I
n
t
e
r
n
at
io
n
al
Jou
r
n
al
of
A
d
van
c
e
s
i
n
A
p
p
li
e
d
S
c
ie
n
c
e
s
(
I
JA
A
S
)
V
ol
.
14
, N
o.
4
,
D
e
c
e
m
be
r
20
25
, pp.
1061
~
1071
I
S
S
N
:
2252
-
8814
,
D
O
I
:
10.11591/
ij
a
a
s
.
v14.
i
4
.
pp1061
-
1071
1061
Jou
r
n
al
h
om
e
page
:
ht
tp
:
//
ij
aas
.i
ae
s
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A
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O
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M
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iy
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o
1
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it
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m
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it
i
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s
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1
S
t
udy P
r
ogr
a
m
of
A
g
r
i
c
ul
t
ur
a
l
P
r
oduc
t
T
e
c
hnol
ogy
, F
a
c
ul
t
y of
A
gr
i
c
ul
t
u
r
a
l
T
e
c
hnol
ogy, J
e
m
be
r
U
ni
ve
r
s
i
t
y, J
e
m
be
r
, I
ndone
s
i
a
2
C
e
nt
e
r
of
B
i
ot
e
c
hnol
ogy, N
a
t
i
ona
l
R
e
s
e
a
r
c
h A
ge
nc
y,
B
ogor
, I
ndone
s
i
a
3
D
e
pa
r
t
m
e
nt
of
A
gr
i
c
ul
t
ur
e
, F
a
c
ul
t
y of
A
ni
m
a
l
a
nd A
gr
i
c
ul
t
u
r
a
l
S
c
i
e
nc
e
s
, D
i
pone
gor
o U
ni
ve
r
s
i
t
y, S
e
m
a
r
a
ng, I
ndone
s
i
a
A
r
t
ic
le
I
n
f
o
A
B
S
T
R
A
C
T
A
r
ti
c
le
h
is
to
r
y
:
R
e
c
e
iv
e
d
N
ov
18
,
2024
R
e
vi
s
e
d
J
ul
5
,
2025
A
c
c
e
pt
e
d
J
ul
14
,
2025
The
basil
plant
belongs
to
the
Lamiaceae
family
and
contains
various
active
compound
s,
includi
ng
phenols,
saponin
s,
alkaloid
s,
flavonoi
ds,
tanni
ns,
and
essential
oils.
These
compound
s
have
antimi
crobial
activit
y
against
Streptococcus
mutans
and
Candida
albicans
,
two
types
of
bacteria
t
hat
can
cause
bad
breath.
The
addition
of
basil
essential
oil
to
hard
candy
has
the
potential
to
reduce
bad
breath.
This
study
aimed
to
determi
ne
the
concentrati
on
effect
of
basil
essential
oil
on
hard
candy
in
inhibi
ting
the
growth
of
Streptococcus
mutans
and
Candi
da
albicans
and
its
accepta
nce
by
the
panelists.
This
research
was
conducted
with
five
treatment
s
with
variations
in
the
concentration
of
basil
essential
oil,
which
were
0,
0.2
5,
0.5,
0.75,
and
1%.
The
results
showed
that
the
higher
basil
essent
ial
oil
concentrati
on
in
hard
candy
inhibi
ted
the
growth
of
Streptococcus
mutans
and
Candida
albicans
.
The
best
treatment
was
at
0.75%
basil
essent
ial
oil,
with
sensory
panelist
acceptance
for
color
69%,
aroma
57%,
taste
43
%,
and
overall
58%.
Several
compounds
in
bas
il
essential
oil,
including
li
nalool,
eugenol,
caryophyll
ene,
and
trans
-
α
-
bergamotene,
are
thought
to
con
tribute
to the ability o
f this cand
y to inhibit micr
obial growth.
K
e
y
w
o
r
d
s
:
B
a
s
il
C
andi
da albi
c
ans
E
s
s
e
nt
ia
l
oi
l
H
a
r
d c
a
ndy
St
r
e
pt
oc
oc
c
u
s
m
ut
ans
This is an
open
acce
ss artic
le unde
r the
CC BY
-
SA
license.
C
or
r
e
s
pon
di
n
g A
u
th
or
:
S
it
i
S
us
a
nt
i
D
e
pa
r
tm
e
nt
of
A
gr
ic
ul
tu
r
e
, F
a
c
ul
ty
of
A
ni
m
a
l
a
nd A
gr
ic
ul
tu
r
a
l
S
c
ie
nc
e
s
, D
ip
one
gor
o U
ni
ve
r
s
it
y
P
r
of
. S
oe
da
r
to
S
t.
, T
e
m
ba
la
ng
, S
e
m
a
r
a
ng, C
e
nt
r
a
l
J
a
va
50275,
I
ndone
s
ia
E
m
a
il
:
s
it
is
us
a
nt
i@li
ve
.undip.a
c
.i
d
1.
I
N
T
R
O
D
U
C
T
I
O
N
H
a
li
to
s
is
ha
s
b
e
c
om
e
a
c
om
m
on
is
s
ue
f
or
m
a
ny
in
di
vi
dua
ls
.
I
t
ha
s
be
e
n
r
e
por
te
d
th
a
t
80
-
90%
of
ha
li
to
s
is
or
ig
in
a
te
s
f
r
om
th
e
or
a
l
c
a
vi
ty
[
1]
.
C
a
u
s
e
s
w
it
hi
n
th
e
or
a
l
c
a
vi
ty
a
r
e
ty
pi
c
a
ll
y
a
s
s
o
c
ia
te
d
w
it
h
poor
or
a
l
hygi
e
ne
,
de
nt
a
l
c
a
r
ie
s
,
a
nd
or
a
l
in
f
e
c
ti
ons
[
2]
.
T
he
pr
e
s
e
nc
e
of
c
e
r
ta
in
m
ic
r
obi
a
l
s
pe
c
ie
s
a
ls
o
c
ont
r
ib
ut
e
s
to
de
nt
a
l
c
a
r
ie
s
,
m
out
h
ul
c
e
r
s
,
a
nd
c
a
ndi
di
a
s
i
s
,
w
hi
c
h
a
r
e
a
m
ong
th
e
pr
im
a
r
y
c
a
us
e
s
of
h
a
li
to
s
is
.
T
he
s
e
m
ic
r
obe
s
i
nc
lu
de
St
r
e
pt
oc
o
c
c
us
m
ut
an
s
a
nd
C
andi
da
s
pe
c
ie
s
[
3]
, [
4]
.
B
a
s
il
(
O
c
imum
ba
s
il
ic
um
L.
)
is
a
pl
a
nt
th
a
t
gr
ow
s
a
bunda
nt
ly
i
n
I
ndone
s
ia
. T
hi
s
pl
a
nt
h
a
s
lo
ng
be
e
n
us
e
d
in
tr
a
di
ti
ona
l
I
ndone
s
ia
n
c
ui
s
in
e
.
M
or
e
ove
r
,
ba
s
il
ha
s
be
e
n
r
e
por
te
d
to
a
ll
e
vi
a
te
ba
d
br
e
a
th
,
body
odor
,
a
nd
va
r
io
us
a
il
m
e
nt
s
s
uc
h
a
s
f
e
ve
r
,
di
a
r
r
he
a
,
bl
oa
ti
ng
or
in
di
ge
s
ti
on,
la
c
ta
ti
on
pr
obl
e
m
s
,
r
he
um
a
ti
s
m
,
m
out
h
ul
c
e
r
s
,
a
nd
ot
he
r
he
a
lt
h
be
ne
f
it
s
[
5]
.
T
he
pr
im
a
r
y
c
om
pone
nt
s
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
in
c
lu
de
c
it
r
a
l
(
33.92%
)
w
it
h
c
is
-
c
it
r
a
l
(
14.86%
)
a
nd
t
r
a
ns
-
c
it
r
a
l
(
18.96%
)
a
s
it
s
m
a
jo
r
c
ons
ti
tu
e
nt
s
[
6]
.
C
it
r
a
l
is
a
m
onot
e
r
pe
noi
d
c
om
pound
[
7]
th
a
t
pos
s
e
s
s
e
s
a
nt
im
ic
r
obi
a
l
[
8]
,
f
la
vor
in
g,
a
nd
p
r
e
s
e
r
va
ti
ve
pr
ope
r
ti
e
s
,
a
nd
a
ls
o
pl
a
ys
a
r
ol
e
in
th
e
s
ynt
he
s
is
of
vi
ta
m
in
A
.
B
a
s
il
e
s
s
e
nt
ia
l
oi
l
e
xhi
bi
ts
a
nt
im
i
c
r
obi
a
l
a
c
ti
vi
ty
a
ga
in
s
t
St
r
e
pt
oc
o
c
c
us
m
ut
an
s
,
L
ac
to
bac
il
lu
s
c
as
e
i
,
a
nd
C
andi
da
al
bi
c
an
s
a
t
m
in
im
um
in
hi
bi
to
r
y
c
onc
e
nt
r
a
ti
on
(
M
I
C
)
va
lu
e
s
of
0.08,
0.3,
a
nd
0.08%
(
v/
v)
,
r
e
s
pe
c
ti
ve
ly
[
9]
.
B
a
s
il
e
s
s
e
nt
ia
l
oi
l
e
xhi
bi
t
s
a
nt
ib
a
c
te
r
ia
l
a
c
ti
vi
ty
a
ga
in
s
t
St
aphy
lo
c
oc
c
u
s
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
S
N
:
2252
-
8814
I
nt
J
A
dv A
ppl
S
c
i
,
V
ol
.
14
, N
o.
4
,
D
e
c
e
m
be
r
20
25
:
1061
-
1071
1062
aur
e
us
a
nd
E
s
c
h
e
r
ic
hi
a c
ol
i
[
10]
, w
it
h M
I
C
s
of
0.5 a
nd 0.25%
(
v/
v)
, r
e
s
pe
c
ti
ve
ly
. I
ts
a
nt
im
ic
r
obi
a
l
pr
ope
r
t
ie
s
in
di
c
a
te
pot
e
nt
ia
l
f
or
de
ve
lo
pm
e
nt
i
n ha
r
d c
a
ndy pr
oc
e
s
s
in
g.
H
a
r
d
c
a
ndy
i
s
a
non
-
c
r
y
s
t
a
ll
in
e
c
onf
e
c
ti
on
e
r
y
pr
odu
c
t
w
it
h
a
h
a
r
d
te
xt
ur
e
[
11]
m
a
de
f
r
om
a
m
ix
tu
r
e
of
s
u
c
r
o
s
e
,
gl
u
c
o
s
e
,
w
a
te
r
,
a
nd
a
ddi
ti
on
a
l
in
gr
e
d
ie
nt
s
s
u
c
h a
s
f
la
vor
in
gs
, c
ol
or
a
nt
s
,
a
nd a
c
i
di
f
ie
r
s
. T
h
e
pr
im
a
r
y
in
gr
e
di
e
nt
s
in
h
a
r
d
c
a
n
dy
pr
odu
c
ti
on
a
r
e
s
uc
r
os
e
,
w
a
t
e
r
,
a
nd
gl
uc
o
s
e
s
yr
up
or
i
nve
r
t
e
d
s
ug
a
r
.
O
th
e
r
c
om
pon
e
nt
s
i
nc
lu
d
e
f
l
a
vor
in
gs
,
c
ol
or
a
n
ts
,
a
nd
a
c
i
di
f
ie
r
s
.
T
h
e
a
ddi
ti
on
of
e
s
s
e
nt
ia
l
oi
l
s
to
h
a
r
d
c
a
ndy
c
a
n
pr
ovi
de
f
la
vor
w
hi
l
e
s
e
r
vi
n
g
a
s
a
s
our
c
e
of
a
c
ti
ve
c
om
p
ound
s
b
e
ne
f
i
c
ia
l
f
or
or
a
l
he
a
lt
h.
E
s
s
e
nt
i
a
l
o
il
s
po
s
s
e
s
s
a
nt
im
ic
r
obi
a
l
pr
o
pe
r
ti
e
s
a
nd
ha
ve
be
e
n
a
ppl
ie
d
to
va
r
io
u
s
ty
p
e
s
of
f
ood
pr
oduc
t
s
,
in
c
lu
di
n
g
ba
s
il
e
s
s
e
nt
i
a
l
oi
l
(
O
c
imu
m
s
anc
t
um
L
.)
a
s
a
n
a
nt
im
i
c
r
obi
a
l
a
g
e
nt
i
n
s
of
t
c
a
ndy
[
12]
,
A
r
om
a
ti
c
gi
ng
e
r
(
K
a
e
m
pf
e
r
i
a
gal
a
nga
L.
