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Rowachol: A possible treatment for cholesterol gallstones

Authors:

Abstract

It has been claimed that Rowachol, a proprietary choleretic, is occasionally successful in the treatment of gallstones. In gallstone patients we have examined its effect on the lipid composition of (1) samples of fasting gall bladder bile obtained at the time of cholecystectomy, and (2) T-tube bile on the tenth post-operative day. In a dose of two capsules, three times a day for only 48 hours, Rowachol significantly lowered the cholesterol solubility of both gall bladder (P less than 0.001) and T-tube bile (P less than 0.05). Rowachol in a dose of one capsule three times a day for 48 hours did not alter bile composition, while four capsules four times a day for a similar period caused a significant (P less than 0.05) deterioration in biliary lipid composition. The possible mechanisms of action of Rowachol and their therapeutic implications are discussed.
Gut,
1979,
20,
312-317
Clinical
trial
Rowachol
-
a
possible
treatment
for
cholesterol
gallstones'
J.
DORAN,
M.
R.
B.
KEIGHLEY,
AND
G.
D.
BELL
From
the
University
Department
of
Therapeutics,
City
Hospital,
Nottingham,
and
the
University
Department
of
Surgery,
General
Hospital,
Birmingham
SUMMARY
It
has
been
claimed
that
Rowachol,
a
proprietary
choleretic,
is
occasionally
successful
in
the
treatment
of
gallstones.
In
gallstone
patients
we
have
examined
its
effect
on
the
lipid
composi-
tion
of
(1)
samples
of
fasting
gall
bladder
bile
obtained
at
the
time
of
cholecystectomy,
and
(2)
T-tube
bile
on
the
tenth
post-operative
day.
In
a
dose
of
two
capsules,
three
times
a
day
for
only
48
hours,
Rowachol
significantly
lowered
the
cholesterol
solubility
of
both
gall
bladder
(p
<
0001)
and
T-tube
bile
(p
<
005).
Rowachol
in
a
dose
of
one
capsule
three
times
a
day
for
48
hours
did
not
alter
bile
composition,
while
four
capsules
four
times
a
day
for
a
similar
period
caused
a
significant
(p
<
0-05)
deterioration
in
biliary
lipid
composition.
The
possible
mechanisms
of
action
of
Rowachol
and
their
therapeutic
implications
are
discussed.
The
bile
of
patients
with
cholesterol
gallstones
is
frequently
saturated
with
cholesterol
(Admirand
and
Small,
1968).
It
has
been
shown
that
chenodeoxy-
cholic
acid
(CDCA)
enhances
the
cholesterol
solubility
of
human
bile
and
in
suitable
patients
promotes
dissolution
of
cholesterol
gallstones
(Bell
et
al.,
1972;
Danzinger
et
al.,
1972;
Thistle
and
Hofmann,
1973;
Iser
et
al.,
1975;
Thistle
et
al.,
1978).
One
of
the
major
disadvantages
of
CDCA
therapy
is
the
fact
that
the
patient
with
large
gallstones
(greater
than
1
cm
in
diameter)
may
need
to
take
the
drug
for
several
years
before
successful
dissolution
is
observed
radiologically
(Dowling,
1977).
Several
possible
adjuncts
to
CDCA
therapy
have
been
suggested
including
phenobarbitone
(Coyne
et
al.,
1975),
P
sitosterol
(Gerolami
and
Sarles,
1975;
Maudgal
et
al.,
1977;
Begemann
et
al.,
1978;
Thistle
et
al.,
1978),
choline
(Thistle
et
al.,
1978),
and
a
low
cholesterol
diet
(Maudgal
et
al.,
1977).
None
of
these
'adjuvants'
has
yet
been
shown
actually
to
accelerate
the
speed
of
gallstone
dissol-
ution
(Thistle
et
al.,
1978)
and
so
the
search
for
safe
and
effective
alternatives
and/or
adjuvants
to
CDCA
continues.
