Downy Lavender Oil: A Promising Source of Antimicrobial, Antiobesity, and Anti-Alzheimer’s Disease Agents

Abstract

Lavandula pubescens Decne (LP) is one of the three Lavandula species growing wildly in the Dead Sea Valley, Palestine. The products derived from the plant, including the essential oil (EO), have been used in Traditional Arabic Palestinian Herbal Medicine (TAPHM) for centuries as therapeutic agents. The EO is traditionally believed to have sedative, anti-inflammatory, antiseptic, antidepressive, antiamnesia, and antiobesity properties. This study was therefore aimed to assess the in vitro bioactivities associated with the LP EO. The EO was separated by hydrodistillation from the aerial parts of LP plants and analyzed for its antioxidant, antimicrobial, anticholinesterase, and antilipase activities. GC-MS was used for phytochemical analysis. The chemical analysis of the EO composition revealed 25 constituents, of which carvacrol (65.27%) was the most abundant. EO exhibited strong antioxidant (IC 50 0.16–0.18 μ L/mL), antiacetylcholinesterase (IC 50 0.9 μ L/mL), antibutyrylcholinesterase (IC 50 6.82 μ L/mL), and antilipase (IC 50 1.08 μ L/mL) effects. The EO also demonstrated high antibacterial activity with the highest susceptibility observed for Staphylococcus aureus with 95.7% inhibition. The EO was shown to exhibit strong inhibitory activity against Candida albicans (MIC 0.47 μ L/mL). The EO was also shown to possess strong antidermatophyte activity against Microsporum canis , Trichophyton rubrum , Trichophyton mentagrophytes, and Epidermophyton floccosum (EC 50 0.05–0.06 μ L/mL). The high antioxidant, enzyme inhibitory, and antimicrobial potentials of the EO can, therefore, be correlated with its high content of monoterpenes, especially carvacrol, as shown by its comparable bioactivities indicators results. This study provided new insights into the composition and bioactivities of LP EO. Our finding revealed evidence that LP EO makes a valuable natural source of bioactive molecules showing substantial potential as antioxidant, neuroprotective, antihyperlipidemic, and antimicrobial agents. This study demonstrates, for the first time, that LP EO might be useful for further investigation aiming at integrative CAM and clinical applications in the management of dermatophytosis, Alzheimer’s disease, and obesity.

Full text

Research Article
Downy Lavender Oil: A Promising Source of Antimicrobial,
Antiobesity, and Anti-Alzheimer’s Disease Agents
Mohammed S. Ali-Shtayeh ,
1
Salam Y. Abu-Zaitoun,
1
Nativ Dudai,
2
and Rana M. Jamous
1
1
Biodiversity and Environmental Research Center (BERC), Til, Nablus, State of Palestine
2
Unit of Medicinal and Aromatic Plants, Newe Ya’ar Research Center, Agricultural Research Organization, Ramat Yishay, Israel
Correspondence should be addressed to Mohammed S. Ali-Shtayeh; msshtayeh@yahoo.com
Received 22 October 2019; Accepted 16 January 2020; Published 7 February 2020
Academic Editor: Attila Hunyadi
Copyright ©2020 Mohammed S. Ali-Shtayeh et al. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Lavandula pubescens Decne (LP) is one of the three Lavandula species growing wildly in the Dead Sea Valley, Palestine. e
products derived from the plant, including the essential oil (EO), have been used in Traditional Arabic Palestinian Herbal
Medicine (TAPHM) for centuries as therapeutic agents. e EO is traditionally believed to have sedative, anti-inflammatory,
antiseptic, antidepressive, antiamnesia, and antiobesity properties. is study was therefore aimed to assess the in vitro bio-
activities associated with the LP EO. e EO was separated by hydrodistillation from the aerial parts of LP plants and analyzed for
its antioxidant, antimicrobial, anticholinesterase, and antilipase activities. GC-MS was used for phytochemical analysis. e
chemical analysis of the EO composition revealed 25 constituents, of which carvacrol (65.27%) was the most abundant. EO
exhibited strong antioxidant (IC
50
0.16–0.18 μL/mL), antiacetylcholinesterase (IC
50
0.9 μL/mL), antibutyrylcholinesterase (IC
50
6.82 μL/mL), and antilipase (IC
50
1.08 μL/mL) effects. e EO also demonstrated high antibacterial activity with the highest
susceptibility observed for Staphylococcus aureus with 95.7% inhibition. e EO was shown to exhibit strong inhibitory activity
against Candida albicans (MIC 0.47 μL/mL). e EO was also shown to possess strong antidermatophyte activity against
Microsporum canis,Trichophyton rubrum,Trichophyton mentagrophytes, and Epidermophyton floccosum (EC
50
0.05–0.06 μL/mL).
