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381
JPP 2004, 56: 381–387
ß
2004 The Authors
Received August 07, 2003
Accepted December 04, 2003
DOI 10.1211/0022357022917
ISSN 0022-3573
Department of Pharmacology,
Faculty of Medicinal Sciences,
Paramaribo, Suriname
J. A. Hasrat
Department of Pharmaceutical
Sciences, University of Antwerp,
Universiteitsplein 1, B-2610,
Antwerp, Belgium
L. Pieters, A. J. Vlietinck
Correspondence: A. J. Vlietinck,
Department of Pharmaceutical
Sciences, University of Antwerp,
Universiteitsplein 1, B-2610,
Antwerp, Belgium.
E-mail: arnold.vlietinck@ua.ac.be
Acknowledgment: The
manuscript of this paper was
critically commented by
Prof. Emeritus Dr E. L. Noach,
former Head of the Department
of Pharmacology from the
Faculty of Medicine of the State
University of Leiden, the
Netherlands, for which we are
indebted.
Medicinal plants in Suriname: hypotensive effect
of
Gossypium barbadense
J. A. Hasrat, L. Pie ters and A. J. Vlietinck
Abstract
In traditional medicine Gossypium barbadense L. is used against hypertension. Looking for a scientific
basis for this use, the blood-pressure-lowering effect of the decoction of the leaves was confirmed.
Fraction II (frII) of the crude extract of G. barbadense showed a dose-dependent hypotensive effect in
anaesthetized rats. In hexamethonium-treated rats, the blood-pressure-lowering effect of frII was
almost abolished. A small decrease of the blood-pressure-lowering effect was followed by an increase
in the blood pressure. Phentolamine antagonized the increase in blood pressure in hexamethonium-
treated rats. High doses of atropine (4 mg/rat) suppressed both depressor and heart effects. In-vitro
experiments revealed that atropine did not antagonize the contraction of the ileum of the rat.
Tripelennamine in a concentration of 100 ·g could not influence the contraction either, whereas
300 ·g did. In the guinea-pig ileum 10 ·g tripelennamine did not reduce the contraction significantly.
In the mechanism of action of frII, acetylcholine receptors could be involved, but not histami-
nergic or adrenergic receptors. Although it is still not known which compound(s) in G. barbadense is
(are) the active substance(s), the results obtained may explain the use of this plant in traditional
medicine in Suriname.
Introduction
The application of medicinal plants and herbal remedies has become popular worldwide
and is increasing both in developing and developed countries. About 20 000±40 000
plants are used for medicinal purposes; most of these are used in traditional systems of
medicine as well as in the cosmetics, nutrition and essential oils industry (Hasrat 1997).
Nowadays, scientific research into medicinal plants is carried out on a larger scale than
ever before. The main reason is that, notwithstanding the great progress in biotechnol-
ogy, there has not been a breakthrough to produce better, specific and safe drugs.
In Suriname, located on the northern coast of South America and rich in natural
resources, the application of traditional medicine has been known since the discovery
of the Guyanas. All of the ethnic groups from other continents that have settled in
Suriname have added to the rich and various traditional medicine culture that exists
now. There is, however, a lack of scientifically based information on traditional
medicine in this country, especially regarding medicinal plants. The scientific investi-
gation of medicinal plants in Suriname was based on information gathered in the
publication of Heyde (Hasrat 1997).
Many inhabitants in the interior of Suriname, and even urban inhabitants, are
deprived of a good and regular public health service, due to lack of proper communica-
tion and transport and the economical situation of the country. Reliable information
about the natural products of Suriname and traditional medicine can be used by public
health workers and in general by all inhabitants, for the treatment of common diseases.
Therefore, in light of the recognized value of medicinal plants in the treatment of several
diseases, much more scientific investigation must be conducted (Hoareau & DaSilva
1999; Ernst 2003).
