Latin American Journal of Pharmacy Original Article
(formerly Acta Farmacéutica Bonaerense)
Received: July 6, 2009
Lat. Am. J. Pharm. 29 (1): 79-86 (2010) Accepted: August 17, 2009
Sedative and Cardiovascular Effects of Aloysia citriodora Palau,
on Mice and Rats
María I. RAGONE, Mariana SELLA, Agustín PASTORE & Alicia E. CONSOLINI*
Cátedra de Farmacología, Área Farmacia, Departamento de Ciencias Biológicas,
Facultad de Ciencias Exactas, Universidad Nacional de La Plata,
47 y 115 (1900) La Plata, Argentina.
SUMMARY. Aloysia citriodora Palau, Verbenaceae (“cedrón”) is widely used as infusion or decoction in
South America to treat indigestion, tachycardia and anxiety. We previously demonstrated its antispas-
modic effect on rat duodenum. Now, its aqueous extract (AEC) from 1 to 10 mg/kg was sedative in mice on
the open-field, effect which was potentiated by diazepam and sensitive to flumazenil. In normotensive rats,
1 to 30 mg AEC/kg induced a transitory hypotension, insensitive to atropine and L-NAME. Regarding an
effect on α-adrenergic receptors, AEC non-competitively blocked the phenylephrine contraction on vas
deferens. In isolated rat hearts, AEC induced negative inotropism, as well as vitexin, the main component.
Then, the benzodiazepine-like sedation, negative inotropism and antispasmodic effect preclinically justify
its popular use for abdominal cramps and as coadjuvant for anxiety and angor.
INTRODUCTION identified in the leaves 10,11. As reported in a
Aloysia citriodora Palau, Verbenaceae (syn. previous work 6, the HPLC fingerprint of our
Aloysia triphylla L´Hér.) is a South American sample of “cedrón” showed the presence of the
plant, popularly known as “cedrón”, “hierba flavonoids vitexin and isovitexin, the first of
Luisa” and “verbena aromática” around the Rio both had antispasmodic properties. Also, it was
de la Plata, and “cidrao” and “lemon verbena” in reported that vitexin has antioxidant effects 12.
Brazil 1. In Argentina it is widely used as an aro- On the other side, cardiovascular diseases
matic leaves infusion or as a decoction for ab- dependent on stress are very frequent, and need
dominal pain, nausea and dizziness 1-4. Its daily to cronically use medicines and changing of the
consumption as dietary supplement was extend- way of life, especially food. Then, it is important
ed on sale at supermarkets. In Cuba it is used as to find phytotherapies which contribute to treat
expectorant and against insomnia, in Paraguay them with less adverse effects than synthetic
against tachycardia 5, and also for anxiety and drugs. In this work, the pharmacological basis
headache 1. We have recently demonstrated the for the popular use of “cedrón” for restless and
antispasmodic effects of A. citriodora, which tachycardia was studied from an aqueous ex-
was mainly attributed to intestinal relaxation by tract (AEC) on the spontaneous activity of con-
opening of K+ channels 6. scious mice and the blood pressure of nor-
About the composition, verbascoside and motensive rats. Protocols for the underlying
other volatile compounds as neral and geranial mechanisms were done in isolated preparations,
were identified in the essential oil 5,7-9 . A and it was also evaluated whether vitexin was
flavonoid, luteolin-7-diglucuronide, it was also the component responsible for the effects.
KEY WORDS: Aloysia citriodora, Cardiac inotropism, Hypotensive, Open-field, Sedative, Vitexin.
* Author to whom correspondence should be addressed. E-mail: dinamia@biol.unlp.edu.ar
ISSN 0326-2383 79
RAGONE M.I., SELLA M., PASTORE A. & CONSOLINI A.E.