e high antioxidant, enzyme inhibitory, and antimicrobial potentials of the EO can, therefore, be correlated with its high content
of monoterpenes, especially carvacrol, as shown by its comparable bioactivities indicators results. is study provided new insights
into the composition and bioactivities of LP EO. Our finding revealed evidence that LP EO makes a valuable natural source of
bioactive molecules showing substantial potential as antioxidant, neuroprotective, antihyperlipidemic, and antimicrobial agents.
is study demonstrates, for the first time, that LP EO might be useful for further investigation aiming at integrative CAM and
clinical applications in the management of dermatophytosis, Alzheimer’s disease, and obesity.
1. Introduction
e genus Lavandula (Lamiaceae), lavender, is a typical
aromatic evergreen understory chamaephyte that comprises
about 32 species [1], some of them being utilized in com-
plementary and alternative medicine for a long time, either
dried or as essential oils (EOs). ree native Lavandula
species are growing wild in Palestine (West Bank and Gaza
Strip), namely, L. pubescens Decne (Downy lavender), L.
stoechas L. (French lavender), and L. coronopifolia Poir.
(Staghorn lavender) [2]. L. pubescens is common in the Dead
Sea Valley, Jerusalem, and Hebron Desert and very rare in
the Lower Jordan Valley and L. coronopifolia is common
only in the Dead Sea Valley and only rare in Jerusalem and
Hebron Desert, whereas L. stoechas is rare in Gaza Strip.
Many pharmacological properties have been reported for
lavender EOs, including local anesthetic, sedative, analgesic,
anticonvulsant, antispasmodic [3, 4], cholinesterase inhib-
itory [5], antioxidant [6, 7], antibacterial, and antifungal
effects and inhibition of microbial resistance [6, 8], and they
are used for the treatment of inflammation and many
neurological disturbances [9]. e oil has also been utilized
Hindawi
Evidence-Based Complementary and Alternative Medicine
Volume 2020, Article ID 5679408, 10 pages
https://doi.org/10.1155/2020/5679408

for relieving anxiety and associated sleep disorders [10],
depression, and headache [11]. e EO of Lavandula species
is also used widely in pharmaceutical fragrance, food, and
household cleaners [12–14].
e EO of L. pubescens has been reported to exhibit a
strong wide-ranging in vitro antibacterial activity against
Gram-positive and Gram-negative bacteria including Sal-
monella enterica,Staphylococcus aureus,Micrococcus luteus,
Enterococcus faecalis, and Escherichia coli [6, 13, 15] and
hepatoprotective [16], cytotoxic, and xanthine-oxidase in-
hibitory activities [6, 8].
e products derived from the Palestinian Downy lav-
ender (L. pubescens) (Arabic, Khuzama), including EO, have
been utilized for centuries in Traditional Arabic Palestinian
Herbal Medicine (TAPHM) as CAM therapies [17]. e LP
EO is traditionally believed to have sedative, anti-inflam-
matory, antiseptic, antidementia, and antiobesity properties
and has therefore been utilized for the management of, but
not limited to, indigestion, neurological disorders, dementia,
obesity, and microbial skin infections [17].
However, no reports are available on the anti-
dermatophytic, anticholinesterase (i.e., anti-Alzheimer’s
disease), and antilipase (i.e., antiobesity) effects associated
with the EO of L. pubescens.
is study was, therefore, aimed at defining the chemical
composition of EO attained from above-ground parts of L.
pubescens plants collected from wild populations in the Dead
Sea Valley in Palestine, and assessing its potential in vitro
antioxidant, antimicrobial, anticholinesterase, and antilipase
effects and thus to verify its use as a complementary
medicine for the treatment of AD, obesity, and microbial
skin infections.