In Suriname, although it is a developing country, the prevalence of hypertension is
relatively high. The impression is that the incidence is the highest among those descended
from African origin, although this has not been confirmed scientifically. It is by these
people that herbal products are frequently used, as part of
their traditional medicine, for the treatment of symptoms
that might be due to hypertension. Gossypium barbadense L.
(vernacular name, redi katoeng or red cotton), a member of
the Malvaceae family, is one of the plants used for this
purpose (Morton 1981; Heyde 1985). A decoction or an
infusion of the leaves from this plant is used.
This investigation has been initiated w ith the objective
of finding a scientific basis for the claim that G. barba-
dense lowers blood pressure. Elucidation of the pharma-
cological mechanism might provide new insight into the
pathophysiology and the treatment of hypertension.
Isolation of active components could then lead to the
development of new therapeutics. Due to the worldwide
renewed interest in medicines of natural origin, the devel-
opment of a suitable therapeutic from G. barbadense may
have economic benefit for Suriname.
The blood-pressure-lowering effect of G. barbadense
has never been described before in scientific literature.
There has not been a thorough description of the phyto-
chemistry of the plant. Gossypol, a toxic (carcinogenic)
compound, as well as some other compounds, has been
detected in cotton seed (Morton 1981).
In the first report we have focused on the ethno-phar-
macological claim and in the near future we hope to
present the isolation of the active compound(s).
Materials a nd Methods
Materials
Materials used were: frII (500, 1500, 5000
·
g mL
¡
1
);
isoprenaline (10
·
g mL
¡
1
); noradrenaline (epinephrine)
(10
·
g mL
¡
1
); hexamethonium (25 mg mL
¡
1
); acetylcholine
(1500
·
g mL
¡
1
); phentolamine (10 mg mL
¡
1
); tripelenna-
mine; BaCl
2
(2 mg mL
¡
1
); urethane; heparin; histamine;
and solutes for different buffers. Every test solution was
prepared in buffered salt solution, pH 7.4.
Plant extracts
Gossypium barbadense L. (Malvaceae), identified by
M. Werkhove from the herbarium of the University of
Suriname, where a voucher specimen is kept, was collected
in one of the dry seasons (October/November) in a village
about 20 kilometers from the Surinamese capital,
Paramaribo.
The nervation of the leaves was removed, the leaves
were then washed in distilled water, crushed in a blender
and centrifuged at 8000 rev min
¡
1
. The liquid was evapo-
rated under reduced pressure at a temperature of 50
¯
C,
almost to dryness. Finally, the concentrated solution was
frozen in liquid nitrogen and freeze-dried.
Purification procedure
Column chromatography with Al
2
O
3
neutral (super I
activity), obtained from Merck, was the first step in the
purification of the decoction, after it was established that
the blood-pressure-lowering effect was still present when
column chromatography was performed with neutral and
acid Al
2
O
3
, and not with basic Al
2
O
3
. The elution was
performed with water. The polar compounds present in
this eluate were subjected, after concentration, to high-
pressure liquid chromatography (HPLC) on a semi-pre-
parative reversed-phase column ( 10
·
m). The elution was
performed with 20% methanol and subsequently pure
methanol, using a flow speed of 4 mL min
¡
1
with UV
(254 nm) detection. The 20% methanol eluate was sepa-
rated after 1 min 42 s in two fractions (fraction I (frI) and
fraction II (frII)), and methanol eluate was collected as one
fraction (frIII). After evaporation of methanol in the three
fractions, under reduced pressure, the remaining water was
freeze-dried. Quantities of the three fractions were dis-
solved in buffered salt solution, pH 7.4, and the test solu-
tions were obtained through dilutions with the same buffer.
Experimental protocols
The in-vivo pharmacological experiments were performed
to measure the blood-pressure-lowering activity of the
crude extract and purified fractions of G. barbadense
and to investigate the site of action (hexamethonium experi-
ments) and the mechanism of action (atropine experiments),
whereas the in-vitro experiments (histamine experiments)
were performed to investigate only the mechanism
of action. The blood-pressure-lowering activity was used
as method for the bio-guided isolation of active com-
pounds.