Rowachol2
is
a
proprietary
choleretic
consisting
of
six
cyclic
monoterpenes
(Fig.
1),
all
derived
from
'Presented
in
part
at
the
York
Meeting
of
the
British
Society
of
Gastroenterology,
September
1977
(Gut
(1977)
18,
A.977).
'Rowa
Ltd,
Bantry,
Co.
Cork,
Eire.
Received
for
publication
2
November
1978
purified
plant
essential
oils-for
example,
1-menthol
from
Mentha
piperidis,
the
peppermint
plant
or
1-cineol
from
eucalyptus
leaves.
This
particular
combination
of
terpenes
was
chosen
by
the
manu-
facturer
because,
in
the
rat,
it
was
shown
to
have
a
larger
and
more
sustained
choleretic
effect
than
equimolar
quantities
of
any
of
its
individual
con-
stituents
(Morsdorf,
1966).
This
agent
has
been
extensively
marketed
in
Europe
for
over
25
years,
and
is
freely
available
on
prescription
in
the
United
Kingdom.
There
have
been
a
number
of
papers
in
the
German
(Blumenberg,
1957),
Japanese
(Kameda,
1960;
Okabe,
1960;
Noda
et
al.,
1965),
and
English
(Hordinsky,
1971,
1973)
literature
reporting
that
prolonged
courses
of
Rowachol
treatment
have
resulted
in
successful
dissolution
of
patients'
gallstones.
In
the
above
papers
the
only
reported
side-effect
was
of
a
peppermint
or
camphor
taste
after
eructation.
Since
this
preparation
seemed,
therefore,
to
be
substantially
free
from
side-effects,
we
felt
that
any
claims
of
efficacy
deserved
careful
consideration.
Several
of
the
terpenes
in
Rowachol-
for
example,
menthol,
menthone,
pinene-have
long
been
shown
to
be
excellent
cholesterol
solvents
in
vitro,
and
indeed
the
structurally
related
terpene,
d-limonene,
has
recently
been
advocated
as
an
agent
for
dissolving
retained
common
duct
stones
(Igimi
et
al.,
1976).
However,
it
is
unlikely
that
significant
amounts
of
these
compounds
appear
in
bile
because
of
their
relatively
low
molecular
weight
(Smith,
1973).
Previous
studies
in
the
rat
(Morsdorf
and
Wolf,
1966;
Kodama
et
al.,
1976)
and
dog
(Kodama
312
Rowachol-a
possible
treatment
for
cholesterol
gallstones
CH3
CH
CI
*rC
PINlE
BORNEOL
CH3
C
CH
H2C
CM2
H2C
C<
CH,
H2C
CH2
MCC.
CH2
CH
H3
C
CM3
CINEOL
Fig.
1
Chemical
formulae
of
terpenes
in
Rowachol-
menthol
32%,
menthone
6%,
pinene
17%,
borneol
5%,
cineol
2
%,
camphene
5
%,
made
up
to
100
%
with
olive
oil.
Each
capsule
contains
01
ml
of
liquid.
et
al.,
1976)
have
shown
that
a
number
of
cyclical
monoterpenes
and
their
metabolites
can
affect
bile
flow
and
biliary
lipid
composition.
We
argued
that
any
cholelitholytic
effect
that
Rowachol
might
have
in
man
was
also
likely
to
be
mediated
by
induced
alterations
in
the
lipid
composition
of
bile.
We
therefore
studied
the
effect
of
orally
administered
Rowachol
on
bile
salt,
phospholipids,
and
choles-
terol
output
in
T-tube
bile
and
the
resultant
changes
in
the
cholesterol
solubilising
capacity
of
gall
bladder
bile.
Methods
EFFECT
OF
ROWACHOL
ON
BILIARY
LIPID
SECRETION
Nineteen
patients
were
studied.