2. Materials and Methods
2.1. Plant Material and Essential Oil Extraction. e aerial
parts of fully bloomed Lavandula pubescens were collected
from Palestine (Dead Sea Valley) in May 2017 and used for
EO extraction. Plants were authenticated by the first author.
e voucher specimen (Lavandula pubescens Decne,
Voucher No. BERC-BX603) has been deposited at BERC
Herbarium, Til, Nablus, Palestine. 250gm of the fresh above-
ground plant parts were subjected to hydrodistillation using
a modified Clevenger apparatus until there was no signifi-
cant increase in the amount of EO collected [18].
2.2. GC-MS Analysis of Essential Oil. Gas chromatography-
mass spectrometry (GC-MS) was performed to determine
the EO composition by using the conditions reported by Ali-
Shtayeh et al. [18]. Identification of the compounds was
performed by comparing their relative retention indices (RI)
with those of authentic compounds (e.g., carvacrol, terpi-
nolene, ε-caryophyllene, and β-bisabolene) or by comparing
their mass spectral fragmentation patterns with Wiley 7 MS
library (Wiley, New York, NY, USA) and NIST98 (Gai-
thersburg, MD, USA) mass spectral database. e identified
components along with their RI values and percentage
composition are summarized in Table 1.
2.3. Antioxidant Activity Evaluation. Antioxidant properties
of the EO from L. pubescens were evaluated by using the
following methods: the 2,2′-azino-bis (3-ethylbenzo thia-
zoline-6-sulphonic acid) ABTS radical cation decolorization
and reductive potential (RP) assays as reported previously
[19, 20]. Trolox, ascorbic acid, and BHT were used as
standard antioxidants.
2.4. Enzymatic Inhibitory Activities. e essential oils of L.
pubescens and carvacrol were investigated for their enzyme
inhibitory properties on acetylcholinesterase (AChE),
butyrylcholinesterase (BuChE), and porcine pancreatic li-
pase (PPL) following previously reported spectrophoto-
metric methods [21, 22]. Neostigmine was used as a
reference compound for AChE and BuChE enzymes, and
orlistat was used for PPL enzyme.
e effects of different doses of test compounds (LP
essential oil, carvacrol and reference compounds) on the
AChE, BuChE, and PPL activities were used to calculate
the IC
50
values from dose-effect curves by linear
regression.
2.5. Microbiological Assays. Microorganisms used in this
study are presented in Table 2.
2.5.1. Agar Disc Diffusion Assay. is method was used to
evaluate the antimicrobial activities of the EO and carvacrol
against Candida albicans and bacterial strains as described
by the Clinical and Laboratory Standards Institute (CLSI)
[23]. e inhibition zone diameter for each sample was
measured in mm and used to calculate the antibacterial and
anticandidal activity index (AI) and % of inhibition (PI) at a
concentration of 1 μL/disc using the following formulas [24]:
AI �mean zone of inhibition of EO
zone of inhibition obtained for standard antibiotic ,
PI �AI ×100%.
(1)
All experiments were done in triplicate. Chloram-
phenicol and voriconazole were used as positive controls for
bacteria and candida, respectively.
2.5.2. Broth Microdilution Assay. e broth microdilution
technique with some modifications was used to determine
the minimum inhibitory concentration (MIC) values of the
EO against bacteria and C. albicans strains [25–27].
Chloramphenicol (1 to 64 μg/mL) and voriconazole (0.019 to
1.25 μg/mL) were used as reference antibiotics for bacteria
and Candida, respectively.
2.5.3. Determination of Antidermatophytic Activity: Poi-
soned-Food Technique. Essential oils from L. pubescens and
carvacrol were tested for their antidermatophyte activity
against four dermatophytes species: Microsporum canis,
Trichophyton mentagrophytes,Epidermophyton floccosum,
2Evidence-Based Complementary and Alternative Medicine

and Trichophyton rubrum (Table 2) using the modified
poisoned-food technique [28]. EO and carvacrol were
tested at different concentrations (0.5–0.0039 mL/L).
Mycelial growth inhibition % (PI) was calculated as
follows:
%PI �DC −DT
DC
􏼢 􏼣×100,(2)
where DC is the average diameter of mycelial growth of the
control, and DT is the average diameter of mycelial growth
Table 1: Chemical composition of the essential oil of Lavandula pubescens.