The animals used in the experiments were kept under
controlled lighting conditions in a temperature-controlled
environment (22
¯
C). The animal quarters were illuminated
from 0600 to 1800 h. Food and water were freely available.
In-vivo experiments
Wistar rats, 180±280 g, were used. The blood-pressure
experiments were performed using anaesthetized rats. Ure-
thane was used as the anaesthetic; 0.1±0.2 mL/100 g rat
from a 160 g/100 mL urethane solution was injected intra-
peritone ally. C atheters containing heparinized (50 U mL
¡
1
)
saline were inserted into the right carotid artery and the
right external jugular vein for blood-pressure measurement
and intravenous administration of drugs, respectively. The
arterial catheter was connected to a Statham P23AA pres-
sure transducer and mean arterial blood pressure was
derived from the direct measurement. The pressure trans-
ducer was connected to a Sandborn pre-amplifier and the
blood pressure was subsequently registered on a Sandborn
recorder. The recorder was calibrated before every experi-
ment in which the blood pressure was measured in mmHg.
The heart frequency was derived from the blood pressure
recording or by electrodes connected to the paws of the
rat.
In each experiment control measurement s were initially
performed. First, the application of buffered salt solution,
pH 7.4, followed by 10
·
g of isoprenaline, a non-selective
-adrenergic receptor agonist, and noradrenaline (nor-
epinephrine), respectively, to verify if the cardiovascular
382 J. A. Hasrat et al
system was responding to blood-pressure-active substances.
Next, the different dosages of frII were applied at random.
In the hexamethonium experiments, artificial respiration
was used before hexamethonium (20 mg), a blocker of
ganglia of the autonomic nervous system, was applied.
Thereafter, several dosages of frII were applied at random.
In the atropine experiments, the procedure was fol-
lowed by the application of acetylcholine (150
·
g).
Atropine (4 mg), an antagonist of the muscarinic-type
receptors of acetylcholine, was then applied followed by
the same dosage of acetylcholine to check the blockade of
the muscarinic receptors. Thereafter, the different dosages
of frII were applied at random.
At the end of every experiment, 10
·
g of isoprenaline and
noradrenaline, respectively, were again applied to investigate
changes in the cardiovascular performance of the rat. The
application of any substance in the experiments was made
after the blood pressure had returned to the value before the
application or had stayed constant at that or another value
for at least 5 min.
In-vitro experiments
Ileum of rats, 200±280 g, and one guinea-pig, 300 g, were
used. The animals were killed by a blow on the head and
cutting the throat. Through a midline section of the abdo-
men, a piece of terminal ileum was cut off and rinsed with
Tyrode’s buffer (Perry 1970). This piece of ileum was
further divided into smaller pieces with which the experi-
ments were performed. The perfusion fluid was oxy-
genated Tyrode’s buffer that was applied from the
reservoir and warmed to 37
¯
C by water circulating from
a thermostat. For isotonic contraction measurements, one
end of a piece of ileum was attached by a thread to a fixed
pin in the glass organ-bath, the other end was attached by
a thread to an iron rod, which was further connected by a
thread, walking over a wheel, to a fixed load (1 g). The
iron rod moved in a magnetic field w hen the length of the
piece of ileum changed. These movements caused small
electrical currents that were amplified by a Sandborn pre-
amplifier and registered on a Sandborn recorder. The
change of the length of the organ was expressed as the
change in mm on the recorder at a fixed attenuation level.
Each test material was administered in volumes of
0.1 mL to the organ-bath solution. Before the application
of atropine the ileum was washed three times, and after each
administr ation of atropine the ileum was washed five times.