All
had
undergone
cholecystectomy
and
exploration
of
the
common
bile
duct
for
gallstones
with
insertion
of
a
T-tube.
Between
the
sixth
and
eighth
postoperative
days
a
T-tube
cholangiogram
was
performed
and
found
to
be
normal
before
the
T-tube
was
clamped
to
restore
the
enterohepatic
circulation
of
bile
salts.
Eight
patients
(age
51P4
years
±
SEM
4
9;
range
22-66
years;
weighing
61-3
kg
±
2-0,
range
53-70
kg)
then
received
Rowachol
by
mouth
at
a
dose
of
two
capsules
tds
(each
capsule
contains
32
mg
menthol,
17
mg
pinene,
6
mg
menthone,
5
mg
each
of
borneol
and
camphene
and
2
mg
cineole).
The
other
11
patients
(age
501
years
±
5
5,
range
25-70
years;
weight
61-0
kg
±
2-5,
range
46-71
kg)
acted
as
controls.
In
all
cases
the
patients'
gallstones
appeared
to
be
of
predominantly
cholesterol
type,
but
chemical
analysis
was
not
performed.
After
48
hours
the
T-tube
was
unclamped
and
bile
collected
by
gravity
drainage.
Bile
was
collected
into
graduated
tubes
at
10-minute
intervals
for
140
minutes,
bile
flow
was
recorded
and
the
samples
were
stored
at
-
20°C
for
later
analysis
of
biliary
lipid
content.
We
decided
to
collect
bile
for
a
total
of
140
minutes
in
the
present
study
so
that
we
could
compare
the
results
obtained
with
those
previously
reported
when
ioglycamide
was
infused
intravenously
for
120
minutes
after
a
20
minute
baseline
period
of
observation
(Bell
et
al.,
1
978a).
EFFECT
OF
ROWACHOL
ON
GALL
BLADDER
BILE
COMPOSITION
Forty-nine
patients
undergoing
elective
cholecystec-
tomy
were
studied.
All
had
radiolucent
stones
in
functioning
gall
bladders.
Twenty
received
no
medi-
cation
before
surgery
and
acted
as
controls,
while
the
other
29
were
given
Rowachol
for
48
hours
before
operation.
Three
different
doses
of
Rowachol
were
used---one
capsule
tds
(nine
patients);
two
capsules
tds
(12
patients);
and
four
capsules
qds
(eight
patients).
The
groups
were
not
formally
matched,
but
were
comparable
for
age,
weight,
and
sex
distribution.
Gall
bladder
bile
was
obtained
by
needle
aspiration
at
the
time
of
operation.
ANALYSIS
OF
BILE
SAMPLES
Biliary
bile
acid
concentration
was
measured
enzymatically
using
3ohydroxysteroid
dehydro-
genase
(Talalay,
1960).
Phospholipids
were
deter-
mined
using
the
method
of
Bartlett
(1959),
while
cholesterol
was
assayed
using
a
modification
of
the
method
of
Carr
and
Drekter
(1956)
after
lipid
313
314
extraction
with
chloroform:methanol
(2:1
V/V).
The
cholesterol
saturation
index
(CSI)
was
cal-
culated
using
the
equation
devised
by
Thomas
and
Hofmann
(1973)
based
on
the
limits
of
cholesterol
solubility
as
defined
by
Hegardt
and
Dam
(1971).
STATISTICAL
ANALYSIS
The
statistical
significance
of
differences
between
the
results
was
assessed
using
Student's
unpaired
t
test.
Results
EFFECT
OF
ROWACHOL
ON
BILIARY
LIPID
SECRETION
Rowachol
in
a
dose
of
two
capsules
tds
for
48
hours
did
not
influence
bile
flow
(Table).
The
rates
of
secretion
of
bile
salts.
phospholipids,
and
choles-
terol
in
the
T-tube
patients
on
and
off
Rowachol
is
shown
in
the
Table.