)
in
ha
r
d
c
a
ndy
[
13]
,
a
nd
T
r
i
gona
hon
e
y
(
T
r
ig
o
na
it
am
a
)
a
s
w
e
ll
a
s
m
i
c
r
oe
nc
a
ps
ul
a
t
e
d
p
a
tc
houl
i
oi
l
(
P
ogos
te
m
on
c
a
bl
in
B
e
nt
h.)
-
b
a
s
e
d
e
s
s
e
nt
i
a
l
oi
l
s
in
ha
r
d
c
a
nd
y
[
14]
.
R
e
s
e
a
r
c
h
on
ba
s
il
-
in
f
u
s
e
d
ha
r
d
c
a
ndy
r
e
m
a
in
s
li
m
it
e
d,
pa
r
ti
c
ul
a
r
l
y
c
o
nc
e
r
ni
ng
i
ts
a
c
ti
vi
ty
a
ga
i
ns
t
or
a
l
pa
t
hog
e
ns
r
e
s
pon
s
ib
l
e
f
or
d
e
nt
a
l
c
a
r
ie
s
a
nd
ha
li
to
s
is
.
T
h
e
r
e
f
or
e
,
th
i
s
s
t
udy
i
s
c
r
uc
i
a
l
to
d
e
ve
l
op
a
n
o
pt
im
a
l
ba
s
il
ha
r
d
c
a
ndy
w
it
h
a
n
ti
m
ic
r
o
bi
a
l
pr
o
pe
r
ti
e
s
a
ga
in
s
t
p
a
th
og
e
ni
c
m
ic
r
ob
e
s
. T
he
a
im
of
t
hi
s
r
e
s
e
a
r
c
h w
a
s
t
o de
te
r
m
in
e
t
h
e
e
f
f
e
c
t
of
e
s
s
e
nt
ia
l
oi
l
c
on
c
e
nt
r
a
ti
on
on a
nt
i
m
ic
r
obi
a
l
a
c
ti
vi
ty
a
nd c
on
s
um
e
r
a
c
c
e
pt
a
nc
e
,
a
s
w
e
l
l
a
s
t
o
i
de
nt
if
y
t
he
m
os
t
e
f
f
e
c
ti
v
e
t
r
e
a
tm
e
nt
.
2.
R
E
S
E
A
R
C
H
M
E
T
H
O
D
2.1.
E
s
s
e
n
t
ia
l
oi
l
d
is
t
il
la
t
io
n
T
he
e
xt
r
a
c
ti
on
of
e
s
s
e
nt
ia
l
oi
l
w
a
s
c
a
r
r
ie
d
out
us
in
g
t
he
s
te
a
m
di
s
ti
ll
a
ti
on
m
e
th
od
[
15
]
.
T
hr
e
e
ki
lo
gr
a
m
s
of
w
il
te
d
dr
ie
d
b
a
s
il
w
e
r
e
pl
a
c
e
d
in
a
di
s
ti
ll
a
ti
on
a
ppa
r
a
tu
s
w
it
h
a
w
a
te
r
-
to
-
m
a
te
r
ia
l
r
a
ti
o
of
1:
2.
S
te
a
m
di
s
ti
ll
a
ti
on
w
a
s
p
e
r
f
or
m
e
d
a
t
a
tm
os
ph
e
r
ic
pr
e
s
s
ur
e
f
or
8
hour
s
.
T
he
r
e
s
ul
ti
ng
s
te
a
m
w
a
s
c
onde
ns
e
d
to
obt
a
in
th
e
di
s
ti
ll
a
te
,
w
hi
c
h
w
a
s
c
ol
le
c
te
d
in
a
s
e
p
a
r
a
ti
ng
f
unne
l.
T
he
di
s
ti
ll
a
te
w
a
s
le
f
t
to
s
ta
nd
f
or
24 hour
s
unt
il
t
w
o l
a
ye
r
s
f
or
m
e
d, w
hi
c
h w
e
r
e
t
he
n s
e
pa
r
a
te
d.
2.2.
H
ar
d
c
an
d
y p
r
e
p
ar
at
io
n
H
a
r
d
c
a
ndy
w
a
s
pr
e
pa
r
e
d
us
in
g
th
e
m
e
th
od
de
s
c
r
ib
e
d
in
[
16]
.
W
hi
te
gr
a
nul
a
te
d
s
uga
r
(
120
g)
w
a
s
m
ix
e
d
w
it
h
20
m
l
of
w
a
te
r
a
nd
he
a
te
d
a
t
100
°
C
.
A
dd
60
gr
a
m
s
of
gl
uc
os
e
,
a
nd
th
e
m
ix
tu
r
e
w
a
s
f
ur
th
e
r
he
a
te
d
unt
il
th
e
f
in
a
l
h
a
r
d
-
c
r
a
c
k
te
m
pe
r
a
tu
r
e
of
150
°C
w
a
s
r
e
a
c
he
d
,
th
e
n
a
ll
ow
e
d
to
c
ool
a
t
60
°C
.
B
a
s
il
e
s
s
e
nt
ia
l
oi
l
w
a
s
a
dde
d
a
c
c
or
di
ng
to
(
0,
0.25,
0.5,
0.75,
a
nd
1%
)
,
pour
e
d
in
to
m
ol
ds
,
a
nd
le
f
t
to
ha
r
de
n
a
t
r
oom
te
m
pe
r
a
tu
r
e
.
H
a
r
d
c
a
ndy
w
a
s
th
e
n
r
e
m
ove
d
f
r
om
th
e
m
ol
ds
a
nd
s
to
r
e
d
in
s
e
a
le
d
gl
a
s
s
c
ont
a
in
e
r
s
f
or
s
ubs
e
que
nt
t
e
s
ti
ng.
2.3. B
ac
t
e
r
ia
l
s
u
s
p
e
n
s
io
n
A
s
in
gl
e
lo
op
of
e
a
c
h
te
s
t
ba
c
te
r
iu
m
w
a
s
s
u
s
pe
nde
d
in
10
m
l
of
s
te
r
il
e
phys
io
lo
gi
c
a
l
s
ol
ut
io
n
a
nd
hom
oge
ni
z
e
d
us
in
g
a
vor
te
x
m
ix
e
r
.
T
he
a
bs
or
ba
nc
e
w
a
s
m
e
a
s
ur
e
d
a
t
a
w
a
v
e
le
ngt
h
of
625
nm
,
a
nd
th
e
tu
r
bi
di
ty
s
us
pe
ns
io
n
w
a
s
a
dj
us
te
d
to
m
a
tc
h
th
e
M
c
F
a
r
la
nd s
ta
n
da
r
d.
O
ne
m
il
li
li
te
r
of
th
e
b
a
c
te
r
ia
l
s
u
s
pe
n
s
io
n
w
a
s
tr
a
ns
f
e
r
r
e
d
in
to
a
t
e
s
t
tu
be
c
ont
a
in
in
g
9
m
l
of
s
t
e
r
il
e
di
s
ti
ll
e
d
w
a
te
r
,
f
ol
lo
w
e
d
by
s
e
r
ia
l
di
lu
ti
ons
up
to
10⁻
⁶.
T
h
e
te
s
t
s
ol
ut
io
n
w
a
s
pr
e
pa
r
e
d
by
di
s
s
ol
vi
ng
3
g
of
h
a
r
d
c
a
ndy
in
6
m
l
of
10%
di
m
e
th
yl
s
ul
f
oxi
de
(
D
M
S
O
)
s
ol
ut
io
n, w
hi
c
h ha
d be
e
n s
te
r
il
iz
e
d u
s
in
g a
n a
ut
oc
la
v
e
(
121
°C
, 2 a
tm
f
or
15 mi
nut
e
s
)
.
2.4.
I
n
h
ib
it
io
n
z
on
e
ac
t
iv
i
t
y t
e
s
t
I
nhi
bi
ti
on
z
one
a
c
ti
vi
ty
te
s
t
w
a
s
us
in
g
th
e
a
ga
r
di
f
f
us
io
n
m
e
th
od
w
it
h
s
te
r
il
e
pa
pe
r
di
s
c
s
(
K
ir
by
-
B
a
ue
r
m
e
th
od)
,
a
nd
obs
e
r
ve
d
ba
s
e
d
on
c
le
a
r
z
one
s
f
or
m
e
d
[
17]
.
S
te
r
il
e
pa
pe
r
di
s
c
s
(
6
m
m
i
n
di
a
m
e
te
r
)
w
e
r
e
s
o
a
ke
d
in
th
e
te
s
t
s
ol
ut
io
n
f
or
25
m
in
ut
e
s
.
A
to
t
a
l
of
3.4
g
of
S
a
bour
a
ud
D
e
xt
r
os
e
a
g
a
r
(
S
D
A
)
m
e
di
um
w
a
s
di
s
s
ol
ve
d
in
100
m
l
of
di
s
ti
ll
e
d
w
a
te
r
,
he
a
te
d
unt
il
c
om
pl
e
te
ly
di
s
s
ol
ve
d,
a
nd
s
te
r
il
iz
e
d
in
a
n
a
ut
oc
la
ve
a
t
121
°C
f
or
15 mi
nu
te
s
. T
he
n, 12 ml
of
s
te
r
il
e
S
D
A
m
e
di
um
w
a
s
pour
e
d i
nt
o
a
s
te
r
il
e
10
c
m
pe
tr
i
di
s
h.
O
nc
e
th
e
m
e
di
um
w
a
s
e
ve
nl
y
s
pr
e
a
d
a
nd
s
ol
id
if
ie
d,
0.1
m
l
of
ba
c
te
r
ia
l
s
u
s
pe
ns
io
n
w
a
s
in
oc
ul
a
te
d
ont
o
th
e
pe
tr
i
di
s
h a
nd e
ve
nl
y s
pr
e
a
d u
s
in
g a
D
r
ig
a
ls
ky
s
pa
tu
la
.
T
he
s
oa
ke
d
p
a
pe
r
di
s
c
s
w
e
r
e
th
e
n
pl
a
c
e
d
on
th
e
s
ur
f
a
c
e
of
th
e
te
s
t
m
e
di
um
,
f
ol
lo
w
e
d
by
in
c
uba
ti
on
a
t
37
°C
f
or
24
hour
s
.
T
he
in
hi
bi
ti
on
z
on
e
s
w
e
r
e
de
te
r
m
in
e
d
by
m
e
a
s
ur
in
g
th
e
di
a
m
e
t
e
r
of
th
e
c
le
a
r
z
one
s
f
or
m
e
d
a
r
ound
th
e
di
s
c
s
.
T
he
in
hi
bi
ti
on
z
one
di
a
m
e
te
r
s
w
e
r
e
c
a
te
gor
iz
e
d
in
to
f
our
le
ve
ls
ba
s
e
d
on
a
c
ti
vi
ty
:
w
e
a
k (
<
5 m
m
)
, m
ode
r
a
te
(
5
-
10 mm
)
, s
tr
ong (
10
-
20
m
m
)
, a
nd v
e
r
y s
tr
ong (
>
20 mm
)
.
2.5.
A
n
t
im
ic
r
ob
ia
l
t
e
s
t
in
g
T
he
a
ga
r
di
lu
ti
on
m
e
th
od
w
a
s
e
m
pl
oye
d
to
de
te
r
m
in
e
t
he
M
I
C
a
nd
I
C
50
va
lu
e
s
a
ga
in
s
t
St
r
e
pt
oc
oc
c
u
s
m
ut
ans
a
nd
C
andi
da
al
bi
c
ans
,
f
ol
lo
w
in
g
th
e
pr
oc
e
dur
e
de
s
c
r
ib
e
d
by
[
18]
.
T
he
m
e
th
od
w
a
s
c
onduc
te
d us
in
g
th
e
pour
-
pl
a
te
t
e
c
hni
que
;
1 m
l
of
ba
c
te
r
ia
l
s
us
pe
ns
io
n w
a
s
i
noc
ul
a
t
e
d i
nt
o a
s
te
r
il
e
pe
tr
i
di
s
h.
A
f
te
r
e
ve
nl
y s
pr
e
a
di
ng t
he
s
us
pe
n
s
io
n, 1 ml
of
t
he
t
e
s
t
s
ol
ut
io
n w
a
s
a
dde
d t
o t
he
di
s
h. S
ubs
e
qu
e
nt
ly
, 12 ml
of
Evaluation Warning : The document was created with Spire.PDF for Python.
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nt
J
A
dv A
ppl
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i
I
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A
nt
imi
c
r
obi
al
ac
ti
v
it
y
of
har
d c
andy
w
it
h bas
il
(
O
c
imum
s
ant
c
t
um
L
.)
e
s
s
e
nt
ia
l
oi
l
addi
ti
on
(
M
ar
ia
B
e
lg
is
)
1063
s
te
r
il
e
M
ue
ll
e
r
-
H
in
to
n
a
g
a
r
(
M
H
A
)
m
e
di
um
w
a
s
pour
e
d
in
to
th
e
pe
tr
i
di
s
h,
s
pr
e
a
d
e
ve
nl
y,
a
nd
a
ll
ow
e
d
to
s
ol
id
if
y.