After application of buffered salt solution, the different
dosages of frII used in these experiments were applied at
random. Acetylcholine, 100
·
g, was then applied followe d
by 10
·
g of atropine and 100
·
g of acetylcholine, the latter
to check muscarinic receptor blockade. Next, 10
·
g of
atropine was applied to the organ bath solution before
each of the dosages of frII was administered.
Results
After confirming the blood-pressure-lowering effect of
the crude extract of G. barbadense and the neutral Al
2
O
3
column elution sample, HPLC reversed-phase column
chromatography fractionation was performed. Three frac-
tions were collected ± two 20% methanol fractions and
one methanol fraction.
Blood-pressure-lowering effect of frII
There was a dose-dependent decrease of the blood pres -
sure with frII in anaesthetized rats (Table 1).
Hexamethonium experiments
These experiments were conducted to investigate the site of
action (central nervous system (CNS) or peripheral) of frII.
The results (Table 2; Figure 1) showed that hexamethonium
abolished the effect of frII (Table 2, column III); moreover,
frII had opposite effects (Table 2, column IV). The increase
of blood pressure in the presence of hexamethonium was
dose dependent and was suppressed by phentolamine, a
non-selective
¬
-adrenergic receptor antagonist (results not
presented). Phentolamine was introduced after the last
application of frII in the hexamethonium experiments.
Atropine experiments
Atropine (10
·
g) completely antagonized the blood-pres-
sure-lowering effect of acetylcholine, decreased the effect of
isoprenaline significantly and diminished the effects of the
doses of frII (Table 3). Moreover, in the presence of atropine,
frII caused first a small decrease in blood pressure followed
by an increase. The frII dose-dependent decrease of the heart
frequency was also completely antagonized by atropine.
Interaction of propranolol and phenoxybenzamine
in rats with the action of frII
In a few experiments conducted with frII (results not
shown) in the presence of propranolol, a non-selective
-adrenergic receptor antagonist, it was observed that
Table 1 Dose±response relation of frII in anaesthetized rats.
Compound
D
Blood pressure (mmHg)
1 ·g Isoprenaline ¡42 § 10
1 ·g Noradrenaline 47 § 9
Control ¡2.5 § 1.1
5 ·g frII ¡1 § 1
15 ·g frII ¡5 § 6
50 ·g frII ¡15 § 5*
150 ·g frII ¡26.3 § 6.0
500 ·g frII ¡36 § 13**
Anaesthesized rats, initial blood pressure 124 § 11 mmHg, received
frII dosages at random after the response to administration of
isoprenaline and noradrenaline was determined. Data are
means § s.e.m ., n ˆ 6. Analysis of variance one-pair test was
applied; *P < 0.05, versus control and 50 ·g frII; **P < 0.05,
versus 50 ·g frII and 500 ·g frII.
Hypotensive effect of
Gossypium barbadense
383
the effects of frII (50
·
g and 150
·
g) w ere not reduced
after addition of both 100
·
g and 200
·
g propranolol.
Phenoxybenzamine, a non-competitive, non-selective
¬
-
adrenergic receptor antagonist, 100
·
g/100 g intraperito-
neally, administered 20 h and 1 h before administration of
frII (50
·
g and 150
·
g), did not influence the effect of frII,
but completely abolished the blood-pressure-increasing
effect of adrenaline.
In-vitro experiments
Isolated ileum experiments
Atropine did not antagonize the effects of frII on the
ileum of the rat (Table 4). Instead, it potentiated the
contraction of frII. Although tripelennamine antagonized
the effects of frII on rat ileum (Table 4), the number of
experiments was too small to draw any conclusion. In
guinea-pig ileum, the dose±response relation of frII
showed a biphasic pattern, different from that of hista-
mine. Moreover, the guinea-pig ileum was much less sen-
sitive to frII than histamine (Figure 2).