MATERIAL AND METHODS 4 groups of mice, respectively administered with
Plant and extracts 33, 100 and 333 mg/kg of vitexin (Extrasyn-
A commercial sample of Aloysia citriodora these, France) or saline solution (negative con-
Palau (Verbenaceae) from Paraguay was provid- trol), for the times of 30, 60, 90 and 120 min af-
ed by a local herboristery, and the plant was au- ter the administration.
thenticated by Prof. Dra. Etile Spegazzini, from
the Herbarium Museum of Botany and Pharma- Blood pressure in rats
cognosy, Facultad de Ciencias Exactas, Universi- As in previous works 15, normotensive rats (n
dad Nacional de La Plata, Argentina, where the = 6) were anesthetized with 1.5 g/kg urethane
voucher specimen (herbarium number LPE (Fluka) by via i.p. and placed in a supine posi-
1039) was kept. An aqueous extract of A. citri- tion with tracheal cannulation. Blood pressure
odora or “cedrón” (AEC) was prepared by boil- (BP) was directly measured through an hep-
ing 30 g dried leaves in 200 ml distilled water arinized cannula in the internal carotid artery
for 20 min, as the ethnomedicinal use. After fil- connected to a Bentley 800 pressure transducer.
tration the decoction was lyophilized, obtaining It was continuously recorded on a Beckman
a 15% w/w yield. The lyophilized extract was polygraph and A/D converted by a National In-
diluted in distilled water or Krebs solution, re- struments Ni-DAQ with a PC516 logger to a
spectively for in vivo or in vitro tests the day the computer, and expressed in mm Hg. BP pulses
experiment was carried out. With this proce- were continuously recorded and the heart rate
dure, the essential oil is not included in the (HR) was calculated. Without treatment, BP re-
lyophilized sample. mained constant for at least 3 h. Drugs were i.v.
infused via the jugular vein in volumes of 0.1 ml
Animals separated by not less than 15 min. After 30 min
Swiss albino mice, weighing 25 to 30 g and of stabilization, doses of 1, 3, 10 and 30 mg lio-
Sprague-Dawley rats of 220-260 g weight, kept phyilized/kg were successively administered. Af-
under controlled conditions (12 h dark-light cy- ter other 30 min stabilization, 1.5 mg/kg at-
cle, 20-25 °C, fed ad-libitum on standard pellets ropine (Sigma, USA) was i.v. administered, fol-
and water) were used. All experiments were lowed by the same doses series of AEC. Finally,
conducted in accordance with internationally ac- after 30 min, 25 µmol/kg L-NAME (Sigma, USA)
cepted principles for laboratory animal use and was i.v. administered, followed by the same
care as was established by US guidelines (NIH doses series of AEC. A group of 4 rats was simi-
publication # 85-23, revised in 1985) 13. larly treated with saline solution instead of AEC,
as a negative control, and other group was treat-
Open-field test in mice ed with 10 µg/kg acethylcholine bromide (Sig-
The spontaneous locomotion and explorato- ma, USA) before and after the infusion of 1.5
ry activity of mice was evaluated on the open mg/kg atropine (positive control).
field, consisted of a 30 x 50 cm white box with
walls of 27 cm height divided in 15 squares of Rat vas deferens
10 cm2 by black lines. It was placed in a light To evaluate whether the hypotensive effect
and sound-attenuated room. Mice were divided of AEC was due to an antiadrenergic mecha-
in 7 groups, respectively for the following treat- nism, the effect of AEC was evaluated on the
ments: saline solution (negative control), 10 dose-response curves (DRC) of phenylephrine
mg/kg diazepam (positive control), 0.15, 1 and (Phe, Sigma, USA) in the rat vas deferens,
10 mg/kg AEC, 1 mg/kg AEC 5 min after receiv- preparation that has α-1 receptors. Vas deferens
ing 10 mg/kg diazepam (Roche, Argentina), and was isolated from male rats and submerged in
1 mg/kg AEC 5 min after receiving 0.5 mg/kg organ-baths containing 20 ml Krebs solution, at
flumazenil (Richmond, Argentina). All drugs 32 °C, preloaded with 0.5 g, and bubbled with
were administered by i.p. injections in a volume 95% O2-5% CO2. The Krebs solution composi-
of 0.1 ml by 10 g of weight. After 40 min, each tion was (in mM): NaCl 118, NaHCO 3 25,