Numerically,
bile
salt
and
phos-
pholipid
secretion
were
enhanced,
while
cholesterol
2.0
X
4)
-0
c
c
0
15
:3
z
C.
1.5
1.0
0.5
J.
Doran,
M.
R.
B.
Keighley,
and
G.
D.
Bell
output
was
slightly
depressed,
but
the
difference
between
the
treated
and
control
groups
was
not
statistically
significant.
The
mean
cholesterol
saturation
index
of
T-tube
bile
in
the
two
groups
is
plotted
graphically
in
Fig.
2.
During
the
first
hour
of
collection
the
bile
from
the
treated
patients
was
significantly
less
saturated
with
cholesterol
than
was
the
bile
from
the
controls.
After
60
minutes
the
bile
from
both
groups
began
to
be
more
saturated,
as
the
bile
salt
pool
was
being
depleted,
and
the
differences
between
the
groups
were
no
longer
as
marked.
EFFECT
OF
ROWACHOL
ON
COMPOSIT1ON
OF
GALL
BLADDER
BILE
Figure
3
shows
that
the
effect
of
Rowachol
on
the
composition
of
gall
bladder
bile
varies
with
the
dose
given.
The
mean
cholesterol
saturation
index
SEM)
for
the
controls
was
1V313
±
0080
and
for
patients
receiving
the
lowest
dose
of
Rowachol
was
1-426
±
0-105
(p
=
NS).
However,
in
patients
--
Rowachol
(n-8)
-A
Controls
(n-li)
.40
1-
A
.-
-
.
I..
*
-
-t
'o,
-.,
1,4Z
.1
...
..
Fig.
2
Effect
of
Rowachol
on
the
cholesterol
saturation
index
of
T-tube
bile
during
140
minutes'
drainage.
|)
<
O.
05
I
I
I
I
20
40
60
X0
1(X)
120
140
Timne
(miniutes)
Table
Bile
flow
(ml/min)
and
biliary
excretion
of
bile
salts,
phospholipids,
and
cholesterol
(pmol!min
±
SEM)
in
control
patients
and
those
receiving
Rowachol
Time
(min)
Controls
(n
=
11)
Rowachol
(n
=
8)
Bile
flow
BS
PL
Ch
Bile
flow
BS
PL
Ch
0-
10
0-81
±009
24-7 4-4
93
+
1-4
2-7
+
04
081
+
006
34-5
±
5-0
108
±
-5
2-5
±
02
10-
20
0-72
i
0-08
22-2
4
0
7
9
+
1
1
2-6
±
04
0
73
+
0
09
31-9
±
3
0
9
9
i
10
2-3
0
3
20-
30
0-76±
007
24-1+
49
8-6
+
13
2-7
±03
0-75
+
0-08
33-5
+5-6
101
±07
2-3
±02
30-
40
0-87±
009
286
+5-4
100
1-4
3-1
±04
079
+
009
38-0±
69
108
+
07
2-4
+02
40-
50
0-78+
007
27-0
5-1
8-9
1-3
2-7
+03
079
+
0-09
38-7
+7-3
115
+09
26
±03
50-
60
0-81+
007
28-0
+5-7
8-8
±11
2-8+
03
0-84+
009
37-6
8-9
11-3
4
09
25
±0-2
60-
70
0-86
+
0-06
28-4
+
5-3
9
0
+
0
9
2-7
0
3
0
79
+
010
33
9
±
91
10
0
0-8
2-5
+
0-2
70-
80
0-78
0-08
28-4
4
57
8-7
1+1
2-4
4
03
0-78+
010
32-6
8-9
105
±11
2-4
0-2
80-
90
0-78
t009
272
+
5-5
8-7
+10
2-5
0-2
0-76
0-12
327
+79
10-6
1-2
2-4
t03
90-100
0-67
+007
22-2
±
5.5
7-4
1±0
2-2
+0-2
074+
007
30-3
49
10-3+
09
24
±0-2
100-110
0-67
0-08
24-8
±
4-5
7-1
i
10
2-4
+
03
0-66
i
007
26-8
±
59
9-5
1
P2
2
1
±
03
110-120
0-58
0-05
18-7
4-
42
6-4
10
2-2
0-2
0-57
+
007
18-8
2-8
80
i
09
1-8
0-2
120-130
0-58
±
007
15-4
±
4
0
5
6
i
0-8
2-1
i
02
0
52
+
005
13
9
1-4
7-1
+
0
7
1
8
i
0.1
130-140
0-62+
012
123
+
30
5-5
±1+0
2-1+
03
0-56±
004
14-1±
25
76
±10
21
±02
Rowachol-a
possible
treatment
for
cholesterol
gallstones
3.0k
2.