Discussion
The use of phytotherapeutics is increasing worldwide. So,
the need for scientifically collected data on these products
is in conjunction with these demands. Ignoring these facts
is wrong and does not help to collect reliable information
on these therapeutics for the public health in general
(Ernst 2003). This study was, therefore, conducted to
find scientific evidence for the claims of traditional med-
icine practitioners that red cotton, Gossypium barbadense
L., possesses blood-pressure-lowering effects. In addition,
the isolation of active compounds could lead to new effec-
tive therapeutics for the treatment of hypertension.
From the crude extract of G. barbadense, which pre-
viously had shown blood-pressure -lowering effects in
anaesthetized rats, frII was collected as the most active
Table 2 Hexamethonium experiments in anaesthetized rats: determination of the site of action of frII.
Before hexamethonium application After hexamethonium application
¢ Blood pressure
(mmHg)
¢ Heart frequency
(beats per min)
¢ Blood pressure
(mmHg)
¢ Heart frequency
(beats per min)
I II III IV V VI
1 ·g Isoprenaline ¡54.2 § 4.4 ‡24 § 10 ¡23.3 § 3.5
1 ·g Noradrenaline ‡29.7 § 1.3 ¡4 § 3 ‡55.6 § 2.6
Control 0 0 0 0 0 0
50 ·g frII ¡36.0 § 2.3 ¡4 § 2 ¡5 § 3.6 0.8 § 0.8 ¡1 § 1 ‡1 § 1
150 ·g frII ¡45.3 § 2.5 ¡14 § 3 ¡3.9 § 3.4 ‡17.7 § 2.2 ¡3 § 2 ‡6 § 3
500 ·g frII ¡47.7 § 2.2 ¡70 § 23 ¡4.0 § 4.0 ‡38.3 § 3.3 ¡2 § 2 ‡16 § 8
Anaesthetized rats, receiving artificial respiration after treatment with hexamethonium (20 mg), were administered frII dosages at random.
Data are means § s.e. m., n ˆ 6. The data were compared with those before hexamethonium treatment. The initial blood pressure and heart
frequency before introduction of hexamethonium were 127.3 § 3.2 mmHg and 372 § 40 beats per min, respectively. After treatment with
hexamethonium these were changed significantly (P < 0.05) to 79.2 § 7.8 mmHg and 302 § 14 bea ts per min, respectively. Analysis of va riance
one-pair test exhibited a significant difference (P < 0.05) between the responses to frII dosages before hexamethonium, except 150 ·g frII vs
500 ·g frII. After treatment with hexamethonium, the frII responses were significantly different (P < 0.01), a s before treatment. No significant
differences were measured (P > 0.05) between the blood-pressure-lowering effects of the frII dosages, but the blood-pressure-increasing effects
of the frII dosages were significantly different (P < 0.05) after t reatment with hexamethonium.
–60
–50
–40
–30
–20
–10
0
10
20
30
40
50
50 150 500
Dose (
m
g)
D
Blood pressure (mmHg)
Figure 1 Site of action of frII: influence of hexamethonium on the
effects of frII in anaesthetized rats.
^
, frII; &, frII decrease in
blood pressure after hexamethonium; ~, frII increase in blood pres-
sure after hexamethonium. The blood-pressure-decreasing effects of
frII in the presence of hexamethonium have changed significantly
into first a non-dose-dependent much lesser decrease in the blood
pressure and thereafter a dose-dependent blood-pressure-inc reasing
effect that is shown separately. The data are presented as means
§ s.e.m., n ˆ 6.
384 J. A. Hasrat et al
fraction after HPLC purification procedure. The pharma-
cological data presented here were collected from experi-
ments with this H PLC fraction.
This study was carried out following a classical pharma-
cological approach. First, the interaction between active
compound(s) in frII and a receptor was established through
investigation of the dose dependency of the response. The
response t o a ligand is proportional to the number of recep-
tors occupied by the ligand at equilibrium (Williams 1991).
The dose±response relation of frII (Table1) gives hard evi-
dence that in the extract of G. barbadense, at least one
compound with a blood-pressure-lowering effect is present.