T
he
pl
a
te
s
w
e
r
e
in
c
uba
t
e
d
a
t
37
°C
f
or
24
hour
s
.
A
f
te
r
in
c
uba
ti
on,
th
e
num
be
r
of
c
ol
oni
e
s
on
th
e
pe
tr
i
di
s
he
s
w
a
s
c
ount
e
d
u
s
in
g
a
c
ol
ony
c
ount
e
r
(
S
tu
a
r
t
S
c
ie
nt
i
f
ic
)
.
T
he
M
I
C
va
lu
e
w
a
s
de
te
r
m
in
e
d
ba
s
e
d
on
th
e
a
ve
r
a
ge
m
ic
r
obi
a
l
gr
ow
th
a
t
24 a
nd 48 hour
s
. T
he
r
e
s
ul
ts
w
e
r
e
us
e
d t
o c
a
lc
ul
a
t
e
t
he
M
I
C
by a
v
e
r
a
gi
ng t
he
num
be
r
of
c
ol
oni
e
s
obs
e
r
ve
d a
t
th
e
10
⁻
⁵ di
lu
ti
on l
e
ve
l
(
e
xpr
e
s
s
e
d i
n C
F
U
/m
L
)
.
2.6.
P
r
e
f
e
r
e
n
c
e
t
e
s
t
T
he
s
e
n
s
or
y
pr
e
f
e
r
e
nc
e
a
s
s
e
s
s
m
e
nt
ut
il
iz
e
d
a
h
e
doni
c
s
c
a
le
to
e
va
lu
a
te
pa
ne
li
s
t
s
'
a
c
c
e
pt
a
nc
e
of
th
e
c
ol
or
,
a
r
om
a
,
ta
s
te
,
a
nd
ove
r
a
ll
c
ha
r
a
c
te
r
is
ti
c
s
of
th
e
h
a
r
d
c
a
ndy
[
19]
.
T
he
te
s
t
in
vol
ve
d
100
unt
r
a
in
e
d
pa
ne
li
s
ts
,
bot
h
m
a
le
a
nd
f
e
m
a
le
,
a
ge
d
19
-
25
ye
a
r
s
.
T
he
e
v
a
lu
a
ti
on
s
c
a
le
w
a
s
ba
s
e
d
on
th
e
de
gr
e
e
of
li
ki
ng,
us
in
g
s
e
ve
n
c
a
te
gor
ie
s
:
1=
s
tr
ongl
y
di
s
li
ke
,
2=
di
s
li
ke
s
li
ght
ly
,
3=
di
s
li
ke
,
4=
ne
ut
r
a
l,
5=
li
ke
s
li
ght
ly
,
6=
li
ke
,
a
nd 7=
s
tr
ongl
y l
ik
e.
2.7.
E
f
f
e
c
t
iv
e
n
e
s
s
t
e
s
t
in
g
T
he
be
s
t
tr
e
a
tm
e
nt
w
a
s
de
te
r
m
in
e
d
us
in
g
th
e
e
f
f
e
c
ti
ve
ne
s
s
i
nde
x
m
e
th
od
[
20]
.
P
a
r
a
m
e
te
r
s
w
e
r
e
c
a
te
gor
iz
e
d
in
to
qua
li
ta
ti
ve
(
or
ga
nol
e
pt
ic
)
a
nd
qua
nt
it
a
ti
ve
(
p
hys
ic
a
l,
c
he
m
ic
a
l,
a
nd
a
nt
im
ic
r
obi
a
l)
gr
oups
.
E
a
c
h
pa
r
a
m
e
te
r
w
a
s
a
s
s
ig
ne
d
a
w
e
ig
ht
e
d
va
lu
e
(
B
V
)
ba
s
e
d
on
it
s
r
e
la
ti
ve
im
por
ta
nc
e
in
in
f
lu
e
nc
in
g
r
e
s
e
a
r
c
h
out
c
om
e
s
or
c
ons
um
e
r
a
c
c
e
pt
a
nc
e
,
w
it
h
w
e
ig
ht
s
r
a
ngi
ng
f
r
om
0
to
1.
T
he
w
e
ig
ht
e
d
va
lu
e
w
a
s
c
a
lc
ul
a
te
d
by
di
vi
di
ng t
he
s
c
or
e
of
e
a
c
h t
r
e
a
tm
e
nt
by t
he
t
ot
a
l
w
e
ig
ht
.
T
he
e
f
f
e
c
ti
ve
ne
s
s
s
c
or
e
w
a
s
c
a
lc
ul
a
te
d us
in
g
(
1)
.
=
−
−
(
1)
3.
R
E
S
U
L
T
S
A
N
D
D
I
S
C
U
S
S
I
O
N
3.1. I
n
h
i
b
it
io
n
z
on
e
ac
t
iv
i
t
y
T
he
in
hi
bi
ti
on
z
one
a
c
ti
vi
ty
of
ha
r
d
c
a
ndy
w
a
s
de
te
r
m
in
e
d
by
obs
e
r
vi
ng
th
e
di
a
m
e
te
r
of
th
e
c
le
a
r
z
one
a
r
ound
th
e
di
s
c
s
,
in
di
c
a
ti
ng
th
e
pr
e
s
e
nc
e
or
a
b
s
e
nc
e
of
a
nt
ib
a
c
te
r
ia
l
c
om
pounds
c
a
pa
bl
e
of
in
hi
bi
ti
ng
m
ic
r
obi
a
l
gr
ow
th
[
21]
.
T
he
a
nt
ib
a
c
te
r
ia
l
a
c
ti
vi
ty
te
s
t
r
e
s
ul
ts
r
e
ve
a
le
d
th
a
t
in
c
r
e
a
s
in
g
th
e
c
on
c
e
nt
r
a
ti
on
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
in
ha
r
d
c
a
ndy
s
ig
ni
f
ic
a
nt
ly
e
nha
n
c
e
d
th
e
di
a
m
e
te
r
of
th
e
in
hi
bi
ti
on
z
one
s
f
or
St
r
e
pt
oc
oc
c
us
m
ut
ans
a
nd
C
andi
da albi
c
ans
(
p <
0.05)
, a
s
s
how
n i
n F
ig
ur
e
1
.
T
he
da
ta
de
m
on
s
tr
a
te
d
th
a
t
hi
ghe
r
c
onc
e
nt
r
a
ti
ons
of
ba
s
i
l
e
s
s
e
nt
ia
l
oi
l
in
th
e
ha
r
d
c
a
ndy
c
or
r
e
s
ponde
d
to
la
r
ge
r
in
hi
bi
ti
on
z
one
di
a
m
e
te
r
s
.
T
he
r
e
s
ul
ts
in
di
c
a
te
d
th
a
t
th
e
va
r
ia
ti
on
in
ba
s
il
e
s
s
e
nt
ia
l
oi
l
c
onc
e
nt
r
a
ti
ons
s
ig
ni
f
ic
a
nt
ly
a
f
f
e
c
te
d
th
e
in
hi
bi
ti
on
z
one
di
a
m
e
te
r
f
or
St
r
e
pt
oc
oc
c
us
m
ut
an
s
.
T
he
s
tr
e
ngt
h
of
th
e
in
hi
bi
ti
on
z
one
i
s
c
a
t
e
gor
iz
e
d
a
s
w
e
a
k
(
<
5
m
m
)
,
m
ode
r
a
te
(
5
-
10
m
m
)
,
s
tr
ong
(
10
-
20
m
m
)
,
a
nd
ve
r
y
s
tr
ong
(
>
20
m
m
)
[
17]
.
B
a
s
e
d
on
F
ig
ur
e
1
(
a
)
,
a
t
1%
c
onc
e
nt
r
a
ti
on,
th
e
e
s
s
e
nt
ia
l
oi
l
pr
oduc
e
d
th
e
la
r
ge
s
t
in
hi
bi
ti
on
z
one
w
it
h
5.22
m
m
di
a
m
e
te
r
(
m
ode
r
a
te
)
,
w
hi
le
th
e
s
m
a
ll
e
s
t
w
a
s
obs
e
r
ve
d
in
th
e
c
ont
r
ol
(
10%
D
M
S
O
)
,
w
hi
c
h
s
how
e
d
no
c
le
a
r
z
one
.
T
he
D
M
S
O
s
ol
ve
nt
di
d
not
e
xhi
bi
t
a
ny
in
hi
bi
to
r
y
e
f
f
e
c
t,
r
e
s
ul
ti
ng
in
a
n
in
hi
bi
ti
on
z
one
di
a
m
e
te
r
of
0.00
m
m
[
22
]
.
A
t
b
a
s
il
e
s
s
e
nt
ia
l
oi
l
c
onc
e
nt
r
a
ti
ons
of
0,
0.25,
0.5
,
a
nd
0.75%
,
th
e
in
hi
bi
ti
on
z
one
s
a
ga
in
s
t
St
r
e
pt
o
c
oc
c
us
m
ut
ans
w
e
r
e
c
la
s
s
if
ie
d
a
s
w
e
a
k
(
<
5
m
m
)
.
T
he
c
onc
e
nt
r
a
ti
on
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
in
th
e
ha
r
d
c
a
ndy
w
a
s
to
o
lo
w
to
e
f
f
e
c
ti
ve
ly
in
hi
bi
t
St
r
e
pt
oc
oc
c
us
m
ut
ans
.
T
he
a
nt
ib
a
c
te
r
ia
l
e
f
f
e
c
ti
ve
ne
s
s
of
a
c
om
pound
i
s
in
f
lu
e
nc
e
d
b
y
bot
h
it
s
c
on
c
e
nt
r
a
ti
on
a
nd
th
e
ty
pe
of
a
c
ti
ve
s
ubs
ta
nc
e
;
th
u
s
,
th
e
hi
ghe
r
th
e
c
onc
e
nt
r
a
ti
on
of
th
e
a
c
ti
ve
c
o
m
pound,
th
e
gr
e
a
te
r
it
s
e
f
f
e
c
ti
ve
ne
s
s
[
23]
.
T
h
e
in
hi
bi
ti
on
z
one
of
St
r
e
pt
oc
oc
c
us
m
ut
an
s
in
ba
s
il
ha
r
d
c
a
ndy
s
e
e
m
s
to
be
K
ae
m
pf
e
r
ia
gal
anga
L
.,
w
hi
c
h
r
a
nge
s
f
r
om
1.33
to
5.44
m
m
[
13]
.
K
ae
m
pf
e
r
ia
gal
anga
L
.
e
s
s
e
nt
ia
l
oi
l
c
ont
a
in
s
e
th
y
l
p
-
m
e
th
o
x
y
c
in
nam
at
e
,
m
e
th
y
l
c
in
nam
at
e
,
a
nd
pe
nt
ade
c
ane
,
w
hi
c
h
e
xhi
bi
t
a
nt
ib
a
c
te
r
ia
l
a
c
ti
vi
ty
[
13
]
,
w
hi
le
ba
s
il
c
ont
a
in
s
a
lk
a
lo
id
s
,
f
la
vonoids
, t
e
r
pe
noi
ds
, a
nd s
a
poni
n
s
known f
or
t
he
ir
a
nt
ib
a
c
te
r
ia
l
pr
ope
r
ti
e
s
.
B
a
s
e
d
on
th
e
r
e
s
e
a
r
c
h
r
e
s
ul
ts
,
va
r
ia
ti
ons
in
th
e
c
onc
e
nt
r
a
ti
on
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
in
ha
r
d
c
a
ndy
ha
d
a
s
ig
ni
f
ic
a
nt
e
f
f
e
c
t
on
th
e
di
a
m
e
te
r
of
th
e
C
andi
da
al
bi
c
an
s
i
nhi
bi
ti
on
z
one
.
T
he
in
hi
bi
ti
on
z
one
di
a
m
e
t
e
r
s
w
e
r
e
c
la
s
s
if
ie
d a
s
w
e
a
k t
o m
ode
r
a
te
. A
s
s
how
n i
n F
ig
ur
e
1
(
b
)
,
t
he
l
a
r
ge
s
t
in
hi
bi
ti
on z
one
w
a
s
obs
e
r
ve
d a
t
1%
ba
s
il
e
s
s
e
nt
ia
l
oi
l
(
6.11 mm
)
, f
o
ll
ow
e
d by 0.75%
(
5.56 mm
)
, bo
th
of
w
hi
c
h
f
a
ll
w
it
hi
n
th
e
m
ode
r
a
te
c
a
te
gor
y.