5
2.0k
1.5
1.0
p
-.-
.3
a
s
*I
N.S.
p<0.001
p<0.05
Il
I
I
2
caps
4
caps
t.d.s.
q.d.s.
0.5
Controls
1
cap
t.
d.
s.
Fig.
3
Cholesterol
saturation
index
of
gall
bladder
bile
from
controls
and
from
patients
given
Rowachol
for
48
hours
before
surgery.
receiving
a
dose
of
two
capsules
tds
the
cholesterol
saturation
index
was
0
900
+
0-51,
which
is
signi-
ficantly
lower
than
the
controls
(p
<
0-001).
Nine
of
the
12
patients
in
this
group
had
bile
that
was
less
than
saturated
with
cholesterol.
In
contrast,
the
cholesterol
saturation
index
of
1-743
+
0262
found
in
the
patients
given
the
largest
dose
was
significantly
higher
than
that
of
the
controls
(P
<
0-05).
Discussion
The
results
of
this
study
show
that
Rowachol,
in
a
dose
of
two
capsules
three
times
a
day
for
48
hours,
significantly
enhances
the
cholesterol
solubility
of
human
T-tube
and
gall
bladder
bile.
In
most
pre-
vious
series,
gallstone
patients
treated
with
Rowachol
(Blumenberg,
1957;
Kameda,
1960;
Okabe,
1960;
Noda
et
al.,
1955;
Hordinsky,
1971,
1973)
received
the
preparation
in
liquid
form
in
daily
doses
equivalent
to
only
two
to
four
of
the
enteric-coated
capsules
employed
in
the
present
study.
It
can
be
seen
from
our
own
study
that
one
capsule
of
Rowachol
three
times
a
day
for
48
hours
failed
to
alter
bile
composition.
It
is
possible
there-
fore
that
the
low
gallstone
dissolution
rates
reported
in
some
series
(Hordinsky,
1971)
may
simply
reflect
the
fact
that
the
dose
employed
was
too
small.
D-limonene
(p-mentha-1,8-diene)
occurs
as
a
major
component
of
the
essential
oils
of
citrus
fruits.
It
is
a
monoterpene
structurally
similar
to
several
of
the
terpenes
in
Rowachol.
Kodama
et
al.
(1976)
have
recently
shown
that
in
the
rat
d-limonene
decreased
the
ratio
of
biliary
bile
salts
and
phospholipids
to
cholesterol,
while,
on
the
other
hand,
one
of
its
major
metabolites,
p-menth-l-
ene-8,9-diol,
significantly
increased
the
same
ratio.
It
is
possible
that
some
of
the
terpenes
in
Rowachol
(or
their
metabolites)
favourably
influence
biliary
lipid
composition,
while
others,
like
d-limonene
itself,
cause
a
deterioration.
This
could
possibly
explain
why
the
largest
dose
of
Rowachol
(four
capsules
qds)
caused
an
increase
in
the
cholesterol
saturation
of
bile,
while
the
lower
dose
decreased
it.