Second, the site of action was investigated through the
experiments with hexamethonium, which showed that,
with regard to the blood-pressure-lowering effect of frII,
the receptor is likely to be present in the CNS. The physio-
logical effects after administration of hexamethonium can
be attributed to the blockade of transmission in ganglia of
the autonomic system (Taylor 1980; Rang et al 1999a).
Centrally acting antihypertensive drugs produce their effects
Table 3 Mechanism of action: interaction of atropine with the cardiovascular effects of frII in anaesthetized rats.
D
Blood pressure (mmHg)
D
Heart frequency (beats per min)
Before atropine After atropine Before atropine After atropine
1 ·g Isoprenaline ¡48.2 § 4.2 ¡12.2 § 4.1 ‡13 § 5 ‡6 § 4
1 ·g Noradrenaline ‡29.2 § 4.4 ¡8 § 5
Control ¡0.7 § 0.7 ¡1 § 0.8 0 0
50 ·g frII ¡27.2 § 5.7 ¡6.8 § 4.5 ¡2 § 2 ¡2 § 2
‡0.3 § 0.3
150 ·g frII ¡35.7 § 5.1 ¡9.5 § 6.0 ¡26 § 19 ¡2 § 2
‡2.2 § 1.6
500 ·g frII ¡43.2 § 3.7 ¡5.4 § 3.3 ¡106 § 48 ‡7 § 7
‡8.6 § 2.8
150 ·g Acetylcholine ¡64.2 § 2.8 ¡2.3 § 2.3 ¡273 § 18 0
‡4.0 § 2.8
After anaesthetized rats had received atropine (4 mg), the blood-pressure-lowering effects of frII were changed significantly
(P < 0.01; analysis of variance one-pair test). Data are means § s.e.m., n ˆ 6. The initial blood pressure decreased
significantly (P < 0.01) from 110.8 § 4.9 to 73.2 § 9.1 mmHg. The heart rate was not influenced, 331 § 17 beats per min
before, and 328 § 17 beats per min after atropine.
Table 4 Mechanism of action of frII: effects of frII in the ileum of
the rat after treatment with atropine.
Change in ileum length (mm)
Before atropine After atropine
150 ·g frII 16 § 5 25 § 5
100 ·g Acetylcholine 90 § 10 0
Rat ileum preparations (see text for more details) were exposed
to frII before and after treatment of atropine (10 ·g). The response to
frII was increased, but not significantly (P > 0.05). The effect of
acetylcholine was completely inhibited. The change in the length
of the ileum was expressed as the c hange in mm on the recorder
paper at a fixed attenuation level of the amplifier.
0
50
100
150
200
1
3
10
30
5
0
10
0
150
30
0
500
100
0
1
500
3000
5000
Dose (
m
g)
Contraction (mm)
Figure 2 Mechanism of action: dose±response curves of histamine
and frII on the guinea-pig ileum in the p resence and absence of
tripelennamine.
}
, histamine;
&
, histamine after administration of
tripelennamine;
~
, frII;
£
, frII after administration of tripelenna-
mine. Guinea-pig ilea were exposed to increasing dosages of frII and
histamine with or without tripelennamine (10 ·g), a histaminergic
receptor antagonist. The response to histamine was significantly
changed (P < 0.05; Student’s t-test), in the presence of tripelenna-
mine and the curve was shifted to the right. The response of the tissue
to frII was much smaller than to histamine and was not significantly
changed in the presence of tripelennamine. The change in the length
of the ileum was expressed as the change in mm on the recorder paper
at a fixed attenuation level of the amplifier. The data are presented as
means § s.e.m., n ˆ 6.