Nu. Ret time RI Compound name Area %
1 6.93 988 Myrcene 2.05
2 7.383 1002 α-Phellandrene 0.14
3 7.456 1008 3-δ-Carene 0.20
4 7.681 1014 α-Terpinene 0.15
5 7.89 1022 p-Cymene 0.20
6 8.03 1029 Limonene 0.12
7 8.104 1026 1,8-Cineole 0.05
8 8.225 1032 Ζ-β-Ocimene 2.63
9 8.519 1044 Ε-β-Ocimene 0.20
10 9.667 1086 Terpinolene 5.34
11 9.781 1089 p-Cymenene 0.10
12 10.068 1054 α-Terpinolene 0.04
13 10.439 1108 1,3,8-p-Menthatriene 0.03
14 12.631 1179 p-Cymen-8-ol 0.53
15 12.874 1186 4-Terpineol 0.21
16 13.029 1201 4,5-Epoxy-1-isopropyl-4-methyl-1-cyclohexene 0.36
17 13.308 1215 2,6-Dimethyl-3,5,7-octatriene-2-ol 0.08
18 14.158 1241 Carvacrol methyl ether 5.36
19 15.695 1286 ymol 0.26
20 16.071 1298 Carvacrol 65.27
21 16.082 1294 Para-menth-1-en-9-ol 1.73
22 19.241 1417 ε-Caryophyllene 6.21
23 20.172 1452 α-Humulene 0.20
24 21.544 1505 Β-Bisabolene 7.43
25 23.387 1582 Caryophyllene oxide 1.11
Table 2: Test microorganisms.
Microorganisms Species name Source Notes
Bacteria
Staphylococcus aureus ATCC 25923 Gram positive
Proteus vulgaris ATCC 13315 Gram negative
Pseudomonas aeruginosa ATCC 27853
Salmonella typhi ATCC 14028
Escherichia coli ATCC 25922
Klebsiella pneumonia ATCC 13883
Candida Candida albicans
CBS6589
CBS9120
BERC M77
Clinical isolates (vulvovaginal and cutaneous candidiasis patients)BERC N17
BERC N40
Dermatophytes
Microsporum canis
CBS 132.88
BERC MC03
Clinical isolates (dermatophytosis patients)BERC MC39
BERC MC13
Trichophyton rubrum
BERC CBS 392.58
BERC TR64
Clinical isolates (dermatophytosis patients)BERC TR67
BERC TR69
Trichophyton mentagrophytes
CBS 106.67
BERC TM1
Clinical isolates (dermatophytosis patients)BERC TM2
BERC TM78
Epidermophyton floccosum CBS 358.93
Evidence-Based Complementary and Alternative Medicine 3

of the treatment. Effective concentration fifty (EC
50
) that
caused 50% growth inhibition was estimated using Micro-
soft Excel 2010 under Windows 10.
Minimum inhibitory concentration (MIC) and mini-
mum fungicidal concentration (MFC) were assessed fol-
lowing the previously reported assays [29, 30].
3. Results and Discussion
3.1. GC-MS Analysis. ere are no reports on the EO
composition of L. pubescens growing wild in Palestine and
only a few such reports are available worldwide [6, 8, 13, 31].
Hydrodistillation of the L. pubescens leaves yielded 1.9 mL
per 250 g fresh plant material.
e GC-MS analysis of the EO led to the identification of
25 components (Table 1). e main identified compounds
were carvacrol (65.27%), β-bisabolene (7.43%), ε-car-
yophyllene (6.21%), carvacrol methyl ether (5.36%), terpi-
nolene (5.34%), Z-β-ocimene (2.63%), myrcene (2.05%),
para-menth-1-en-9-ol (1.73%), and caryophyllene oxide
(1.11%), representing 97.13% of the total oil. Hence, the EO
from the Palestinian L. pubescens can be characterized as
carvacrol chemotype. e oxygenated monoterpenes were
the dominant (73.26%) chemical group within the constit-
uents, followed by sesquiterpene hydrocarbons (13.84%),
monoterpene hydrocarbons (11.79%), and oxygenated ses-
quiterpenes (1.11%). e EO chemical profile in this study is
qualitatively comparable to that formerly reported from
Yemen where the EO has shown to be carvacrol chemotype
(60.9–77.5%) [6, 31].
