive
probe, and thymol (10 mg/mL), a popular medicinal plant known
for its antibacterial properties. The data revealed that the Gram-
negative, H. influenza, and the Gram-positive bacteria, S. pneumo-
nia, were the most sensitive strains tested to the oil of Artemisia
annua L with inhibition zones at more than 60 and 50 mm, respec-
tively. Thus, A. annua has the ability to inhibit H. influenza, S.
pneumoniae, M. luteus, and C. krusei microbial strains.
4.2.3. Pelargonium graveolens L'Her and Vitexagnus-castus L
Essential Oils
Pelargonium graveolens L'Her and Vitexagnus-castus are two
herbs with important uses in medicines, foods, and cosmetics
mainly found in Iran. They are distilled volatile oils and have char-
acteristics of pharmacological and biological activities such as anti-
oxidant, anti-influenza, anticancer, antimicrobial, and antifungal
activity [56].
Ghannadi et al. investigated the antimicrobial properties of
these essential oils against six bacterial species which are character-
ized as pathogen and food-borne bacterial pathogens, Listeria
monocytogenes (PTCC 1297), Salmonella enteritidis (PTCC 1091),
Pseudomonas aeruginosa (PTCC 1074), Escherichia coli (PTCC
1330), Staphylococcus aureus (PTCC 1112) and Bacillus subtilis
(PTCC 1023) [35]. The results showed that P. graveolens essential
oil has the ability to inhibit all examined bacterial strains with inhi-
bition zone measurements; E. coli (9.5 ± 0.7 mm), P. aeruginosa
(25.3 ± 1.1 mm), S. aureus (42.0 ± 3.2 mm), B. subtilis (16.5 ± 0.7
mm), S. enteritidis (9.0 ± 0.0 mm) except L. monocytogenes (NE).
The most sensitive strain was S. aureus and this essential oil has
good inhibiting properties for further use in nutraceutical and phar-
maceutical fields. Besides, four examined strains were successfully
inhibited by V. agnus-castus essential oil with reported inhibition
zone; P. aeruginosa (4.0 ± 0.7 mm), S. aureus (50.0 ± 0.0 mm), B.
subtilis (11.0 ± 0.7 mm), S. enteritidis (9.0 ± 0.0 mm) except L.
monocytogenes (NE) and E. coli. (NE). S. aureus was found to be
the most sensitive one to inhibit all bacterial strains [35].
4.2.4. Curcuma aeruginosa (C. aeruginosa), Curcuma mangga
(C. mangga), and Zingibercassumunar (Z. cassumunar) Essential
Oils
These essential oils are among zingiberaceous plants, which are
rarely studied by researchers regarding their antimicrobial activi-
ties. The common species of zingiberaceous which are scientifically
8 Current Drug Metabolism, 2018, Vol. 19, No. 00
proven as antimicrobial agents are the family of ginger (Zingiber
officinale) and turmeric (Curcuma longa) [57].
Othman and co-workers studied the extracted plant oils from
family of zingiberaceous, Curcuma aeruginosa (C. aeruginosa),
Curcuma mangga (C. mangga), and Zingiber cassumunar from
Malaysia, for their antimicrobial activity against four bacteria: Ba-
cillus cereus (B. cereus), Staphylococcus aureus (S. aureus), Es-
cherichia coli (E. coli), and Pseudomonas aeruginosa (P. aerugi-
nosa); and two fungi: Candida albicans (C. albicans) and
Cyptococcus neoformans (C. neoformans), using disc-diffusion
method [58]. The results revealed that three essential oils displayed
a various degree of inhibition against the examined microorgan-
isms. The strongest activity was performed by C. mangga essential
oil, while C. aeruginosa had moderate activity, and Z. cassumunar
resulted in no activity against most of the microorganisms tested.
The most sensitive bacteria were S. aereus, since it was inhibited by
all three essential oils, while P. aeruginosa was known as the most
resistant bacteria since the oils showed either weak or no inhibition
towards it [58].
4.3. Essential Oils as Antiviral Agent
Various infectious diseases are caused by some agents called
viruses, and meanwhile, there are many types of drugs available to
be antiviral agents. Aromatic plants essential oil extracts have been
evaluated for their performance as an antiviral agent, including
essential oils commonly used in culinary applications [59].