T
he
s
m
a
ll
e
s
t
in
hi
bi
ti
on
z
one
w
a
s
r
e
c
or
de
d
in
th
e
c
ont
r
ol
s
a
m
pl
e
(
10%
D
M
S
O
)
,
w
it
h
a
d
ia
m
e
te
r
of
0.00
m
m
.
B
a
s
il
e
s
s
e
nt
ia
l
oi
l
c
onc
e
nt
r
a
ti
ons
of
0,
0.25,
a
nd
0.5%
e
xhi
bi
te
d
w
e
a
k
in
hi
bi
ti
on
(
<
5
m
m
)
a
ga
in
s
t
th
e
g
r
ow
th
of
C
andi
da
al
bi
c
ans
.
T
he
s
e
c
onc
e
nt
r
a
ti
ons
w
e
r
e
li
ke
ly
to
o
l
ow
to
e
f
f
e
c
ti
ve
ly
in
hi
bi
t
f
unga
l
gr
ow
th
.
T
he
va
r
ia
ti
on
in
in
hi
bi
to
r
y
s
tr
e
ngt
h
is
in
f
lu
e
nc
e
d
by
th
e
s
pe
c
i
f
ic
it
y
of
th
e
a
c
ti
ve
c
om
pounds
to
c
e
r
ta
in
m
ic
r
oor
ga
ni
s
m
s
,
th
e
s
us
c
e
pt
ib
il
it
y
of
C
andi
da
al
bi
c
ans
to
ba
s
il
e
s
s
e
nt
ia
l
oi
l
c
om
pone
nt
s
,
a
nd
th
e
c
onc
e
nt
r
a
ti
on
of
a
c
ti
ve
c
om
pounds
us
e
d
[
23]
.
T
he
in
hi
bi
ti
on
z
one
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
a
ga
in
s
t
C
andi
da
al
bi
c
ans
is
gr
e
a
te
r
th
a
n
K
ae
m
pf
e
r
ia
gal
anga
L
.
e
s
s
e
nt
ia
l
oi
l
,
w
hi
c
h
r
a
nge
s
f
r
om
1.44
to
5.56
m
m
[
13]
,
in
di
c
a
ti
ng t
ha
t
ba
s
il
i
s
m
or
e
e
f
f
e
c
ti
ve
i
n i
nhi
bi
ti
ng
C
andi
da albi
c
ans
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
S
N
:
2252
-
8814
I
nt
J
A
dv A
ppl
S
c
i
,
V
ol
.
14
, N
o.
4
,
D
e
c
e
m
be
r
20
25
:
1061
-
1071
1064
(
a
)
(
b)
F
ig
ur
e
1. I
nhi
bi
ti
on z
one
s
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
ha
r
d c
a
ndy
a
ga
i
ns
t
m
ic
r
obi
a
l
gr
ow
th
of
(
a
)
St
r
e
pt
oc
oc
c
us
m
ut
ans
a
nd (
b)
C
andi
da albi
c
ans
F
ig
ur
e
2
il
lu
s
tr
a
te
s
th
a
t
th
e
us
e
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
e
xhi
bi
t
s
s
u
pe
r
io
r
a
nt
ib
a
c
te
r
ia
l
a
c
ti
vi
ty
c
om
pa
r
e
d
to
tr
e
a
tm
e
nt
s
w
it
hout
e
s
s
e
nt
ia
l
oi
l,
a
s
e
vi
de
nc
e
d
by
th
e
s
m
a
ll
e
s
t
in
hi
bi
ti
on
z
one
obs
e
r
ve
d
w
it
h
10%
D
M
S
O
,
w
he
r
e
F
ig
ur
e
2(
a
)
s
how
s
th
e
St
r
e
pt
oc
oc
c
us
m
ut
ans
a
nd
F
ig
ur
e
2(
b)
s
how
s
th
e
C
andi
da
al
bi
c
ans
.
D
M
S
O
,
a
ve
r
s
a
ti
le
or
ga
ni
c
s
ol
ve
nt
c
a
pa
bl
e
of
di
s
s
ol
vi
ng
bot
h
pol
a
r
a
nd
non
-
pol
a
r
c
om
pounds
,
is
not
ba
c
te
r
ic
id
a
l
a
nd
th
us
doe
s
not
in
te
r
f
e
r
e
w
it
h
th
e
a
c
ti
on
of
a
nt
ib
a
c
te
r
ia
l
c
om
pounds
[
24]
.
B
a
s
il
pos
s
e
s
s
e
s
a
nt
ib
a
c
te
r
ia
l
pr
ope
r
ti
e
s
due
to
th
e
pr
e
s
e
nc
e
of
a
lk
a
lo
id
s
,
f
la
vonoids
,
te
r
pe
n
oi
ds
,
a
nd
s
a
poni
ns
[
25]
.
T
e
r
pe
noi
ds
,
s
uc
h
a
s
c
it
r
a
l,
a
r
e
th
e
m
a
in
c
om
pone
nt
s
of
ba
s
il
le
a
f
e
s
s
e
nt
ia
l
oi
l.
T
he
s
e
c
om
pounds
c
a
n
di
s
r
upt
ba
c
te
r
ia
l
c
e
ll
m
e
m
br
a
ne
pe
r
m
e
a
bi
li
ty
,
pr
e
c
ip
it
a
te
pr
ot
e
in
s
,
a
nd
in
a
c
ti
va
t
e
e
nz
ym
a
ti
c
a
c
ti
vi
ty
w
it
hi
n
ba
c
te
r
ia
l
c
e
ll
s
.
A
ddi
ti
ona
ll
y,
e
s
s
e
nt
i
a
l
oi
ls
c
ont
a
in
in
g
hydr
oxyl
(
-
O
H
)
a
nd
c
a
r
bonyl
f
unc
ti
ona
l
gr
oups
e
xhi
bi
t
a
nt
ib
a
c
te
r
ia
l
a
c
ti
vi
ty
by
de
na
tu
r
in
g
pr
o
te
in
s
a
nd
nuc
le
ic
a
c
id
s
,
th
e
r
e
by
di
s
r
upt
in
g
m
e
ta
bol
is
m
or
c
a
us
in
g
c
e
ll
de
a
th
[
26
]
.
A
not
he
r
c
om
pound,
a
lk
a
lo
id
s
,
f
unc
ti
ons
by
in
te
r
f
e
r
in
g
w
it
h
th
e
pe
pt
id
ogl
yc
a
n
c
om
pone
nt
s
of
ba
c
te
r
ia
l
c
e
ll
w
a
ll
s
[
27]
. T
hi
s
di
s
r
upt
io
n pr
e
ve
nt
s
t
he
f
or
m
a
ti
on o
f
a
n i
nt
a
c
t
c
e
ll
w
a
ll
, ul
ti
m
a
te
ly
l
e
a
di
ng
to
c
e
ll
de
a
th
. B
a
s
il
a
ls
o
c
ont
a
in
s
ot
he
r
e
s
s
e
nt
ia
l
oi
l
c
om
pone
nt
s
,
s
u
c
h
a
s
e
u
ge
nol
,
m
e
th
yl
c
ha
vi
c
ol
,
a
nd
te
r
pi
ne
ol
.
T
he
m
e
c
ha
ni
s
m
s
of
e
ug
e
nol
a
nd
te
r
pi
ne
ol
in
c
lu
de
di
s
r
upt
in
g
th
e
out
e
r
ba
c
te
r
ia
l
m
e
m
br
a
ne
,
m
it
oc
hondr
ia
,
a
nd
c
e
ll
ul
a
r
s
tr
uc
tu
r
e
s
[
28]
.
(
a
)
(
b)
F
ig
ur
e
2. I
nhi
bi
ti
on z
one
s
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
ha
r
d c
a
ndy
a
ga
i
ns
t
m
ic
r
obi
a
l
gr
ow
th
of
(
a
)
St
r
e
pt
oc
oc
c
us
m
ut
ans
a
nd (
b)
C
andi
da albi
c
ans
3.2. Con
c
e
n
t
r
at
io
n
in
h
i
b
it
in
g
50%
(
I
C
50
)
an
d
m
in
im
u
m
i
n
h
ib
it
or
y c
on
c
e
n
t
r
at
io
n
IC
50
is
us
e
d
to
de
te
r
m
in
e
th
e
m
in
im
um
c
onc
e
nt
r
a
ti
on
of
a
n
a
nt
ib
a
c
te
r
ia
l
s
ol
ut
io
n
r
e
qui
r
e
d
to
in
hi
bi
t
50%
of
th
e
gr
ow
th
of
a
s
pe
c
if
ic
ba
c
te
r
iu
m
.
T
he
M
I
C
in
di
c
a
t
e
s
t
he
m
in
im
um
c
onc
e
nt
r
a
ti
on
of
a
n
a
nt
ib
a
c
t
e
r
ia
l
s
ol
ut
io
n
ne
c
e
s
s
a
r
y
to
ki
ll
a
s
pe
c
if
ic
ba
c
te
r
iu
m
[
29]
.
T
he
lo
ga
r
it
hm
ic
c
ur
ve
s
,
s
how
n
in
F
ig
ur
e
3,
de
pi
c
t
th
e
r
e
la
ti
ons
hi
p be
twe
e
n t
he
l
og of
c
ol
ony c
ount
a
nd t
he
c
on
c
e
nt
r
a
t
io
n of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
in
ha
r
d c
a
ndy.
B
a
s
e
d
on
F
ig
ur
e
3,
th
e
lo
g
a
r
it
hm
ic
c
ur
ve
e
qua
ti
ons
di
s
pl
a
y
a
li
ne
a
r
tr
e
nd,
w
he
r
e
hi
ghe
r
c
onc
e
nt
r
a
ti
ons
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
c
or
r
e
s
pond to a
l
ow
e
r
l
og o
f
ba
c
te
r
ia
l
c
ol
ony c
ount
. C
a
lc
ul
a
ti
ons
r
e
ve
a
le
d
th
a
t
th
e
I
C
50
of
ha
r
d
c
a
ndy
f
or
St
r
e
pt
oc
oc
c
us
m
ut
ans
gr
ow
th
w
a
s
1.614
m
g/
m
l
,
a
s
s
how
n
in
F
ig
ur
e
3(
a
)
.
A
t
a
ba
s
il
e
s
s
e
nt
ia
l
oi
l
c
onc
e
nt
r
a
ti
on
of
1.614
m
g/
m
L
,
th
e
ha
r
d
c
a
ndy
in
hi
bi
te
d
50%
of
ba
c
te
r
ia
l
g
r
ow
th
(
I
C
50
)
.
T
he
M
I
C
va
lu
e
w
a
s
d
e
te
r
m
in
e
d t
o be
5.362 mg/
m
L
, i
ndi
c
a
ti
ng t
ha
t
th
is
c
onc
e
nt
r
a
ti
on w
a
s
r
e
qui
r
e
d t
o a
c
hi
e
v
e
0.00
1.00
b
1.89
c
3.11
d
4.11
e
5.22
f
0
1
2
3
4
5
6
7
D
M
S
O
10%
0%
0
.2
5
%
0
.5
0
%
0.75%
1%
C
l
e
ar
Z
on
e
D
i
am
e
t
e
r
(
m
m
)
E
s
s
e
n
t
i
aol
s
oi
l
on
h
ar
d
c
an
d
y
0.00
1.00
b
1.78
c
3.33
d
5.56
e
6.11
e
0
1
2
3
4
5
6
7
D
M
S
O
10%
0%
0.25%
0.50%
0.75%
1%
C
l
e
ar
Z
on
e
D
i
am
e
t
e
r
(
m
m
)
C
on
c
e
n
t
r
at
i
on
of
B
as
i
l
E
s
s
e
n
t
i
al
O
i
l
i
n
H
ar
d
C
an
d
y
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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J
A
dv A
ppl
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i
I
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2252
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8814
A
nt
imi
c
r
obi
al
ac
ti
v
it
y
of
har
d c
andy
w
it
h bas
il
(
O
c
imum
s
ant
c
t
um
L
.)
e
s
s
e
nt
ia
l
oi
l
addi
ti
on
(
M
ar
ia
B
e
lg
is
)
1065
c
om
pl
e
te
i
nhi
bi
ti
on of
St
r
e
pt
oc
oc
c
us
m
ut
ans
gr
ow
th
. C
a
lc
ul
a
ti
ons
r
e
ve
a
le
d t
ha
t
th
e
I
C
50
f
or
C
andi
da albi
c
ans
gr
ow
th
w
a
s
2.078
m
g
/ml
,
a
s
s
ho
w
n
in
F
ig
ur
e
3(
b)
.