Measurement
of
the
rate
limiting
enzymes
of
hepatic
cholesterol
(HMGCoA
Reductase)
and
bile
acid
synthesis
(cholesterol
70xhydroxylase)
in
the
microsomal
fraction
of
liver
from
patients
with
cholesterol
gallstones
has
shown
increased
HMGCoA
reductase
activity
and
diminished
7othydroxylase
activity
(Nicolau
et
al.,
1974a,
1974b;
Salen
et
al.,
1975).
It
has
recently
been
shown
that
cholesterol
secretion
into
bile
is
correlated
with
HMGCoA
reductase
levels
in
the
liver
(Key
et
al.,
1977).
CDCA
and
the
structurally
related
bile
acid
urso-
deoxycholic
acid
enhance
the
cholesterol
solubility
of
human
bile
and
promote
cholesterol
gallstone
dissolution
by
depressing
hepatic
HMGCoA
re-
ductase
(Coyne
et
al.,
1976;
Maton
et
al.,
1977).
In,
our
T-tube
patients
Rowachol
increased
bille
salt
and
slightly
decreased
cholesterol
output.
Similar
findings
have
previously
been
reported
in
the
rat
(Morsdorf
and
Wolf,
1966).
We
have
shown
that
this
terpene
preparation
significantly
depressed
hepatic
HMGCoA
reductase
levels
in
the
rat
(Bell
et
al.,
1
978b).
We
are
currently
investigating
all
the
individual
terpene
constituents
of
Rowachol
to,
determine,
in
the
rat,
how
much
each
one
contri-
butes
to
this
effect.
Having
determined
the
'active'
ingredient(s)
of
this
terpene
preparation
in
the
rat,
we
then
intend
to
carry
out
a
formal
dose
response
study
in
man.
Despite
its
complex
composition
we
chose
to
use
Rowachol
in
the
present
pilot
study
because
it
was
(1)
readily
available
in
the
United
Kingdom;
(2)
known
to
be
safe
when
given
for
prolonged
periods,
and
(3)
had
previously
been
shown
occasionally
to
dissolve
patients'
gallstones
(Blumenberg,
1957;
Kameda,
1960;
Okabe,
1960;
Noda
et
al.,
1965;
Hordinsky,
1971,
1973).
We
ourselves
have
now
treated
27
patients
with
radiolucent
gallstones
for
x
a)
c
0
-
a)
L.0
0)
u
C)
C-
315
3.5r-
0
.L
i
00
r
6
*
a
316
J.
Doran,
M.
R.
B.
Keighley,
and
G.
D.
Bell
periods
of
six
to
12
months.
We
already
have
radiological
evidence
of
gallstone
dissolution/
disappearance
in
seven
of
the
patients
taking
the
terpene
preparation.
The
drug
was
well
tolerated
by
the
patients
and
no
evidence
of
hepatotoxicity
emerged
(Bell
et
al.,
1978b).
It
is
known
that
certain
terpenes
such
as
cineol
(eucalyptol)
and
of
pinene
are
potent
hepatic
micro-
somal
enzyme
inducers
(Jori
et
al.,
1972).
It
is
perhaps
not
surprising
therefore
to
find
that
Rowa-
chol
itself
significantly
(p
<
0O01)
increased
urinary
D-glucaric
acid
excretion
when
given
to
patients
in
a
dose
of
two
capsules
tds
for
six
weeks
(Bell
et
al.,
1978c).
We
are
currently
investigating
the
effect
of
this
terpene
preparation
on
a
series
of
hepatic
microsomal
enzymes
including
cholesterol
7cx-
hydroxylase,
as
at
the
present
time
we
have
no
good
explanation
for
the
increased
bile
salt
secretion
observed
either
in
our
own
study
or
the
previous
one
of
Morsdorf
and
Wolf
(1966).