4.3.1. Lippia graveolens (Mexican oregano) Essential Oil
This essential oil is a plant of family group of Verbenaceae
which are frequently known as Mexican oregano and used in Mex-
ico as a food seasoning and a folk remedy [60]. The antibacterial
activity of this oil has been revealed, and the inhibition activity of
the essential oil was due to its main constituents, named carvacrol
[61]. In 2011, a study was carried out on the antiviral activity of
Lippia graveolens essential oil and its main component, carvacrol,
against human and animal viruses using MTT test, which conducted
by Alves and research team [62]. The antiviral activity experiment
was conducted to investigate the potential of Lippia graveolens and
its main constituent, carvacrol, against 5 DNA viruses; HHV (hu-
man herpesvirus)-1, ACVR (acyclovir)-HHV 1, BoHV (bovine
herpesviruses)-1, BoHV-2, and BoHV 5. Meanwhile, three RNA
viruses (genetic viruses) which are HRSV (human respiratory syn-
cytial virus), RV (human rotavirus), and BVDV (bovine viral diar-
rhea virus) have also been studied [62].
From the result, Mexican oregano essential oil successfully
inhibited the five out of eight examined viruses, while carvacrol
also inhibited the same viruses as an essential oil, except BoHV 1
and 5. During the pre/post-treatment, where the essential oil added
before and after viral inoculation, the oil showed a good inhibition
of these 5 viruses, while only two of these viruses were successfully
inhibited when the oil added after viral inoculation. However, the
effective performance of the oil before viral inoculation seemed to
make a difference. BVDV was the only one who showed that the
Lippia graveolens essential oil was more efficient when applied
after viral inoculation [62].
4.3.2. Eight Eucalyptus Species’ Essential Oils
The Eucalyptus, a native Australian aromatic plant belonging to
the Myrtaceae family, comprises about 900 species [63]. The vola-
tile oils are contained in the 300 species of Eucalyptus, while less
than 20 species known for their major constituents named 1,8-
cineole (more than 70%) which have been commercially used in
pharmaceutical and cosmetic fields [64]. Since 2007, one Eucalyp-
tus plant known as Eucalyptus globulus has been investigated by
some researchers for its efficacy against Haemophilus influenza and
Stenotrophomonas maltophilla, two well-known bacteria and vi-
ruses causing respiratory infections [65].
Aziz et al.
In 2012, Elaissi et al. studied the application of Eucalyptus
essential oil as an antiviral agent to inhibit the human fungal and
enteroviral infections. Elaissi and co-worker investigated the antivi-
ral activities of the eight types of Eucalyptus essential oils against
coxsakievirus B3 incubated with Vero cell line, a productive repli-
cation of influenza B viruses [66]. The eight species of Eucalyptus
were E. bicostata, E. cinerea, E. maidenii, E. Odorata and E. Si-
deroxylon, collected from Souiniat arboreta located in the North
west of Tunisia; E. astringens and E. Lahmannii collected from
Korbous arboreta; and another species, E. Leucoxylon was collected
from Jbelabderrahman arboreta.
In order to clarify the mode of antiviral action and to identify
the target site, cells were pre-treated with essential oils before viral
infection (cells pre-treatment) and the virus was incubated with
essential oils before cell inoculation (virus pre-treatment). Maxi-
mum non-cytotoxic concentrations were used for all tested samples.
The result showed that there was no inhibition viral infections
among essential oils of E. sideroxylon, E. lehmannii, E. Leucoxylon
and E. Odorata, while essential oils of E. Bicostata and E.
Astringens resulted in a significant antiviral activity with the values
of IC50, 0.7 - 4.8 mg/mL and 8.4 mg/mL, respectively, followed by
E. Cinerea essential oil (IC50
=
102-131
mg/mL) and E.
Maidenni (IC50
=
136.5 - 233.5
mg/mL). The antiviral activities
of these essential oils vary and depend on the doses. The antiviral
activities declined by decreasing the concentration of essential oils
used.
In terms of antiviral performance of the oils in pre-treatment
cells and virus, E. bicostata showed a better antiviral activity at pre-
treatment of the virus with the selectivity index, SI 22.8, which is
better than cell pre-treatment with SI, 3.33 only. Besides, the E.
astringent revealed an antiviral activity only at virus pre-treatment.
Based on these results, no correlation was found between the
chemical composition and the antiviral assay. However, the re-
search proved the ability of Eucalyptus essential oils in inhibiting
virus infections, and the activity of the examined essential oils may
occur due to synergism between the major and minor constituents
[66].
4.4. Essential Oil as Skin Penetration Enhancers for Transder-
mal Drug Delivery
Various fields involved in the application of essential oils are
cosmetics, pharmaceutical, and food industries, whereas their po-
tential as anticancer, antibacterial, antiviral, and anti-inflammatory
agents has been studied and evaluated. Many human diseases have
been reported to be treated with essential oils due to their numerous
biological activities. Therefore, studies have been conducted to
evaluate these aromatic plants as suitable permeation enhancers to
increase the percutaneous absorption of various drugs in topically
administration through the lower skin layer.