A
t
a
ba
s
il
e
s
s
e
nt
ia
l
oi
l
c
onc
e
nt
r
a
ti
on
of
2.078
m
g/
m
L
,
th
e
ha
r
d c
a
ndy inhi
bi
te
d 50%
of
C
andi
da albi
c
ans
gr
ow
th
(
I
C
50
).
(
a
)
(
b)
F
ig
ur
e
3. I
nhi
bi
ti
on c
ur
ve
of
ba
s
il
e
s
s
e
nt
ia
l
oi
l
ha
r
d c
a
ndy a
ga
in
s
t
th
e
gr
ow
th
of
(
a
)
St
r
e
pt
oc
oc
c
us
m
ut
ans
a
nd
(
b)
C
andi
da albi
c
ans
3.3. I
d
e
n
t
if
ic
at
io
n
of
vol
at
il
e
c
om
p
on
e
n
t
s
T
he
vol
a
ti
le
c
om
pone
nt
s
id
e
nt
if
ie
d
in
ba
s
il
h
a
r
d
c
a
ndy
a
r
e
pr
e
s
e
nt
e
d
in
T
a
bl
e
1
(
s
e
e
in
A
ppe
ndi
x
)
.
T
he
id
e
nt
if
ic
a
ti
on
r
e
s
ul
ts
obt
a
in
e
d
th
r
ough
ga
s
c
hr
om
a
to
g
r
a
phy
-
m
a
s
s
s
pe
c
tr
om
e
tr
y
(
GC
-
MS
)
a
na
ly
s
is
r
e
ve
a
le
d
s
e
ve
r
a
l
c
om
pounds
,
in
c
lu
di
ng
li
na
lo
ol
,
e
uge
nol
,
c
a
r
yophyll
e
ne
,
a
nd
tr
a
ns
-
α
-
be
r
ga
m
ot
e
ne
.
C
a
r
yophyll
e
ne
w
a
s
de
te
c
te
d
in
r
e
la
ti
ve
ly
hi
gh
a
m
ount
s
.
L
in
a
l
ool
is
a
n
a
c
ti
ve
a
nt
im
ic
r
obi
a
l
c
om
pound
[
30]
.
A
s
a
te
r
pe
noi
d
a
lc
ohol
,
it
e
xhi
bi
ts
ba
c
te
r
ic
id
a
l
a
c
ti
vi
ty
a
ga
i
ns
t
ve
ge
ta
ti
ve
c
e
ll
s
[
31]
.
S
im
il
a
r
ly
,
e
uge
nol
de
m
ons
tr
a
te
s
a
nt
im
ic
r
obi
a
l
a
c
ti
vi
ty
a
ga
in
s
t
St
r
e
pt
oc
o
c
c
us
m
u
ta
ns
[
32]
.
C
a
r
yophyll
e
ne
ha
s
be
e
n
s
how
n
to
pos
s
e
s
s
a
nt
ib
a
c
te
r
ia
l,
a
nt
io
xi
da
nt
,
a
nt
if
unga
l,
a
nd
pot
e
nt
c
yt
ot
oxi
c
pr
ope
r
ti
e
s
[
33]
.
T
r
a
ns
-
α
-
be
r
ga
m
ot
e
ne
a
ls
o
e
xhi
bi
ts
a
nt
im
ic
r
obi
a
l
a
c
ti
vi
ty
,
e
f
f
e
c
ti
ve
ly
ta
r
ge
ti
ng
m
ic
r
obe
s
s
uc
h
a
s
St
r
e
pt
oc
o
c
c
us
m
ut
ans
a
nd
C
andi
da
al
bi
c
ans
.
A
ddi
ti
ona
ll
y,
it
is
pa
r
ti
c
ul
a
r
ly
e
f
f
e
c
ti
ve
a
ga
in
s
t
gr
a
m
-
pos
it
iv
e
ba
c
te
r
ia
,
in
c
lu
di
ng
St
r
e
pt
oc
oc
c
us
al
bus
, a
nd f
ungi
s
uc
h a
s
A
s
p
e
r
gi
ll
us
ni
ge
r
[
34]
.
3.4. P
r
e
f
e
r
e
n
c
e
s
3.4.1. Color
C
ol
or
pl
a
ys
a
n
im
por
ta
nt
r
ol
e
in
th
e
pr
e
s
e
nt
a
ti
on
of
a
f
o
od
pr
oduc
t
to
de
te
r
m
in
e
c
ons
um
e
r
a
c
c
e
pt
a
nc
e
.
C
on
s
um
e
r
s
te
nd
to
be
a
tt
r
a
c
te
d
to
f
ood
pr
oduc
ts
w
it
h
a
ppe
a
li
ng
c
ol
or
s
[
35]
.
B
a
s
e
d
on
th
e
da
ta
f
r
om
t
he
pr
e
f
e
r
e
nc
e
t
e
s
t
of
ba
s
il
ha
r
d c
a
ndy c
ol
or
s
how
n i
n F
ig
ur
e
4. T
he
a
ddi
ti
on of
0.75%
ba
s
il
e
s
s
e
nt
ia
l
oi
l
in
th
e
ha
r
d
c
a
ndy
tr
e
a
tm
e
nt
r
e
s
ul
te
d
in
th
e
hi
ghe
s
t
m
e
a
s
ur
e
d
c
o
lo
r
va
lu
e
of
69%
.
T
he
c
ol
or
of
th
e
ha
r
d
c
a
ndy
is
in
f
lu
e
nc
e
d
by
th
e
c
onc
e
nt
r
a
ti
on
of
th
e
a
dd
e
d
e
s
s
e
nt
ia
l
oi
l.
T
he
hi
ghe
r
th
e
c
on
c
e
nt
r
a
ti
on,
th
e
m
or
e
in
te
n
s
e
th
e
r
e
s
ul
ti
ng c
ol
or
[
36]
.
F
ig
ur
e
4. P
e
r
c
e
nt
a
ge
of
ha
r
d c
a
ndy c
ol
or
a
c
c
e
pt
a
nc
e
3.4.2. Ar
om
a
A
r
om
a
is
a
n
im
por
ta
nt
in
di
c
a
to
r
in
f
ood
pr
oduc
ts
a
s
it
c
a
n
de
t
e
r
m
in
e
w
he
th
e
r
a
pr
oduc
t
is
a
c
c
e
pt
e
d
or
not
[
36]
.
B
a
s
e
d
on
th
e
da
ta
f
r
om
th
e
pr
e
f
e
r
e
nc
e
te
s
t
of
ba
s
il
ha
r
d
c
a
ndy
a
r
om
a
,
s
how
n
in
F
ig
ur
e
5.
T
he
a
ddi
ti
on
of
0.75%
ba
s
il
e
s
s
e
nt
ia
l
oi
l
in
th
e
ha
r
d
c
a
ndy
r
e
s
ul
te
d
in
th
e
hi
ghe
s
t
a
r
om
a
s
c
or
e
of
57%
.
T
h
e
m
or
e
ba
s
il
e
s
s
e
nt
ia
l
oi
l
a
dde
d
to
th
e
ha
r
d
c
a
ndy,
th
e
s
tr
onge
r
th
e
c
ha
r
a
c
te
r
is
ti
c
ba
s
il
a
r
om
a
.
T
hi
s
di
s
ti
nc
ti
ve
a
r
om
a
is
a
tt
r
ib
ut
e
d
to
th
e
pr
e
s
e
nc
e
of
s
e
v
e
r
a
l
vol
a
ti
le
c
om
pound
s
in
t
he
e
s
s
e
nt
ia
l
oi
l
,
a
s
s
how
n
in
T
a
bl
e
1.
S
om
e
of
th
e
s
e
c
om
pound
s
in
c
lu
de
c
in
e
ol
e
,
e
ug
e
nol
,
a
nd
ot
he
r
s
.
T
he
a
r
om
a
of
th
e
ha
r
d
c
a
ndy
in
th
is
s
tu
dy
is
in
f
lu
e
nc
e
d by the
vol
a
ti
le
c
om
pounds
pr
e
s
e
nt
i
n t
he
ba
s
il
e
s
s
e
nt
ia
l
oi
l
a
dde
d dur
in
g
t
he
pr
oc
e
s
s
in
g s
ta
ge
[
37]
.
T
he
ba
s
il
pl
a
nt
c
ont
a
in
s
e
s
s
e
nt
ia
l
oi
ls
th
a
t
im
pa
r
t
a
uni
que
t
a
s
te
a
nd
a
r
om
a
[
38]
.
B
a
s
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le
a
f
e
s
s
e
nt
ia
l
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20
25
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pr
im
a
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r
a
ni
a
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(
E
-
c
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43.74%
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,
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r
a
l
(
Z
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it
r
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31.19%
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,
li
na
lo
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(
7.03%
)
,
ne
r
ol
(
6.93%
)
,
a
nd ge
r
a
ni
ol
(
4.62%
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.
F
ig
ur
e
5. P
e
r
c
e
nt
a
ge
of
ha
r
d c
a
ndy a
r
om
a
a
c
c
e
pt
a
n
c
e
3.4.3. T
as
t
e
T
a
s
te
is
on
e
of
th
e
f
a
c
to
r
s
th
a
t
de
te
r
m
in
e
s
th
e
qua
li
ty
of
f
ood. B
a
s
e
d
on
th
e
da
ta
f
r
om
th
e
pr
e
f
e
r
e
nc
e
te
s
t
f
or
th
e
ta
s
te
of
b
a
s
il
ha
r
d
c
a
ndy,
s
how
n
in
F
ig
ur
e
6.
T
he
h
a
r
d
c
a
ndy
f
or
m
ul
a
ti
on
c
ont
a
in
in
g
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ba
s
il
e
s
s
e
nt
ia
l
oi
l
s
how
e
d
th
e
hi
ghe
s
t
ta
s
te
s
c
or
e
,
a
t
47%
.
T
hi
s
oc
c
u
r
r
e
d
be
c
a
us
e
th
e
a
ddi
ti
on
of
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il
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s
s
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nt
ia
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oi
l
a
t
a
0.25%
c
onc
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nt
r
a
ti
on
w
a
s
m
in
im
a
l,
th
us
not
ove
r
pow
e
r
in
g
th
e
c
ha
r
a
c
te
r
is
ti
c
ba
s
il
ta
s
t
e
,
m
a
ki
ng
it
a
c
c
e
pt
a
bl
e
to
th
e
pa
n
e
li
s
ts
.
T
he
di
s
ti
nc
ti
ve
b
a
s
il
f
la
vor
in
th
e
ba
s
il
e
s
s
e
nt
ia
l
oi
l
ha
r
d
c
a
ndy
is
in
f
lu
e
nc
e
d
by
th
e
c
om
pounds
c
ont
a
in
e
d
in
th
e
b
a
s
il
e
s
s
e
nt
ia
l
oi
l.
T
he
e
s
s
e
nt
ia
l
oi
l
c
om
pos
it
io
n
in
th
e
ba
s
il
pl
a
nt
de
te
r
m
in
e
s
th
e
s
pe
c
if
ic
a
r
om
a
a
nd
f
la
vor
of
th
e
he
r
b
[
39]
.
T
he
hi
gh
e
r
th
e
c
onc
e
nt
r
a
ti
on
of
e
s
s
e
nt
ia
l
oi
l
a
dd
e
d,
th
e
s
tr
onge
r
t
he
c
ha
r
a
c
te
r
is
ti
c
ba
s
il
t
a
s
te
be
c
om
e
s
.
F
ig
ur
e
6. B
a
r
c
ha
r
t
of
t
he
pe
r
c
e
nt
a
ge
of
t
a
s
te
a
c
c
e
pt
a
nc
e
3.4.4. Over
al
l
O
ve
r
a
ll
pr
e
f
e
r
e
nc
e
is
a
n
a
s
s
e
s
s
m
e
nt
c
ondu
c
te
d
on
a
ll
or
ga
nol
e
p
ti
c
qua
li
ty
pa
r
a
m
e
te
r
s
,
na
m
e
ly
c
ol
or
,
a
r
om
a
,
a
nd
ta
s
te
.
T
he
or
ga
nol
e
pt
ic
c
ha
r
a
c
te
r
is
ti
c
s
of
ba
s
il
ha
r
d
c
a
ndy
te
s
te
d
in
th
is
s
tu
dy
w
e
r
e
ge
ne
r
a
ll
y
a
c
c
e
pt
a
bl
e
to
th
e
pa
ne
li
s
t
s
.