Carvacrol is a monoterpenic phenol that is bio-
synthesized from c-terpinene [32] through p-cymene [33].
ese two compounds are therefore present in the L.
pubescens EO. Biosynthetic intermediates such as terpinene-
4-ol [34] and p-cymen-8-ol [35] are also present [36].
3.2. Antioxidant Potential. e antioxidant activity of EOs is
a biological property of great interest because the oils that
possess the ability of scavenging free radicals may play an
important role in the prevention of some diseases that may
result from oxidative stress damages caused by the free
radicals, such as brain dysfunction, Alzheimer’s disease,
obesity, cancer, heart disease, and immune system decline
[37–39]. e consumption of naturally occurring antioxi-
dants that can be used to protect human beings from oxi-
dative stress damages has therefore been increased [38]. is
work reports the antioxidant activities of L. pubescens EO as
assessed by ABTS and RP assays (Table 3).
e antioxidant potential of LP EO was generally high
with RP
50
and IC
50
of 0.16 and 0.18 μL/mL using RP and
ABTS assays, respectively. Interestingly, carvacrol has shown
comparable antioxidant activity (IC
50
�0.03 μL/mL) relative
to the potent antioxidant agent BHT using the ABTS assay
and high antioxidant capacity (RP
50
�0.07 μL/mL) compa-
rable to the tested potent antioxidant agents (Trolox and
BHT) (Table 3).
e antioxidant capacities of L. pubescens EO may be
attributed to the high content of the oil’s major phenolic
constituents, especially carvacrol, which were confirmed as
effective antioxidant compounds with potential health
benefits [40]. Our results demonstrate that the EOs of L.
pubescens and carvacrol have a significant strength to
provide electrons to reactive oxygen species (ROS), con-
verting them into more stable nonreactive species and
ending the free ROS chain reaction.
3.3. Antibacterial Activity. Results for the in vitro antibac-
terial activity of L. pubescens EO and carvacrol are presented
in Figures 1 and 2 as PI and MIC. e EO and carvacrol had
similar high antibacterial activities against all bacteria tested
with a PI range of 37.2–95.7% and MIC range of 0.2–0.7 μL/
mL. Staphylococcus aureus (Gram-positive) was the most
susceptible strain (PI value 95.7% for EO and 87% for
carvacrol). Among the tested Gram-negative bacterial
strains, the EO has comparable inhibition effect with PI
values 46.5, 49.8, 51.1, 51.3, and 49.6% against Salmonella
typhi,Proteus vulgaris,Pseudomonas aeruginosa,E.coli, and
K. pneumonia, respectively.
e strong antibacterial activity of the EO may be as-
cribed to the presence of high % of oxygenated monoter-
penes (73.26%) such as carvacrol (65.27%), which was found
to destroy cell morphology and biofilm viability in typical
biofilm construction by increasing the permeability and
reducing polarization of the cytoplasmic membrane [41–43].
e antibacterial activity of carvacrol has been mainly at-
tributed to its hydrophobicity and the free hydroxyl group in
its structure [44]. With the appropriate hydrophobicity of
carvacrol, the compound can be accumulated in the cell
membrane, while its hydrogen-bonding and its proton-re-
lease abilities may induce conformational modification of
the membrane resulting in cell death [45]. Our results can,
therefore, explain the association of the use of the LP EO in
TAPHM as an antiseptic, due to the antibacterial action of
carvacrol which has been previously confirmed [46, 47].
3.4. Anticandidal Activity. Candidiasis is a mycotic infection
caused by several species of Candida, which can endorse
superficial and systemic opportunist diseases worldwide.
e current treatment against candidiasis is based on syn-
thetic antimycotic drugs. Most presently available anti-
candidal drugs have limitations that hamper their use, which
Table 3: Antioxidant activities of essential oil from aerial parts of
Lavandula pubescens.