Previous
studies
in
the
rat
(Traissac
et
al.,
1963;
M6rsdorf,
1966;
M6rsdorf
and
Wolf,
1966)
and
in
man
(Traissac,
et
al.,
1963;
Hordinsky,
1973)
have
shown
Rowachol
to
be
a
potent
choleretic.
M6rsdorf
(1966)
showed
that
menthol
and
borneol
were
the
most
potent
choleretics
in
Rowachol.
The
choleresis
produced
by
these
terpenes
and
also
others
such
as
d-limonene
(Kodama
et
al.,
1976)
is
dose-related.
In
the
present
study
no
obvious
choleretic
effect
was
noted.
This
may
be
because
(1)
the
last
dose
was
at
least
12
hours
before
the
start
of
the
experiment,
and
(2)
the
dose
used
(in
mg/kg
body
weight)
was
relatively
small.
We
conclude
that
the
terpene
preparation,
Rowachol,
its
individual
constituents,
and
possibly
other
related
compounds
merit
further
investigation
as
possible
cholelitholytic
agents.
The
authors
are
grateful
to
Rowa
Ltd,
who
kindly
supplied
the
Rowachol
capsules,
and
also
had
English
translations
made
of
the
papers
quoted
from
the
Japanese
literature;
One
of
us
(J.D.)
was
in
receipt
of
a
grant
from
Schering
Chemicals
Ltd.
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a
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American
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G.
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of
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re-
sponse
to
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England
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... May be late, through the development of inflammatory scars involving Oddi's sphincter or bile duct, recurrent stones or biliary dyskinesia (Girometti et al. 2010). Rowachol, a cyclic monoterpenes-based preparation has been marketed to treat biliary stone disease (Doran et al. 1979). Oral treatment with bile acids results to a cholesterol desaturation by decreasing its biliary secretion, resulting in a progressive dissolution of cholesterol within the gallstones. ...
Article
We studied the gallstone dissolving capacity of Moroccan citrus (C) essential oils; C. clementina, C. aurantium, C. sinensis and C. paradisi. Their litholytic activity was compared to that of their main constituents revealed by a gas chromatography-mass spectrometry (GC–MS) analysis; limonene, linalool and γ-terpinene and to the Methyl tertbutyl ether (MTBE) standard as well. Gallstone sample was classified as a cholesterol type after a quantification analysis, using UV-spectrophotometer. The hydrocarbon compounds predominated the chemical composition of the oils, limonene was the commonly major identified compound, representing between 72.06 and 88.49 %. The citrus essential oils caused a deterioration in the morphological appearance of gallstone samples. The C. sinensis essential oil manifested with remarkable litholytic activity after a day of incubation, reached to a dissolution capacity of 95.78 ± 0.49 %, the same for C. clementina with 94.81 ± 1.30 % and C. aurantium with 92.99 ± 2.04 %. These oils were more effective than MTBE standard. In last position, C. paradisi essential oil exhibited the less high dissolution of 87.68 ± 1.82 %, comparing with other oils. Linalool showed a good litholytic activity, better than that of MTBE and similar to that of limonene. Therefore, in addition to limonene role, also the other constituents may have, as a natural mixture, an important additive effect in the gallstone dissolution of each essential oil.
... 171 In respect of this, peppermint essential oil, not only stimulates bile fluid secretion but may be involved in upregulating the bile acid synthesis-related gene, cholesterol 7α-hydroxylase (CYP7A1), and the nuclear bile acid receptor FXR (farnesoid X receptor) mRNA. 172 It has been shown that the terpene preparation Rowachol, which contains menthol and menthone, 173 has cholelitholytic activity and its use has been recommended with careful monitoring for potential complications during cholesterol gallstone treatment. 174 A mechanism underlying Rowachol activity may derive from a combination of its cholelitholytic, choleretic and spasmolytic properties which would tend to facilitate the passage of common bile duct gallstones. ...