4.4.1. Turpentine Essential Oil
In 2011, a study was carried out on the potential use of oil tur-
pentine as a transdermal permeation enhancer to deliver ibuprofen
from hydrogel through the skin. 1% w/v of ibuprofen hydrogels
were formulated with Carboxypoly Methylene (CPM) with and
without turpentine oil. Turpentine oil was added into ibuprofen
hydrogel with different concentration, i.e. 0.5, 1, 1.5, 2, 2.5, and 3%
of the total formulation [67]. In vitro permeation, the study was
conducted with a Franz diffusion cell using excised rabbit abdomi-
nal skin. These results indicated that there was a significant increase
in drug permeation as the concentration of essential oil increased.
From the results, the presence of 3% turpentine oil showed the
greatest effect on Ibuprofen delivery through rabbit skin. Maximum
flux was found at P7 formulation with 17.26 mg/cm2/h across rabbit
abdominal skin. Thus, this study concluded that turpentine oil was
the main cause of the enhancement of Ibuprofen permeation from
hydrogel due to the ease of disruption of stratum corneum. The
primary mechanism of disrupting stratum corneum may increase
Pharmaceutical & Therapeutic Role of Essential Oils
permeation of the drug. Thus, turpentine oil was proved to be a
good natural penetration enhancer for hydrogel formulations [67].
4.4.2. Eucalyptus Essential Oil
Karpanen and co-workers studied the eucalyptus essential oil
incorporated with chlorhexidine digluconate (CHG), as a skin anti-
septic in order to enhance its efficacy during topical application as
skin antiseptic drug. CHG was applied to the surface of donor skin
and its penetration efficacy was examined by using Franz diffusion
cell method [68]. One of the parameters that are manipulated
throughout the experiment was the concentration of eucalyptus
essential oil added into formulations. CHG amount was fixed and
the result of CHG incorporated with essential oil permeation into a
different layer of skin.
From the results, it was shown that 5% of essential oil possess
greater CHG permeation to the deeper layer skin (< 300
m), and
10% of the essential oil enhanced CHG penetration in the upper
skin layer, 900
m. Besides, there was no significant difference in
CHG skin permeation between 10% and 20% amount of essential
oil. Therefore, these results indicated that a combination between
CHG and essential oil was able to enhance skin penetration of CHG
for topically applied as antiseptic agent [68].
4.4.3. Eryngium bungei Essential Oil
There are 9 species comprised under genus Eryngium (Umbel-
liferae), which are usually found in many regions of Iran. Their
leaves are traditionally used in salad or food and also for traditional
medicine as a diuretic agent. In 2009, a study was carried out re-
garding the investigation of this essential oil and its methanolic
extract as permeation enhancer of piroxicam, a NSAIDs used as an
antipyretic agent using Franz diffusion cells system. The formula-
tions were characterized into 3 types; type I: base gel, type II: gel
containing different concentration of extracts (0.5, 1, 1.5, 2, 2.5 and
3 % w/w), and type III: gel containing different concentration of
essential oil (0.25, 0.5, 1, 2, 3, 4 and 5 % w/w) [69]. The results
illustrated that the greatest permeation rate can be achieved when
the concentrations of extract and essential oil increased. Thus, this
study concluded that the enhancement of drug permeation was due
to increased lipid disruption in the stratum corneum and existing of
E. bungei methanol extract and essential oil.
CONCLUSION
This review attempts to highlight the extraction techniques of
numerous essential oils and their potential as anticancer, antiviral,
antimicrobial, and skin penetration enhancing agents, especially in
pharmaceutical fields. The results reviewed by this manuscript are
aimed to attract researchers’ attention to the preparation of alterna-
tive drugs from natural products, as well as examining the pharma-
ceutical diversity of essential oils. The critical analysis of the data
presented attempts to promote the basis for reviving the old art of
essential oils treatment, depending on our contemporary scientific
knowledge of their mode of action. Unfortunately, the lipophilic
nature, propensity for degradation and oxidation and high volatility
of essential oils are considered to be their major limitations, causing
them to be less therapeutic compared to essential oil-based products
in pharmaceutical fields. Hence, in future, new technology ap-
proaches may be considered for creating better delivery methods of
essential oils, to ensure high bioavailability and therapeutic effects.
LIST OF ABBREVIATIONS
BoHV = Bovine Herpesviruses
RV = Human Rotavirus
HHV = Human Herpesvirus
OVCAR = Ovarian Cell Cancer
SFME = Solvent Free Microwave Extraction
MSDf = Microwave Steam Diffusion
HD = Hydrodistillation
Current Drug Metabolism, 2018, Vol. 19, No. 00 9
GC-MS = Gas Chromatography-Mass Spectrometry
HRSV = Human Respiratory Syncytial Virus
BVDV = Bovine Viral Diarrhea Virus
CPM = Carboxypolymethylene
CHG = Chlorhexidine Digluconate
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or other-
wise.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the financial supports
given to this work by Research Management Centre (RMC), grant
no. (Q.J130000.2546.17H02), Universiti Teknologi Malaysia.
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