B
a
s
e
d
on
th
e
da
ta
f
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om
th
e
pr
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f
e
r
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nc
e
te
s
t
f
or
th
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ove
r
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ll
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il
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r
d
c
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how
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in
F
ig
ur
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7,
th
e
ha
r
d
c
a
ndy
s
a
m
pl
e
w
it
h
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s
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s
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nt
ia
l
o
il
w
a
s
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vor
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d
by
th
e
pa
ne
li
s
ts
. T
hi
s
in
di
c
a
te
s
th
a
t
th
e
pa
ne
li
s
ts
pr
e
f
e
r
r
e
d
th
e
ha
r
d
c
a
ndy
w
it
h
a
m
ode
r
a
te
a
m
ount
of
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il
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s
s
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nt
ia
l
oi
l,
not
to
o
li
tt
le
nor
to
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m
uc
h.
F
r
om
th
e
s
e
ns
or
y
da
ta
a
bove
,
it
c
a
n
be
c
onc
lu
de
d
th
a
t
th
e
pa
ne
li
s
ts
'
ove
r
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ll
pr
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e
r
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e
f
or
c
ol
or
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a
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om
a
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ig
ni
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ic
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nt
ly
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ove
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pr
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t.
A
ddi
ti
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y,
if
th
e
r
e
a
r
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a
ny f
a
c
to
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t
a
r
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l
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s
f
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vor
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d, i
t
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ove
r
a
ll
a
c
c
e
pt
a
nc
e
of
t
he
pa
n
e
li
s
ts
[
39]
.
F
ig
ur
e
7. O
ve
r
a
ll
ha
r
d c
a
ndy a
c
c
e
pt
a
nc
e
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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J
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3.5. E
f
f
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c
t
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s
s
val
u
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T
he
e
f
f
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c
ti
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te
s
t
w
a
s
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onduc
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to
de
te
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m
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s
t
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on
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te
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p
a
r
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lu
e
in
di
c
a
te
s
th
e
b
e
s
t
s
a
m
pl
e
[
20]
.
T
he
b
e
s
t
tr
e
a
tm
e
nt
in
th
e
pr
oduc
ti
on
of
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yi
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onc
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r
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ti
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b
a
s
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d
on
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ul
ts
of
th
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doni
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te
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t
s
,
w
hi
c
h
in
c
lu
de
c
ol
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,
a
r
om
a
,
ta
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,
ove
r
a
ll
pr
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f
e
r
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n
c
e
,
a
nd
th
e
in
hi
bi
ti
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z
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t
(
di
s
k
m
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th
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.
T
he
hi
ghe
r
th
e
le
ve
l
of
i
m
por
ta
nc
e
, t
he
hi
ghe
r
t
he
w
e
ig
ht
va
lu
e
a
s
s
ig
ne
d t
o t
he
va
r
ia
bl
e
[
20]
.
T
a
bl
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2
s
how
s
th
a
t
th
e
ha
r
d
c
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ndy
s
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it
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th
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b
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a
t
m
e
nt
,
w
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c
h
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vol
ve
d
th
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ddi
ti
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of
0.75%
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s
s
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nt
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l
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r
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ul
te
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a
n
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f
f
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ve
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s
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of
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r
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a
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it
h
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s
s
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l
ha
d
or
ga
nol
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pt
ic
va
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s
(
s
om
e
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h
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t
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ke
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to
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y
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d)
f
or
th
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or
pa
r
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te
r
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t
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a
a
t
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t
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r
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t
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nt
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a
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te
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ty
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in
s
t
St
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C
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c
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w
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(
m
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te
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s
pe
c
ti
ve
ly
.
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a
bl
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2.
T
he
e
f
f
e
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ti
ve
ne
s
s
va
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e
of
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s
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r
d c
a
nd
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C
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t
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(
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f
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ve
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va
l
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0.25
0.32
0.50
0.60
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1.00
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4.
C
O
N
C
L
U
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I
O
N
T
he
hi
ghe
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ba
s
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e
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c
r
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s
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s
a
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li
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th
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pt
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u
s
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a
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C
andi
da
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c
ans
gr
ow
th
.
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he
be
s
t
tr
e
a
tm
e
nt
w
a
s
a
t
0.75%
c
onc
e
nt
r
a
ti
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w
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r
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th
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c
a
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how
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t
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s
how
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f
f
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T
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c
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ound the
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a
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ts
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how
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it
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S
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ovi
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de
r
a
l
F
ood, Dr
ug, a
nd C
os
m
e
ti
c
A
c
t
. F
D
A
, 2017
.
–
I
ns
ti
tu
te
of
F
ood
S
c
ie
nc
e
&
T
e
c
hnol
ogy.
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ui
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li
ne
s
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or
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ic
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l
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ti
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e
S
e
ns
or
y A
na
ly
s
is
of
F
oods
. I
F
ST
, 2020.
D
A
T
A
A
V
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L
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B
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L
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T
Y
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E
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E
R
E
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C
E
S
[
1]
K
.
A
l
m
a
s
a
nd
Z
.
A
.
-
Z
e
i
d,
“
T
he
i
m
m
e
di
a
t
e
a
nt
i
m
i
c
r
obi
a
l
e
f
f
e
c
t
of
a
t
oot
hbr
us
h
a
nd
m
i
s
w
a
k
on
c
a
r
i
oge
ni
c
ba
c
t
e
r
i
a
:
a
c
l
i
ni
c
a
l
s
t
udy,”
T
he
J
our
nal
of
C
ont
e
m
por
ar
y
D
e
nt
al
P
r
ac
t
i
c
e
, vol
. 5, no. 1, pp. 105
–
11
4, F
e
b. 2004, doi
:
10.5005/
j
c
dp
-
5
-
1
-
105.
[
2]
J
.
R
.
C
or
t
e
l
l
i
,
M
.
D
.
S
.
B
a
r
bos
a
,
a
nd
M
.
A
.
W
e
s
t
pha
l
,
“
H
a
l
i
t
os
i
s
:
a
r
e
vi
e
w
of
a
s
s
oc
i
a
t
e
d
f
a
c
t
or
s
a
nd
t
he
r
a
pe
ut
i
c
a
ppr
oa
c
h,”
B
r
az
i
l
i
an O
r
al
R
e
s
e
ar
c
h
, vol
. 22, no. s
uppl
1, pp. 44
–
54, A
ug. 2008, doi
:
10.15
90/
S
1806
-
83242008000500007.
[
3]
V
. I
. F
a
t
m
a
s
a
r
i
,
R
. H
a
ps
a
r
i
, N
.
H
a
r
di
ni
, a
nd
E
. S
.
L
e
s
t
a
r
i
,
“
T
he
e
f
f
e
c
t
of
V
C
O
t
o t
he
gr
ow
t
h of
C
andi
da al
bi
c
an
s
on
de
nt
ur
e
ba
s
i
s
of
a
c
r
yl
i
c
r
e
s
i
n,”
D
i
pone
gor
o
M
e
di
c
al
J
our
nal
(
J
ur
nal
K
e
dok
t
e
r
an
D
i
pone
gor
o)
,
vol
.
9,
no.
6,
pp.
442
–
447,
N
ov.
2020,
doi
:
10.14710/
dm
j
.v9i
6.29329.
[
4]
C
.
A
.
K
um
a
m
ot
o
a
nd
M
.
D
.
V
i
nc
e
s
,
“
A
l
t
e
r
na
t
i
ve
C
andi
da
al
bi
c
ans
l
i
f
e
s
t
yl
e
s
:
gr
ow
t
h
on
s
ur
f
a
c
e
s
,”
A
nnual
R
e
v
i
e
w
of
M
i
c
r
obi
ol
ogy
, vol
. 59, no. 1, pp. 113
–
133, O
c
t
. 2005, doi
:
10.1146/
a
nnur
e
v.m
i
c
r
o.59.030804.121034.
[
5]
N
.
S
a
hoo,
R
.
K
.
S
a
hoo,
N
.
B
i
s
w
a
s
,
A
.
G
uha
,
a
nd
K
.
K
uot
s
u,
“
R
e
c
e
nt
a
dva
nc
e
m
e
nt
of
ge
l
a
t
i
n
na
nopa
r
t
i
c
l
e
s
i
n
dr
ug
a
nd
v
a
c
c
i
n
e
de
l
i
ve
r
y,”
I
nt
e
r
nat
i
onal
J
our
nal
of
B
i
o
l
ogi
c
al
M
ac
r
om
ol
e
c
ul
e
s
,
vol
.
81,
pp.
317
–
331,
N
ov.
2015,
doi
:
10.1016/
j
.i
j
bi
om
a
c
.2015.08.006.
[
6]
D
.
R
ubi
ya
nt
o
a
nd
D
.
F
i
t
r
i
ya
h,
“
I
s
ol
a
t
i
on
of
C
I
S
-
a
nd
t
r
a
ns
-
s
i
t
r
a
l
s
f
r
om
B
a
s
i
l
e
s
s
e
nt
i
a
l
oi
l
(
O
c
i
m
um
C
i
t
r
i
odor
um
,
L
)
w
i
t
h
bi
s
ul
f
i
t
e
xt
r
a
c
t
i
on
m
e
t
hod
a
nd
s
t
e
a
m
di
s
t
i
l
l
a
t
i
on
m
e
t
hod,”
I
ndone
s
i
an
J
our
nal
of
E
s
s
e
nt
i
al
O
i
l
,
vol
.
1,
no.
1,
pp.
1
–
11,
N
ov.
2016,
doi
:
10.21776/
ub.i
j
e
o.2016.001.01.01.
[
7]
M
.
M
.
G
.
-
P
a
c
he
c
o
e
t
al
.
,
“
M
e
c
ha
ni
s
m
s
a
nd
a
ppl
i
c
a
t
i
ons
of
c
i
t
r
a
l
’
s
a
nt
i
m
i
c
r
obi
a
l
pr
ope
r
t
i
e
s
i
n
f
ood
pr
e
s
e
r
va
t
i
on
a
nd
pha
r
m
a
c
e
ut
i
c
a
l
s
f
or
m
ul
a
t
i
ons
,”
A
nt
i
bi
ot
i
c
s
, vol
. 12, no. 11, N
ov. 2023, doi
:
10.3390/
a
nt
i
bi
ot
i
c
s
12111608.
[
8]
S
.
G
a
o
e
t
al
.
,
“
A
nt
i
m
i
c
r
obi
a
l
a
c
t
i
vi
t
y
of
l
e
m
ongr
a
s
s
e
s
s
e
nt
i
a
l
oi
l
(
C
y
m
bopogo
n
f
l
e
x
uos
u
s
)
a
nd
i
t
s
a
c
t
i
ve
c
om
pone
nt
c
i
t
r
a
l
a
ga
i
ns
t
dua
l
-
s
pe
c
i
e
s
bi
of
i
l
m
s
of
S
t
a
phyl
oc
oc
c
us
a
ur
e
us
a
nd
C
a
ndi
da
s
pe
c
i
e
s
,”
F
r
ont
i
e
r
s
i
n
C
e
l
l
ul
ar
and
I
nf
e
c
t
i
on
M
i
c
r
obi
ol
ogy
,
vol
.
10,
D
e
c
. 2020, doi
:
10.3389/
f
c
i
m
b.2020.603858.
[
9]
S
.
T
ha
w
e
boon
a
nd
B
.
T
ha
w
e
boon,
“
I
n
vi
t
r
o
a
nt
i
m
i
c
r
ob
i
a
l
a
c
t
i
vi
t
y
of
O
c
i
m
um
am
e
r
i
c
anum
L
.
e
s
s
e
nt
i
a
l
oi
l
a
ga
i
ns
t
or
a
l
m
i
c
r
oor
ga
ni
s
m
s
,”
Sout
he
as
t
A
s
i
an j
our
nal
of
t
r
opi
c
al
m
e
di
c
i
ne
and publ
i
c
he
al
t
h
, vol
. 40, no. 5, pp. 1025
–
1033, 2009.
[
10]
G
.
O
pa
l
c
he
nova
a
nd
D
.
O
br
e
s
hkova
,
“
C
om
pa
r
a
t
i
ve
s
t
udi
e
s
on
t
he
a
c
t
i
vi
t
y
of
ba
s
i
l
—
a
n
e
s
s
e
nt
i
a
l
oi
l
f
r
om
O
c
i
m
um
bas
i
l
i
c
um
L.
—
a
ga
i
ns
t
m
ul
t
i
dr
ug
r
e
s
i
s
t
a
nt
c
l
i
ni
c
a
l
i
s
ol
a
t
e
s
of
t
he
ge
ne
r
a
S
t
a
phyl
oc
oc
c
u
s
,
E
nt
e
r
oc
oc
c
us
a
nd
P
s
e
udom
ona
s
by
us
i
ng
di
f
f
e
r
e
nt
t
e
s
t
m
e
t
hods
,”
J
our
nal
of
M
i
c
r
obi
ol
ogi
c
al
M
e
t
hods
, vol
. 54, no. 1, pp. 105
–
110, J
ul
. 2003, doi
:
10.1016/
S
0167
-
7012(
03
)
00012
-
5.