Article
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Peppermint (Mentha x piperita L.) is not only used as a medicinal plant with therapeutic activity but also as a tea infusion, herb, spice or as a flavoring agent in other preparations. However, its adverse side effects on health have been described. The outcome of this review revealed that peppermint and its main constituents (pulegone, menthone, menthol and menthofuran) are moderately toxic. Peppermint and its menthol isomers possess no major innate mutagenic, genotoxic or embryotoxic properties. Peppermint essential oil interacts with cytochrome P450 isoenzymes in human liver microsomes. It is contraindicated in patients with bile duct obstruction and gall bladder inflammation. In patients with gastrointestinal reflux or hiatus hernia, its use should be exercised with caution because it may exacerbate the symptoms of gastrointestinal reflux.
Chapter
Many genetic and environmental factors are involved in the pathogenesisPathogenesis of the formation of gallbladder (GB) stones. GB stone is divided into cholesterol gallstoneGallstones, black pigment stone, and brown pigment stone. Each stone has different pathogenesis. TreatmentTreatment of GB stone is divided into surgical and medical treatment according to the presence of biliary colic. Laparoscopic cholecystectomyLaparoscopic cholecystectomy is standard in symptomatic GB stone patients with definite biliary colic. However, medical treatment may be helpful in patients without surgical indication. The treatment of gallstone in pregnant patients is the same as general gallstone treatment, but it is essential to extend the length of pregnancyPregnancy and control pain as much as possible. Recently, there have been studies that attempted prophylactic medical treatment due to the increase in the frequency of cholesterol gallstoneGallstones due to rapid weight lossWeight loss. This chapter demonstrates the pathogenesisPathogenesis and treatmentTreatment of GB stones in various conditions.
Article
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Gallstones are one of the most common diseases worldwide. Recently, the incidence of gallstones has increased and the pattern of gallstones has changed in Korea. Laparoscopic cholecystectomy is the standard treatment for symptomatic gallstones. Expectant management is considered the most appropriate choice in patients with asymptomatic gallstones. The dissolution of cholesterol gallstones by oral bile acid, such as ursodeoxycholic acid, can be considered in selected patients with gallstones. Although the advent of laparoscopic cholecystectomy has moved interest away from the pharmacologic treatment of gallstones, several promising agents related to various mechanisms are under investigation.
Chapter
Rowachol, a proprietary mixture of the six monoterpenes menthol, menthone, borneol, cineole, camphene and pinene in olive oil, reduced the lithogenicity of bile (Doran et al. 1979) and caused dissolution of cholesterol gallstones in man (Bell and Doran 1979). Daily administration of the drug (6–9 capsules) to 16 patients for periods of 2–28 weeks gave a progressive increase in serum HDL-cholesterol concentration with no accompanying change in the concentrations of serum total cholesterol or triglyceride (Bell et al. 1980) (Fig. 1). Similar effects in humans have been shown recently by Leiss and von Bergmann (1985) who administered Rowachol (200 mg t.i.d) to young healthy volunteers and measured a significant increase in the ratio of HDL-cholesterol to total cholesterol in serum.
Chapter
Until recently, cholecystectomy was the only treatment for gallstone disease. During the past 15 years, the discovery that gallstone patients have gallbladder bile that is supersaturated with cholesterol has led to the introduction of bile acid therapy aimed at desaturating bile and thus causing gallstone dissolution.
Chapter
Erhöhte Konzentrationen von Low density-Lipoproteinen (LDL) im Blut erhöhen das Risiko, eine koronare Herzkrankheit zu erwerben [1]. Diese klinischen Probleme haben zu Anstrengungen geführt, den Metabolismus der LDL und seine Rolle in der Regulation der Cholesterinbiosynthese besser zu verstehen. So gelang kürzlich der Nachweis, daß die Cholesterinbiosynthese in extrahepatischen menschlichen Zellen vor allem durch Cholesterin reguliert wird, das als LDL von der Zelle aus dem Plasma aufgenommen worden ist [2].