animal was placed in the same corner of the KH2PO4 1.2, KCl 4.7, CaCl2 2.5 y Glu 11.1 (pH
field, and during 5 min there were counted the 7.4). DRC of Phe was done by cumulatively
number of crossed lines, rearings, grooming and adding 0.2 ml of the following solutions: 1, 2, 7,
other signs 14. This routine was repeated for ev- 20, 70, 200, 700 y 1000 µg/ml to the chamber
ery mouse at 80, 120 and 160 min from the ad- bath. Isometric contractions were measured by
ministration. The same protocol was done with isometric transducers FORT10 from WPI cou-
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Latin American Journal of Pharmacy - 29 (1) - 2010
pled to a Transbridge TBM 4M preamplifier RESULTS
(WPI, USA) and A/D converted by Eagle soft- Central effects of A. citriodora and vitexin
ware to a computer. AEC was added 10 minutes The exploratory behaviour and the sponta-
before the DRC, respectively at 0.20, 0.60 or 2.0 neous locomotion of mice were measured in the
mg lyophilized/ml. open field. Both properties, respectively mea-
sured by the number of rearings and crossed
Isolated rat hearts lines during 5 min, were dose-dependently de-
It was evaluated whether the extract of A. creased by AEC (Fig. 1). There were not signifi-
citriodora or vitexin have a direct effect on cant effects in grooming, which was poor still in
hearts, and whether the antioxidant properties control mice (results not shown). Both effects of
of the flavonoid protect hearts from the is- AEC 1 mg/kg on locomotion and exploration
chemia. Beating hearts were rapidly excised were potentiated by 10 mg/kg diazepam and in-
from heparinized (2000 U) rats after anesthesia hibited by 0.5 mg/kg flumazenil, especially at
with pentobarbital sodium overdose, as in a the start of the test (Fig. 1).
previous work 16. Hearts were perfused by Lan-
gendorf method with control Krebs at a constant
rate (6 ml/min/g) at 30 °C. The perfusate was a a
Krebs solution containing (in mM): 1 MgCl2, 120
NaCl, 0.5 NaH2PO4, 6 KCl, 2 CaCl2, 25 NaHCO3,
and 6 dextrose, bubbled with 95% O2-5 % CO2
to achieve a pH of 7.3-7.4. Atria were dissected
to prevent spontaneous contractions. A latex
balloon was placed into the left ventricle and
connected to a Bentley 800 pressure transducer
for measuring the left ventricular pressure (LVP).
Hearts were electrically stimulated with pulses
of 5 V-5 ms at 1 Hz. The LVP signals were con-
tinuously recorded as described for BP. The
maximal pressure developed during a beat (P)
was calculated from the recording as a differ-
ence between the maximal peak and the basal
LVP. Without treatment, P remained constant by b
4-5 h. After a 30-min equilibration period (dur-
ing which optimal diastolic volume was regulat-
ed until P reached a steady value), one of the
following protocols was done: (a) Perfusion
with Krebs and consecutively with 0.2, 0.6, 2,
and 6 mg AEC /ml; (b) Perfusion with Krebs
and 10 µM vitexin, then exposing hearts to no-
flow ischemia (I) during 45 min (by stopping
the perfusion), and to reperfusion (R) with
Krebs during other 45 min. A negative control
group was done with no-pretreatment before
the exposition to I-R (non-pretreated hearts).
Figure 1. Effects of AEC (acqueous extract of A. citri-
Statistical analysis odora) on spontaneous locomotion (a, number of
Results were expressed as mean ± S.E.M. cross lines during 5 min, two-way ANOVA: by time: F
Multiple comparisons between treatments which = 10.92, df = 3, p < 0.0001, by treatment: F = 33.83, df
were determined at several times or doses were = 6, p < 0.0001) and exploratory behavior (b, number
of rearings in 5 min, two-way ANOVA: by time: F =
done by two-way ANOVA tests followed by “a
5.897, df = 3, p = 0.0008, by treatment: F = 30.65, df =
posteriori” all paired Bonferroni tests, consider- 6, p < 0.0001) of mice vs. time. The negative (saline)
ing p < 0.05 for significance. Also, changes in and positive (diazepam) controls are shown. Results
BP were compared against zero by a Student t- are expressed as mean ± S.E.M (n = 5 to 7). A poste-
paired test. It was used the Prism GraphPad 4.0 riori Bonferroni tests: * p < 0.05, a p < 0.01, b p <
program for all tests. 0.001 vs. saline solution.