ABTS Reductive
potential
IC
50
(μL/mL)
Oil 0.18 ±0.05 0.16 ±0.0
Carvacrol 0.03 ±0.0 0.07 ±0.0
Standard antioxidants IC
50
(mg/ml)
Trolox 0.05 ±0.0 0.08 ±0.0
Ascorbic
acid 0.05 ±0.0 0.04 ±0.0
BHT 0.03 ±0.0 0.07 ±0.01
4Evidence-Based Complementary and Alternative Medicine

necessitates the search for safe and effective antimycotic
agents.
e results of this study showed that the EO and car-
vacrol possessed strong inhibitory activity against C. albi-
cans (isolated from cutaneous and vulvovaginal infections)
with average PI values of 103.4% for EO and 113.6% for
carvacrol (Figure 1) and MIC values of 0.47 and 0.24 μL/mL
for EO and carvacrol, respectively (Figure 2). e strong
anticandidal activity of EO can, therefore, be correlated with
its high content of carvacrol owing to the anticandidal ac-
tivity of carvacrol which has been previously confirmed [48].
3.5. Antidermatophytic Activity. Aromatic plants EOs are
known to be mycostatic or fungicidal and represent a po-
tential source of new antimycotics [49]. In view of the in-
creasing resistance to the classical antimycotics, the EOs and
their active constituents may be beneficial in the manage-
ment of mycoses, especially dermatophytosis [50]. In the
present study, the L. pubescens EO showed strong activity
against M. canis,T. rubrum, T. mentagrophytes, and
E. floccosum as indicated by their PI, MIC, MFC, and EC
50
values (Figure 3).
e EO of L. pubescens and carvacrol showed a dose-
dependent activity against the tested dermatophytes (Fig-
ure 4). Overall, as the dose of the EO or carvacrol increased,
the inhibitory activity against the tested dermatophytes
increased indicated by heightened mycelial growth inhibi-
tion. e radial mycelial growth of all tested isolates was
completely inhibited by the EO and carvacrol at 0.5, 0.25,
and 0.125 μL/mL concentration. However, at lower doses
(0.004–0.063 μL/mL), the EO was still more active on the
mycelial growth of T. mentagrophytes than other tested
dermatophytes at 0.63 μL/mL, PI �89.7% (Figure 3).
e MIC and EC
50
values of the EO of L. pubescens on
the tested dermatophytes were in the ranges of 0.08–0.16 μL/
mL and 0.05–0.06 μL/mL, respectively. However, EO
showed a fungicidal effect on the four studied dermato-
phytes and the MFCs were in the range of 0.16–0.25 μL/mL.
T. mentagrophytes were more susceptible to L. pubescens EO
than the other tested fungi with MIC, MFC, and EC
50
values
of 0.05, 0.08, and 0.16μL/mL, respectively.
e strong antifungal property could be attributed to the
major component of the EOs, carvacrol, and the oxygenated
monoterpene, which exhibited strong inhibitory activity
against the tested dermatophytes (Figure 3) with PI, MIC,
46.5 49.8 51.1 51.3
95.7
49.6
103.4
41.3 40.0 37.2 37.5
87.0
60.8
113.6
0.0
20.0
40.0
60.0
80.0
100.0
120.0
S. typhi Pro. vulgaris P. aeruginosa E. coli Staph. aureus K. pneumonia C. albicans
Percent of inhibition (%)
L.pubescens
Carvacrol
Figure 1: Antimicrobial activity (percent of inhibition) of essential oil and carvacrol on bacteria and Candida albicans.
0.2
0.5
0.3 0.3 0.3
0.5 0.5
0.2
0.7
0.4
0.7
0.4
0.2 0.2
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Minimum inhibitory
concentration (MIC) (µL/mL)
S. typhi Pro. vulgaris P. aeruginosa E. coli Staph. aureus K. pneumonia C. albicans
L.pubescens
Carvacrol
Figure 2: Minimum inhibitory concentration (MIC) values of the essential oil against bacteria strains and Candida albicans.
Evidence-Based Complementary and Alternative Medicine 5

EC
50
, and MFC values ranging from 76.7 to 100%,
0.063–0.125 μL/mL, 0.01–0.1 μL/mL, and 0.03–0.63 μL/mL,
respectively. e monoterpene alcohols are water soluble
and possess functional alcohol groups that explain their
strong antidermatophyte activity [49].
In general, EO and carvacrol can exert their anti-
dermatophyte actions due to membrane damage, cytoplasmic
content leakage, and ergosterol depletion [49, 51–53].