Hypotensive effect of
Gossypium barbadense
385
by reducing activity of the sympathetic nervous system
(Rang et al 1999b; Blaschke & Melmon 1980). The bradycar-
dia produced after application of frII (Tables 2 and 4) indi-
cated that the active compound acts in the CNS. There is also
a blood-pressure-increasing effect that is evident when the
blood-pressure-lowering effect is masked. The blood-pres-
sure-increasing effect is dose dependent, as is depicted in the
hexamethonium experiments (Figure 1). This action is antag-
onized by phentolamine, an
¬
-adrenergic antagonist. The
effects of frII on the blood pressure resemble the action of
clonidine; however, it is not excluded that the effects of frII
might be produced by more than one compound. Clonidine
has a blood-pressure-lowering effect, through action in the
CNS, and a blood-pressure-increasing effect, via
¬
-adrener-
gic receptors in the vessels (Blaschke & Melmon 1980).
The investigation of the mechanism of action of active
compound(s), as the third part of the classical pharma-
cological approach, revealed that
-adrenergic and
¬
-
adrenergic receptors are not involved.
-adrenergic recep-
tor stimulation in the vessels produces vasodilatation
and, consequently, a decrease in the blood pressure.
Stimulation of
¬
1
-adrenergic receptor increases the blood
pressure, while stimulation of
¬
2
-adrenergic receptors
decreases the blood pressure. In a number of experiments,
performed with propranolol and phenoxybenzamine, it
was shown that these compounds did not exhibit any
antagonistic action on the blood-pressure-lowering effect
of frII. In those experiments, the blood-pressure-lowering
effect of isoprenaline and the blood-pressure-increasing
action of adrenaline were completely antagonized by
propranolol and phenoxybenzamine, respectively, which
implies that none of the peripheral
-adrenergic and
¬
-adrenergic receptor types are involved in the blood-
pressure-lowering effect of frII. The
¬
-adrenergic receptor
types se em to be involved in the blood-pressure-increasing
effect of frII, because phentolamine, a competitive
¬
-adre-
nergic receptor antagonist, depressed this effect.
Further, atropine diminished the blood-pressure-low-
ering effects of frII, although the effect of isoprenaline was
also depressed. This antagonistic activity may be due to
action of atropine on the CNS, where a circuit that con-
trols blood pressure is influenced.
In-vitro experiments have shown dual effects of frII;
frII produces contraction in rat and guinea-pig ileum;
however, in the latter preparation a steady decrease of
the contraction at the highest doses is observed (Figure 2).
Atropine did not decrease the contraction produced by
frII at the ileum of the rat. The interaction with histaminic
receptors found in the experiments with tripelennamine
revealed an antagonistic activity with high doses of tripel-
ennamine, although the effects of frII on the ileum of the
rats were as small as with histamine.
The results of the experiments with guinea-pig ileum
showed a biphasic effect of frII. Tripelennamine interfered
with, but did not reduce completely, the contraction pro-
duced by frII. The combination of tripelennamine and
atropine gave an increased reduction of the effects of frII
on this preparation.
In the light of the above results, it may be concluded that
the extract of G. barbadense has blood-pressure-lowering
effects and so there must be at least one active compound
present in the extract. The blood-pressure-lowering effect is
produced through an action on the C NS. Moreover, the
effect on blood pressure is comparable with that of cloni-
dine, an
¬
2
-adrenergic receptor agonist (Blaschke &
Melmon 1980). The mechanism of action of the active
compound(s) must still be elucidated. Interaction with mus-
carinic receptors seemed to play a role, as was demonstrated
with the atropine experiments; however, an interaction with
histaminic receptors is not excluded. Further, an interaction
with adrenergic receptors could not be demonstrated.
More research has to be carried out to elucidate the
mechanism of action of the extrac t. Radioligand binding
studies, as performed with other plants (Hasrat et al
1997a, b, c, d, e), may contribute to solve this, whereas
the isolation of the active compound(s) will make the
interpretation of the results easier.
This is the first publication in which the blood-pres-
sure-lowering effect of G. barbadense has been described,
as is claimed in the traditional medicine.
References
Blaschke, T. F., Melmon, K. L. (1980) Antihypertensive agents,
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