81
RAGONE M.I., SELLA M., PASTORE A. & CONSOLINI A.E.
Treatment 30 min 60 min 90 min 120 min
Saline (n= 8) 122.6 ± 9.4 84.9 ± 11.0 72.4 ± 8.8 52.1 ± 11.8
Vtx 33 mg/kg (n=8) 148.7 ± 13.4 101.5 ± 14.5 70.0 ± 7.3 73.6 ± 6.7
Vtx 100 mg/kg (n=10) 177.3 ± 18.5 * 123.3 ± 17.4 77.8 ± 12.3 80.2 ± 18.4
Vtx 333 mg/kg (n=9) 118.5 ± 6.7 85.8 ± 5.6 52.8 ± 10.6 43.0 ± 10.6
Table 1. Spontaneous locomotion (number of crossed lines in 5 min) produced by vitexin (Vtx) in mice during
the open field test. Two-way ANOVA: by time: F: 32.67, df 3, p < 0.0001; by treatment: F: 8.17, df 3, p < 0.0001;
*p < 0.05 vs Saline by Bonferroni test.
Treatment 30 min 60 min 90 min 120 min
Saline (n= 8) 36.4 ± 3.7 32.2 ± 4.4 19.9 ± 4.5 14.2 ± 4.3
Vtx 33 mg/kg (n=8) 46.1 ± 4.1 38.0 ± 4.8 25.9 ± 3.3 24.6 ± 4.2
Vtx 100 mg/kg (n=10) 39.8 ± 3.7 43.4 ± 4.5 31.0 ± 5.2 22.8 ± 5.8
Vtx 333 mg/kg (n=9) 41.5 ± 4.1 31.7 ± 3.8 22.3 ± 4.6 14.2 ± 3.9
Table 2. Exploratory behaviour (number of rearings in 5 min) produced by vitexin (Vtx) in mice during the
open field test.Two-way ANOVA: by time: F: 36.69, df 3, p <0.0001; by treatment: F: 1.648, df 3, p = 0.1986; NS
vs Saline by Bonferroni test.
Treatment [AEC] (mg/kg) Before AEC Hypotensive peak After 5 min n
– 1 235.3 ± 25.7 259.0 ± 30.0 250.0 ± 24.1 6
3 244.8 ± 24.1 231.0 ± 31.1 223.2 ± 26.7 5
10 234.5 ± 16.5 270.0 ± 60.2 247.0 ± 24.7 6
30 217.5 ± 11.7 225.0 ± 29.1 221.2 ± 15.3 6
atropine 1 315.0 ± 37.7 300.0 ± 58.7 315.0 ± 37.7 4
3 290.0 ± 26.4 280.0 ± 20.0 280 ± 20.0 3
10 307.5 ± 43.1 292.5 ± 30.9 315.0 ± 39.7 4
30 286.5 ± 46.2 300.0 ± 21.2 315.0 ± 39.7 4
L-NAME 1 232.5 ± 25.6 262.5 ± 22.5 262.5 ± 41.3 4
3 225.0 ± 28.7 247.5 ± 18.9 277.5 ± 22.5 4
10 230.0 ± 36.0 230.0 ± 10.0 185.0 ± 20.4 3
30 210.0 ± 21.2 202.0 ± 25.6 100.0 ± 17.3 * 4
2-way By treatment By doses: p = 0.78 By doses: p = 0.63,
ANOVA p = 0.0108 by treatment p = 0.052, NS by treatment: p= 0.0017
Table 3. Effects of AEC on the heart rate (HR) of anesthetized normotensive rats before and after treatment with
1.5 mg/kg atropine or 25 µmol/kg L-NAME. A posteriori test: * p < 0.05 vs. atropine + AEC 30 mg/kg.
The flavonoid vitexin only increased the The pre-treatment with 1.5 mg/kg atropine did
spontaneous locomotion at the start of the test not significantly change basal BP (ΔBP: 6.9 ± 6.9
and at 100 mg/kg, but not at higher doses or mm Hg) nor the effects of AEC, although it re-
longer periods of testing (Table 1). Moreover, duced the hypotension produced by acethyl-
vitexin did not modify the mice exploration choline (Ach) in the positive control group (Fig.