3.6. Enzyme Inhibitory Activities of Essential Oil
3.6.1. Anticholinesterase Activity. Cholinesterase inhibitors
(ChEIs) have recently become the most widely used drugs
for the management of Alzheimer’s disease (AD) [54]. ChEIs
play a crucial role in the memory enhancement of AD
patients through increasing ACh concentration in neural
synaptic clefts and thus improving the brain cholinergic
transmission and decreasing β-amyloid aggregation and
neurotoxic fibrils formation [55–57]. However, synthetic
AChEIs including galanthamine and tacrine have restric-
tions owing to the short half-life and adverse side effects such
as digestive disorders, nausea, and dizziness [58, 59]. Hence,
it is necessary to explore new safe alternatives with superior
characteristics to deal with AD.
Several plants and phytochemical compounds have
revealed cholinesterase inhibitory capacity and therefore can
be valuable in the management of neurological disturbances
[21]. In this study, LP EO was investigated for its in vitro
cholinesterases (AChE and BuChE) inhibitory activities. e
EO and carvacrol have shown to possess high AChE
(IC
50
�0.9, and 1.43 μL/mL, respectively) and medium
BuChE (IC
50
6.82, and 7.75 μL/mL, respectively) inhibitory
activities (Table 4).
us, the high AChE inhibitory effect of the L. pubescens
EO in the current study may be mainly associated with its
major component, carvacrol, and with its high phenol
content. Overall, the tested EO was shown to be more se-
lective inhibitors for acetylcholinesterase than butyr-
ylcholinesterase with a selectivity index (SI) of 7.58.
Our results demonstrate that LP EO could be a valued
natural source of AChEIs, e.g., carvacrol, with effective
inhibitory activities against the principal enzymes associated
with AD and could signify a basis for developing a new
treatment strategy for Alzheimer’s using plant-derived
AChEIs.
3.6.2. Pancreatic Lipase Inhibitory Activity. Pancreatic li-
pase, the principal enzyme associated with obesity, plays a
key role in the efficient digestion of acylglycerols [60]. e
hydrolysis of glycerides to glycerol and free fatty acids is
performed by lipases. Taking into consideration that 50–70%
of the total dietary fat hydrolysis is performed by pancreatic
lipase, enzyme inhibition is one of the approaches used to
treat obesity [60]. e mechanism involves inhibition of
43.22
66.53
89.96
58.78
0.16 0.13 0.08 0.13
0.22
0.25
0.16
0.25
0.06 0.06 0.05 0.06
0
10
20
30
40
50
60
70
80
90
100
M. canis T. rubrum T. mentagrophytes E. floccosum 0.0
0.1
0.2
0.3
0.4
0.5
Percentage (%)
Concentration (µL/mL)
MFC
EC50
PI
MIC
(a)
Percentage (%)
94.9 100.0 100.0
76.7
0.06 0.06 0.06
0.13
0.06 0.06
0.03
0.06
0.03 0.01
0.04
0.01
0
10
20
30
40
50
60
70
80
90
100
M. canis T. rubrum T. mentagrophytes E. floccosum 0.0
0.1
0.2
0.3
0.4
0.5
Concentration (µL/mL)
MFC
EC50
PI
MIC
(b)
Figure 3: Percentage of mycelial growth inhibition (PI) with MIC, MFC, and EC
50
values of (a) of Lavandula pubescens EO and (b) carvacrol
against the tested dermatophytes.
0
20
40
60
80
100
120
0.0 0.1 0.2 0.3 0.4 0.5 0.6
Mycelial growth inhibition (%)
Concentration (µL/mL)
M. canis
T. r ubru m
T. m ent agrophy te s
E. floccosum
(a)
Mycelial growth inhibition (%)
Concentration (µL/mL)
M. canis
T. r ubru m
T. m ent agrophy te s
E. floccosum
0
20
40
60
80
100
120
0.0 0.1 0.2 0.3 0.4 0.5 0.6
(b)
Figure 4: Mycelial growth inhibition activity of (a) Lavandula pubescens essential oil and (b) carvacrol against the tested dermatophytes.