[
11]
R
.
W
.
H
a
r
t
e
l
,
J
.
H
.
v
.
E
l
be
,
a
nd
R
.
H
of
be
r
ge
r
,
“
H
a
r
d
C
a
ndy,”
i
n
C
onf
e
c
t
i
one
r
y
Sc
i
e
nc
e
and
T
e
c
hnol
ogy
,
C
h
a
m
:
S
pr
i
nge
r
I
nt
e
r
na
t
i
ona
l
P
ubl
i
s
hi
ng, 2018, pp. 211
–
244. doi
:
10.1007/
978
-
3
-
319
-
61742
-
8_
8.
[
12]
M
.
B
e
l
gi
s
,
G
i
ya
r
t
o,
M
.
M
.
F
e
br
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.
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.
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a
vi
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i
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.
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.
R
u
s
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o,
“
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e
ns
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y
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ha
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a
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i
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i
c
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nd
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nt
i
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i
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obi
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i
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i
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i
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um
Sanc
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L
.)
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ga
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t
C
an
di
da
al
bi
c
ans
a
nd
St
r
e
pt
oc
oc
c
u
s
m
ut
ans
,
”
J
our
na
l
L
a L
i
f
e
s
c
i
, vol
. 3, no. 3, pp. 108
–
118, N
ov. 2022, doi
:
10.37899/
j
our
na
l
l
a
l
i
f
e
s
c
i
.v3i
3.701.
[
13]
M
.
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e
l
gi
s
,
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.
N
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f
i
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,
G
.
G
i
ya
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t
o,
a
nd
A
.
D
.
W
ul
a
nda
r
i
,
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A
nt
i
ba
c
t
e
r
i
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l
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t
y
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ae
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al
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a
phyl
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oc
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us
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ur
e
us
ba
c
t
e
r
i
a
gr
ow
t
h,”
I
nt
e
r
nat
i
onal
J
our
nal
on
F
ood,
A
gr
i
c
ul
t
ur
e
and
N
at
ur
a
l
R
e
s
our
c
e
s
, vol
. 2, no. 1, pp. 1
–
8, M
a
y 2021, doi
:
10.46676/
i
j
-
f
a
nr
e
s
.v2i
1.22.
[
14]
J
.
J
ul
i
a
ni
,
I
.
I
r
m
a
ya
nt
i
,
a
nd
M
.
D
.
A
K
,
“
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ol
ubi
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t
y
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nd
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nt
i
m
i
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l
a
c
t
i
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y
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y
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r
i
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am
a)
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nd
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ul
a
t
i
on
of
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t
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houl
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l
(
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ogos
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e
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on
c
ab
l
i
n
B
e
nt
h
)
ba
s
e
d
e
s
s
e
nt
i
a
l
oi
l
s
,”
J
ur
nal
M
e
di
k
a
V
e
t
e
r
i
nar
i
a
, vol
. 18, no. 2, A
ug. 2024, doi
:
10.21157/
j
.m
e
d.ve
t
..v18i
2.36472.
[
15]
S
.
S
oe
ka
r
no,
S
.
D
.
H
e
r
na
nt
o,
D
.
P
ur
ba
s
a
r
i
,
a
nd
D
.
M
e
l
a
ni
,
“
S
t
udy
o
f
di
s
t
i
l
l
a
t
i
o
n
m
e
t
hod
a
nd
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i
m
e
on
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he
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l
i
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y
of
ba
s
i
l
(
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c
i
m
um
s
anc
t
um
L.
)
e
s
s
e
nt
i
a
l
oi
l
,”
J
ur
nal
T
e
k
ni
k
P
e
r
t
ani
an
L
am
pung
(
J
our
nal
of
A
g
r
i
c
ul
t
ur
al
E
ngi
ne
e
r
i
ng)
,
vol
.
13,
no.
2,
J
un.
2024,
doi
:
10.23960/
j
t
e
p
-
l
.v13i
2.606
-
614.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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ia
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(
M
ar
ia
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e
lg
is
)
1069
[
16]
S
.
M
a
ul
i
z
a
a
nd
G
.
I
.
D
a
l
i
m
unt
he
,
“
F
o
r
m
ul
a
t
i
on
a
nd
e
va
l
ua
t
i
on
o
f
t
he
p
r
e
pa
r
a
t
i
on
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d
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ndy
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our
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e
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s
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.)
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c
k)
a
s
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nut
r
a
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e
t
i
c
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l
,”
I
nt
e
r
nat
i
onal
J
our
nal
of
Sc
i
e
nc
e
,
T
e
c
hnol
ogy
&
M
anage
m
e
nt
,
vol
.
3,
no.
5,
pp. 1465
–
1470, S
e
p. 2022, doi
:
10.46729/
i
j
s
t
m
.v3i
5.611.
[
17]
G
.
M
or
a
l
e
s
e
t
al
.
,
“
S
e
c
onda
r
y
m
e
t
a
bol
i
t
e
s
f
r
om
f
our
m
e
di
c
i
na
l
pl
a
nt
s
f
r
om
N
or
t
he
r
n
C
hi
l
e
:
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nt
i
m
i
c
r
obi
a
l
a
c
t
i
vi
t
y
a
nd
bi
ot
oxi
c
i
t
y
a
ga
i
ns
t
A
r
t
e
m
i
a
s
a
l
i
na
,”
J
our
nal
of
t
he
C
hi
l
e
an
C
he
m
i
c
al
Soc
i
e
t
y
, vol
. 48, no. 2
, 2003, doi
:
10.4067/
S
0717
-
97072003000200002.
[
18]
H.
-
A
.
C
hoi
e
t
al
.
,
“
A
nt
i
m
i
c
r
obi
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l
a
nd
a
nt
i
-
bi
of
i
l
m
a
c
t
i
vi
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e
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he
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e
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ha
nol
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e
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a
nt
s
a
ga
i
ns
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de
nt
a
l
p
a
t
hoge
n
s
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r
e
pt
oc
oc
c
u
s
m
ut
ans
a
nd
C
andi
da
al
bi
c
an
s
,”
J
our
nal
of
M
i
c
r
obi
ol
ogy
an
d
B
i
ot
e
c
hnol
ogy
,
vol
.
27,
no.
7,
pp.
1242
–
1248,
J
ul
. 2017, doi
:
10.4014/
j
m
b.1701.01026.
[
19]
L
. S
e
l
va
kum
a
r
a
n,
R
. S
hukr
i
, N
.
S
. R
a
m
l
i
,
M
.
S
. P
a
k D
e
k, a
nd
W
. Z
.
W
. I
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dul
l
a
h, “
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r
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nge
s
w
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e
t
pot
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o
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pom
oe
a bat
at
as
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pur
e
e
i
m
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ove
d phys
i
c
oc
he
m
i
c
a
l
pr
ope
r
t
i
e
s
a
nd
s
e
n
s
or
y a
c
c
e
pt
a
nc
e
of
br
ow
ni
e
s
,”
J
o
ur
nal
of
t
he
Saudi
Soc
i
e
t
y
of
A
gr
i
c
ul
t
ur
al
Sc
i
e
nc
e
s
,
vol
. 18, no. 3, pp. 332
–
336, J
ul
. 2019, doi
:
10.1016/
j
.j
s
s
a
s
.2017.09.006.
[
20]
E
.
P
.
D
e
G
a
r
m
o,
“
I
ndus
t
r
y’
s
us
e
a
nd
e
va
l
ua
t
i
on
of
t
he
i
m
por
t
a
nc
e
of
e
ngi
ne
e
r
i
ng
e
c
onom
y
,”
T
he
E
ngi
ne
e
r
i
ng
E
c
onom
i
s
t
,
vol
.
10
,
no. 1, pp. 1
–
10, J
a
n. 1965, doi
:
10.1080/
00137916408928706.
[
21]
M
.
B
a
l
oui
r
i
,
M
.
S
a
di
ki
,
a
nd
S
.
K
.
I
bns
ouda
,
“
M
e
t
hods
f
or
i
n
vi
t
r
o
e
va
l
ua
t
i
ng
a
nt
i
m
i
c
r
obi
a
l
a
c
t
i
vi
t
y:
a
r
e
vi
e
w
,”
J
our
nal
of
P
har
m
ac
e
ut
i
c
al
A
nal
y
s
i
s
, vol
. 6, no. 2, pp. 71
–
79, A
pr
. 2016, doi
:
10.1016/
j
.j
pha
.2015.11.005.
[
22]
G
. S
.
Z
a
be
u, P
. M
.
C
.
S
c
a
f
f
a
, M
.
C
.
G
i
a
c
om
i
ni
,
C
. d
.
M
.
P
.
V
i
da
l
,
L
. T
j
ä
de
r
ha
n
e
, a
nd L
.
W
a
ng, “
G
e
l
a
t
i
nol
yt
i
c
a
c
t
i
vi
t
y a
f
t
e
r
de
nt
i
n
pr
e
t
r
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a
t
m
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nt
w
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t
h
di
m
e
t
hyl
s
ul
f
oxi
de
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D
M
S
O
)
c
om
bi
ne
d
t
o
de
nt
a
l
bondi
ng
s
ys
t
e
m
s
:
pe
r
s
pe
c
t
i
ve
s
f
or
bi
ol
ogi
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a
l
r
e
s
pons
e
s
,
”
J
our
nal
of
t
he
M
e
c
hani
c
al
B
e
hav
i
or
of
B
i
om
e
di
c
al
M
at
e
r
i
al
s
, vol
. 130, J
un. 2022, doi
:
10.1016/
j
.j
m
bbm
.2022.105188.
[
23]
F
. J
. Á
.
-
M
a
r
t
í
ne
z
, E
.
B
.
-
C
a
t
a
l
á
n
,
M
.
H
.
-
L
ópe
z
,
a
nd
V
.
M
i
c
ol
,
“
A
nt
i
ba
c
t
e
r
i
a
l
p
l
a
n
t
c
o
m
po
un
ds
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e
xt
r
a
c
t
s
a
n
d
e
s
s
e
n
t
i
a
l
o
i
l
s
:
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n
up
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t
e
d
r
e
v
i
e
w
o
n t
he
i
r
e
f
f
e
c
t
s
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n
d p
ut
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t
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ve
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e
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ha
n
i
s
m
s
o
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a
c
t
i
o
n,”
P
hy
t
om
e
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i
n
e
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.
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0,
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1,
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.p
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.
[
24]
M
.
K
.
-
K
a
m
i
ńs
ka
,
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.
K
a
s
z
uba
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.
B
.
-
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i
l
ko
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z
,
M
.
I
c
i
e
k,
M
.
W
r
óbe
l
,
a
nd
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.
K
a
m
i
ńs
ki
,
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D
i
m
e
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hyl
s
ul
f
oxi
de
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M
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s
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nt
i
a
l
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our
c
e
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i
nt
e
r
f
e
r
e
nc
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i
n
r
e
s
e
a
r
c
h
r
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l
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t
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t
o
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ul
f
ur
m
e
t
a
bol
i
s
m
—
a
pr
e
l
i
m
i
na
r
y
s
t
udy
,”
A
nt
i
ox
i
dant
s
,
vol
.
13,
no.
5,
M
a
y 2024, doi
:
10.3390/
a
nt
i
ox13050582.
[
25]
H
.
R
.
N
a
de
e
m
e
t
al
.
,
“
T
oxi
c
i
t
y,
a
nt
i
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c
t
i
vi
t
y,
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nd
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oc
he
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i
c
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l
s
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l
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i
m
um
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i
l
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um
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e
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ve
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c
ul
t
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va
t
e
d
i
n
S
out
he
r
n P
unj
a
b, P
a
ki
s
t
a
n,”
F
oods
, vol
. 11, no. 9, A
pr
. 2022, doi
:
10.3390/
f
ood
s
11091239.
[
26]
L
.
D
.
R
os
s
i
,
G
.
R
o
c
c
he
t
t
i
,
L
.
L
uc
i
ni
,
a
nd
A
.
R
e
be
c
c
hi
,
“
A
nt
i
m
i
c
r
obi
a
l
pot
e
nt
i
a
l
of
pol
yphe
nol
s
:
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e
c
ha
ni
s
m
s
of
a
c
t
i
on
a
nd
m
i
c
r
obi
a
l
r
e
s
pons
e
s
—
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na
r
r
a
t
i
ve
r
e
vi
e
w
,”
A
nt
i
ox
i
dant
s
, vol
. 14, no. 2, F
e
b. 202
5, doi
:
10.3390/
a
nt
i
ox14020200.
[
27]
Y
.
Y
a
n,
X
.
L
i
,
C
.
Z
ha
ng,
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.
L
v,
B
.
G
a
o,
a
nd
M
.