(Table 2). 2b). The administration of 25 µmol/kg L-NAME
increased basal BP (ΔBP: +33.75 ± 15.3 mm Hg)
Effects of A. citriodora on the blood but did not significantly change the effects of
pressure AEC (Fig. 2c). The transitory hypotension of
Basal BP of normotensive rats was 145 ± 27 AEC before and after atropine and L-NAME
mm Hg (n = 6). AEC induced a transitory hy- showed a dose-dependence but not differences
potension at 2.1 ± 0.21 s (n = 24), which re- among the 3 conditions (two-way ANOVA: by
turned to basal between 60 to 300 s (Fig. 2a). doses F = 3.852, df = 3, p = 0.014; by treatments:
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Latin American Journal of Pharmacy - 29 (1) - 2010
b Figure 3 . Dose-response curves of phenylephrine
(Phe, in µg/ml) on rat vas deferens in the absence
and the presence of AEC at 0.2, 0.6 and 2 mg liophyl-
ized/ml. Results are expressed as mean ± S.E.M (n =
7). Two-way ANOVA: by Phe-dose: F: 133.2, df 8, p <
0.0001, by AEC-treatment: F: 37.99, df 3, p < 0.0001.
A posteriori tests: * p < 0.001 vs. DRC control).
Effects of A. citriodora on adrenergic
receptors
Figure 3 shows that AEC non-competitively
inhibited the DRC of phenylephrine (Phe) (pD2
= -log EC50 (in M) = 4.8 ± 0.2), since it reduced
the Emax, Phe at 0.6 and 2 mg AEC/ml, suggest-
c
ing that AEC does not block the α-adrenergic
receptors. The inhibitory concentration of 25%
effect (IC25) obtained by extrapolating Emax vs
[AEC] was 0.499 ± 0.093 mg AEC/ml (n = 6).
Effects of A. citriodora and vitexin on
isolated rat hearts
Rat hearts developed contractions with P of
129.6 ± 21.4 mm Hg (n = 5) at the start of test.
Figure 2. Changes in blood pressure (BP, in mm Hg) Perfusion of AEC produced a concentration-de-
produced by i.v. infusion of AEC at doses of 1, 3, 10 pendent negative inotropism, which remained
and 30 mg/kg (initial ΔBP at 20-30 seg, and after 1 constant for 10-15 min (Fig. 4a). The main com-
and 5 min administration) on normotensive rats non- ponent of AEC, vitexin at 10 µM, did not signifi-
pretreated (a), pretreated with 1.5 mg/kg atropine (b) cantly reduce cardiac contractility of hearts (Fig.
and with 25 µmol/kg L-NAME ( c ). The negative 4b, initial P of 79.2 ± 15.0 mmHg, n = 6). Dur-
(saline) and positive (acethylcholine) controls were
ing the following I-R protocol, vitexin prevented
included. Student test: * p < 0.05 vs. zero.
the increase in diastolic resting pressure at the
start of R (ΔPr: + 12.8 ± 20.0 mm Hg, NS from
F = 1.643, df = 2, p = 0.2025). As a negative con- zero vs. 13.6 ± 5.7 mm Hg, p < 0.05 vs zero in
trol, 4 rats (basal BP: 125.6 ± 25.7 mm Hg) were control). Nevertheless, it did not significantly
injected with saline three times separated by 20 improve the recovery of P during R, in compari-
min, and the ΔBP was NS from zero (Fig. 2, son with the non-pretreated or negative control
saline group). group (initial P 112.8 ± 31.0, n = 6) (Fig. 4b).