6Evidence-Based Complementary and Alternative Medicine

dietary triglyceride absorption, as this is the main source of
excess calories [61]. Besides, pancreatic lipase inhibition does
not alter any central mechanism, which makes it an ideal
approach for obesity treatment [62]. e pancreatic lipase has
been widely used for the determination of the potential ef-
ficacy of natural products as antiobesity agents [62].
In the present study, L. pubescens EO and carvacrol were
assessed for their activity against pancreatic lipase. e EO
exhibited high inhibitory activity against PPL with IC
50
of
1.08 μL/mL (Table 5). e high antiobesity activity of L.
pubescens EO may be mainly ascribed to its high content of
carvacrol which has been reported to inhibit visceral adi-
pogenesis and adipocyte differentiation in animal cells and
decrease body weight and plasma lipid levels [63, 64].
However, carvacrol on its own cannot explain the high
activity of EO, and therefore the totality of constituents of
the EO may act synergistically to exert such high antiobesity
activity. e higher pancreatic lipase inhibitory effects of L.
pubescens EO may, therefore, be attributed to its high
content of bioactive phenolic acids and flavonoids acting
together in a synergistic style [22].
e current study has indicated the ability of the EO to
exercise health benefit attributes by inhibiting the pancreatic
lipase enzyme (responsible for digestion and absorption of
triglycerides) and thus lead to the reduction of fat absorption.
4. Conclusions
e main constituent of L. pubescens EO was determined as
carvacrol in wild plants. e results demonstrate that the plant
is a valuable natural source for carvacrol-rich EO with
promising potential antimicrobial, antiobesity, and anti-AD
health effects (Figure 5). Our results support the use of
L. pubescens EO as a natural complementary treatment in
TAPHM. is is the first report on the antidermatophytic,
AChE inhibitory, and antiobesity effects of L. pubescens EO. In
conclusion, our results might be useful for further investigation
aiming at clinical applications of L. pubescens EO and carvacrol
in the management of AD, obesity, and microbial skin in-
fections including dermatophytosis, candidiasis, and others.
Abbreviations
ABTS: 2,2′-Azino-bis (3-ethylbenzo thiazoline-6-sulphonic
acid)
AChE: Acetylcholinesterase
AD: Alzheimer’s disease
AI: Activity index
BERC: Biodiversity and environmental research center
BuChE: Butyrylcholinesterase
CLSI: Clinical and Laboratory Standards Institute
EC
50
: Effective concentration fifty
EO: Essential oil
GC-MS: Gas chromatography-mass spectrometry
IC
50
: Inhibitory concentration fifty
MFC: Minimum fungicidal concentration
MIC: Minimum inhibitory concentration
PI: Percent of inhibition
PPL: Porcine pancreatic lipase
ROS: Reactive oxygen species
RP: Reductive potential
TAPHM: Traditional Arabic Palestinian herbal medicine.
Data Availability
e data used to support the findings of this study are
available from the corresponding author upon request.
Conflicts of Interest
e authors declare no conflicts of interest.
Table 4: Cholinesterase inhibitory activity (ChEIA) of L. pubescens essential oil.
IC
50
(μL/mL) Selectivity index (SI)∗
Acetylcholinestrase Buterylcholinestrase
Oil 0.9 ±0.14 6.82 ±0.35 7.58±0.13
Carvacrol 1.43 ±0.56 7.75 ±0.25 5.42 ±0. 01
Neostagmin (μg/mL) 1.54 ±0.00 174.41 ±0.00 113.18 ±0.00
∗SI �IC
50
BuChE/IC
50
AChE.
Table 5: Antiobesity activities of Lavandula pubescens essential oil.
IC
50
(μL/mL)
Oil 1.08 ±0.35
Carvacrol 6.63 ±1.03
Orlistat (μg/ml) 0. 12 ±0.03
Carvacrol-rich essential
oil Antibacterial
Anticandidal
AntidermatophyticAnticholinestrase
Antipancreatic
lipase
Antioxidant
Figure 5: Beneficial health effects of Lavandula pubecsens essential
oil and its main active constituent, carvacrol.
Evidence-Based Complementary and Alternative Medicine 7

Acknowledgments
is research was partially funded by the Middle East Re-
gional Cooperation (MERC) project M36-010 (award
number: SIS700 15G360 10).
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