L
i
,
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e
s
e
a
r
c
h
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ogr
e
s
s
on
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nt
i
ba
c
t
e
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l
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c
t
i
vi
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e
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nd
m
e
c
ha
ni
s
m
s
of
na
t
ur
a
l
a
l
ka
l
oi
ds
:
a
r
e
vi
e
w
,”
A
nt
i
bi
ot
i
c
s
, vol
. 10, no. 3, M
a
r
. 2021, doi
:
10.3390/
a
nt
i
bi
ot
i
c
s
10030318.
[
28]
S
.
O
.
O
ye
de
m
i
,
A
.
I
.
O
koh,
L
.
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.
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a
bi
nya
,
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.
P
i
r
oc
he
nva
,
a
nd
A
.
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.
A
f
ol
a
ya
n,
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he
pr
opos
e
d
m
e
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ni
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m
of
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i
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l
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uge
nol
,
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nol
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t
e
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pi
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ne
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ns
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r
e
pt
oc
oc
c
us
py
ge
ne
s
,
P
r
ot
e
us
v
ul
gar
i
s
and
E
s
c
he
r
i
c
hi
a
c
ol
i
,”
A
f
r
i
c
an J
our
nal
of
B
i
ot
e
c
hnol
ogy
, vol
. 8, no. 7, pp. 1280
–
1286, 2009.
[
29]
B
.
K
.
-
K
r
oc
hm
a
l
a
nd
R
.
D
.
-
W
i
c
he
r
,
“
T
he
m
i
ni
m
um
i
nhi
bi
t
or
y
c
onc
e
nt
r
a
t
i
on
of
a
nt
i
bi
ot
i
c
s
:
m
e
t
hods
,
i
nt
e
r
pr
e
t
a
t
i
on,
c
l
i
n
i
c
a
l
r
e
l
e
va
nc
e
,”
P
at
hoge
ns
, vol
. 10, no. 2, F
e
b. 2021, doi
:
10.3390/
pa
t
hoge
ns
10020
165.
[
30]
W
.
M
ą
c
z
ka
,
A
.
D
.
-
M
a
de
j
,
M
.
G
r
a
ba
r
c
z
yk,
a
nd
K
.
W
i
ńs
ka
,
“
N
a
t
ur
a
l
c
om
pounds
i
n
t
he
ba
t
t
l
e
a
ga
i
ns
t
m
i
c
r
oo
r
ga
ni
s
m
s
—
l
i
na
l
ool
,”
M
ol
e
c
ul
e
s
, vol
. 27, no. 20, O
c
t
. 2022, doi
:
10.3390/
m
ol
e
c
ul
e
s
27206928.
[
31]
P
.
A
nge
l
i
ni
,
“
P
l
a
nt
-
de
r
i
ve
d
a
nt
i
m
i
c
r
obi
a
l
s
a
nd
t
he
i
r
c
r
uc
i
a
l
r
ol
e
i
n
c
om
ba
t
i
ng
a
nt
i
m
i
c
r
obi
a
l
r
e
s
i
s
t
a
nc
e
,”
A
nt
i
bi
ot
i
c
s
,
vol
.
13,
no.
8,
A
ug. 2024, doi
:
10.3390/
a
nt
i
bi
ot
i
c
s
13080746.
[
32]
S
.
N
C
a
nd
D
.
M
a
noha
r
a
n,
“
S
t
udy
on
e
uge
nol
a
s
a
pot
e
nt
i
a
l
a
nt
i
ba
c
t
e
r
i
a
l
a
ge
nt
a
ga
i
ns
t
:
St
r
e
pt
oc
oc
c
u
s
m
ut
ans
and
E
s
c
he
r
i
c
hi
a
c
ol
i
,”
E
P
R
A
I
nt
e
r
nat
i
onal
J
our
nal
of
R
e
s
e
ar
c
h
&
D
e
v
e
l
opm
e
nt
, vol
. 9, no. 12, pp. 138
–
145, D
e
c
. 2024, doi
:
10.36713/
e
pr
a
19405.
[
33]
S
.
D
a
hha
m
e
t
al
.
,
“
T
he
a
nt
i
c
a
nc
e
r
,
a
nt
i
oxi
da
nt
a
nd
a
nt
i
m
i
c
r
obi
a
l
pr
ope
r
t
i
e
s
of
t
he
s
e
s
qui
t
e
r
pe
ne
β
-
c
a
r
yophyl
l
e
ne
f
r
om
t
he
e
s
s
e
nt
i
a
l
oi
l
of
A
qui
l
a
r
i
a
c
r
a
s
s
n
a
,
”
M
ol
e
c
ul
e
s
, vol
. 20, no. 7, pp. 11808
–
11829,
J
un. 2015, doi
:
10.3390/
m
ol
e
c
ul
e
s
200711808.
[
34]
A
.
M
.
M
uha
m
m
e
d,
R
.
M
.
S
ubbu,
L
.
J
i
r
ove
t
z
,
a
nd
S
.
P
.
M
oha
m
e
d,
“
C
om
pos
i
t
i
on
a
nd
a
nt
i
m
i
c
r
obi
a
l
a
na
l
ys
i
s
of
t
he
e
s
s
e
nt
i
a
l
oi
l
of
L
i
t
s
e
a
L
a
e
vi
ga
t
a
N
ees
.
(
L
aur
ac
e
ae
)
,”
N
at
ur
al
P
r
oduc
t
C
om
m
uni
c
at
i
ons
, vol
. 3,
no. 7, 2008, doi
:
10.1177/
1934578X
0800300707.
[
35]
M
. Z
a
m
pi
ni
, D
. S
a
na
br
i
a
, N
. P
hi
l
l
i
ps
, a
nd C
. S
pe
nc
e
, “
T
he
m
ul
t
i
s
e
n
s
or
y pe
r
c
e
p
t
i
on of
f
l
a
vor
:
a
s
s
e
s
s
i
ng
t
he
i
nf
l
ue
nc
e
of
c
ol
or
c
ue
s
on
f
l
a
vor
di
s
c
r
i
m
i
na
t
i
on
r
e
s
pons
e
s
,”
F
ood
Q
ual
i
t
y
and
P
r
e
f
e
r
e
nc
e
,
vol
.
18,
no.
7,
pp.
975
–
984,
O
c
t
.
2007,
doi
:
10.1016/
j
.f
oodqua
l
.2007.04.001.
[
36]
B
.
O
z
e
l
,
S
.
K
uz
u,
M
.
A
.
M
a
r
a
ngoz
,
S
.
D
ogdu,
R
.
H
.
M
or
r
i
s
,
a
nd
M
.
H
.
O
z
t
op,
“
H
a
r
d
c
a
ndy
pr
oduc
t
i
on
a
nd
qua
l
i
t
y
pa
r
a
m
e
t
e
r
s
:
a
r
e
vi
e
w
,”
O
pe
n R
e
s
e
ar
c
h E
ur
ope
, vol
. 4, M
a
r
. 2024, doi
:
10.12688/
ope
nr
e
s
e
ur
o
pe
.16792.1.
[
37]
Á
.
C
.
-
S
á
nc
he
z
,
K
.
L
e
c
h,
A
.
S
z
um
ny,
A
.
F
i
gi
e
l
,
a
nd
Á
.
A
.
C
.
-
B
a
r
r
a
c
hi
na
,
“
V
ol
a
t
i
l
e
c
om
pos
i
t
i
on
of
s
w
e
e
t
ba
s
i
l
e
s
s
e
nt
i
a
l
oi
l
(
O
c
i
m
um
bas
i
l
i
c
um
L.
)
a
s
a
f
f
e
c
t
e
d
by
dr
yi
ng
m
e
t
hod,”
F
ood
R
e
s
e
ar
c
h
I
nt
e
r
nat
i
onal
,
vol
.
48,
no.
1,
pp.
217
–
225,
A
ug.
2012,
doi
:
10.1016/
j
.f
oodr
e
s
.2012.03.015.
[
38]
E
.
S
ve
c
ova
a
nd
J
.
N
e
uge
ba
ue
r
ová
,
“
A
s
t
udy
of
34
c
ul
t
i
va
r
s
of
ba
s
i
l
(
O
c
i
m
um
L
.)
a
nd
t
he
i
r
m
or
phol
ogi
c
a
l
,
e
c
onom
i
c
a
nd
bi
oc
he
m
i
c
a
l
c
ha
r
a
c
t
e
r
i
s
t
i
c
s
,
u
s
i
ng
s
t
a
nda
r
di
z
e
d
d
e
s
c
r
i
pt
or
s
,”
A
c
t
a
U
ni
v
e
r
s
i
t
a
t
i
s
Sapi
e
nt
i
ae
:
A
l
i
m
e
nt
ar
i
a
,
vol
.
3,
pp.
118
–
125,
2010.
[
39]
L
.
J
i
r
ove
t
z
,
G
.
B
uc
hba
ue
r
,
M
.
P
.
S
ha
f
i
,
a
nd
M
.
M
.
K
a
ni
a
m
pa
dy,
“
C
h
e
m
ot
a
xonom
i
c
a
l
a
na
l
ys
i
s
of
t
he
e
s
s
e
nt
i
a
l
oi
l
a
r
om
a
c
om
pounds
of
f
our
di
f
f
e
r
e
nt
O
c
i
m
um
s
p
e
c
i
e
s
f
r
om
S
out
he
r
n
I
ndi
a
,”
E
ur
ope
a
n
F
ood
R
e
s
e
ar
c
h
and
T
e
c
hnol
ogy
,
vol
.
217,
no.
2
,
pp. 120
–
124, A
ug. 2003, doi
:
10.1007/
s
00217
-
003
-
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40.
H
um
ul
e
ne
30.063
67418248
6.81
95
41.
N
a
pht
ha
l
e
ne
, 1,2,3,5,6,8a
-
he
xa
hydr
o
-
4,7
-
di
m
e
t
hyl
-
1
-
(1
-
m
e
t
hyl
e
t
hyl
)
-
, (
1S
-
c
i
s
)
-
33.054
48693666
1.80
91
42.
N
a
pht
ha
l
e
ne
, 1,2,3,4,4a
,5,6,8a
-
oc
t
a
hydr
o
-
7
-
m
e
t
hyl
-
4
-
m
e
t
hyl
e
ne
-
1
-
(1
-
m
e
t
hyl
e
t
hyl
)
(
1α
,4a
.be
t
a
.,8α
)
-
31.069
7932945
1.30
92
43.
α
-
G
ua
i
e
ne
31.555
12421407
0.21
91
44.
β
-
B
i
s
a
bol
e
ne
32.432
46144169
0.33
95
45.
C
opa
e
ne
33.386
100459727
1.23
95
O
xyge
na
t
e
d s
e
s
qui
t
e
r
pe
ne
s
46.
C
a
r
yophyl
l
a
-
4(
12)
,8(
13
)
-
di
e
n
-
5 α
-
ol
37.617
7144854
2.68
85
E
uge
nol
47.
2,6
-
O
c
t
a
di
e
n
-
1
-
ol
, 3,7
-
di
m
e
t
hyl
-
, f
or
m
a
t
e
, (
Z
)
-
23.382
20621083
0.19
95
48.
2,6
-
O
c
t
a
di
e
n
-
1
-
ol
, 3,7
-
di
m
e
t
hyl
-
, a
c
e
t
a
t
e
, (
Z
)
-
26.25
76053738
0.55
96
O
t
he
r
C
om
pounds
49.
C
yc
l
ohe
xa
ne
, 1
-
e
t
he
nyl
-
1
-
m
e
t
hyl
-
2,4
-
bi
s
(
1
-
m
e
t
hyl
e
t
he
nyl
)
-
, [
1S
-
(1
α
,2
β
,4
β
)]
-
27.378
30781991
2.03
95
50.
B
i
c
yc
l
o[
7.2.0]
unde
c
-
4
-
e
ne
, 4,11,11
-
t
r
i
m
e
t
hyl
-
8
-
m
e
t
hyl
e
ne
-
28.01
9206469
0.82
95
51.
10,10
-
D
i
m
e
t
hyl
-
2,6
-
di
m
e
t
hyl
e
ne
bi
c
yc
l
o[
7.2.0]
unde
c
a
ne
28.941
11112436
0.25
94
52.
(
E
)
-
β
-
F
a
m
e
s
e
ne
30.236
8637055
0.30
92
53.
B
i
c
yc
l
o[
7.2.0]
unde
c
-
4
-
e
ne
, 4,11,11
-
t
r
i
m
e
t
hyl
-
m
e
t
hyl
e
ne
-
,[
1R
-
(
1R
*,4Z
,9S
*)
]
-
31.423
51631003
0.23
92
54.
P
e
nt
a
de
c
a
ne
32.011
67260267
1.38
96
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