Heart rate (HR) was significantly increased
by the pre-treatment with 1.5 mg/kg atropine, DISCUSSION
but not significantly modified by AEC at any In a previous work we demonstrated that the
dose, as neither after L-NAME (Table 3). aromatic plant A. citriodora Palau (“cedrón”
83
RAGONE M.I., SELLA M., PASTORE A. & CONSOLINI A.E.
a
leaves/kg), giving support to the soft sedative
properties for the “tea of cedrón”. Furthermore,
the sedative effect of 1 mg/kg AEC was potenti-
ated by diazepam and was reduced by flumaze-
nil, the antagonist of the benzodiazepine recep-
tor. These results suggest a benzodiazepine-like
effect of AEC on the GABA-A receptor. Never-
theless, the flavonoid vitexin previously identi-
fied in AEC 6 was not the responsible for such
sedative effects, since it did not decrease loco-
motion. This lack of effect is important when
considering that vitexin is a component of seda-
tive and anxiolytic plants from the Passiflora
genous, and it is especially the compound used
to quantify them 17. Thus, the reference com-
pound for the qualitative and quantitative analy-
b
sis is not the sedative active principle. Regarding
the sedative component of A. citriodora, it still
remains undetermined. Some compounds from
the “lemon verbena” essential oil were found,
such as limonene 7 and citral 4, which were re-
ported as sedative in the related genous Lippia
18, but it is expected that volatile components
may not remain in the AEC after decoction and
lyophilization. Luteolin-7-diglucuronide and ver-
bascoside were found in the infusion and leaves
of “lemon verbena” 7. Luteolin-7-diglucuronide
has also been isolated from Lippia alba and
demonstrated to bind the GABA-A receptors at
IC50 of 40-100 nM 19, which could explain the
effect that we found with AEC in the open-field.
Figure 4. Maximal left ventricular pressure develop- Taking into account the phylogenetic origin of
ment (P) of rat cardiac contractions as a percentage of secondary metabolites, it is important to consid-
its initial value, after perfusing: (a) A. citriodora as er that other South American related species
AEC at 0.2 to 6 mg lyophilized/ml (two-way ANOVA: (Aloysia polystachya) was also sedative in rats 20
by time: F = 6.15, df = 7, p < 0.0001, by treatment: F and has phenols and monoterpens in its compo-
= 72.36, df = 3, p < 0.0001, a posteriori test: a p < 0.01, sition 21. Then, it is possible that a combination
b p < 0.001 vs. AEC 0.2 mg/ml), and (b) vitexin 10 µM
of those compounds would be responsible for
during 15 min before exposing hearts to 45 min is-
chemia (I) and 45 min reperfusion (R) in comparison
the important sedative and benzodiazepine-like
with non-pretreated hearts (negative control) (two- effect of the acqueous extract of A. citriodora.
way ANOVA: by treatment: NS, by time: p < 0.0001). In normotensive rats, the i.v. administration
Results are expressed as mean ± S.E.M (n = 5-6). of AEC produced a transitory hypotension,
dose-dependent between 1-30 mg lyophilized/
kg. The time-course suggested an effect on mus-
from Paraguay) has antispasmodic effect on iso- carinic receptors or on nitric oxide (NO) release.
lated duodenum, which gives support to the use Nevertheless, neither the pretreatment with 1.5
for gastrointestinal disorders 6. Now, we preclin- mg/kg atropine or 25 µmol/kg L-NAME (com-
ically evaluated the basis for its use in anxiety petitive blocker of NO-synthase) changed the
and tachycardia. The present results show that hypotensive response to AEC, suggesting that it
AEC reduced the spontaneous locomotion and was not mediated by muscarinic receptors or
the exploratory behaviour of mice on the open the NO-synthase. Also, on the isolated vas def-
field, at doses (0.15 to 10 mg lyophilized/kg) erens, a smooth muscle which has α1 receptors
equivalents to 1-66 mg leaves/kg. These doses 22, AEC was a non-competitive inhibitor of the
i.p. administered to mice are lower than those phenylephrine dose-response curve, since it de-
orally used in humans (about 100 mg creased the maximal effect 23,24. This result sug-
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Latin American Journal of Pharmacy - 29 (1) - 2010
gests that AEC is not a α1-adrenergic antagonist, hearts, Fig. 4b). Consequently, vitexin is not the
but it directly affects the smooth muscle. It responsible of the negative inotropism of AEC,
agrees with the effect of AEC on intestines, but neither it is anti-ischemic. Regarding other
where we demonstrated the activation of sar- components, verbascoside was isolated from A.
colemmal K+-channels and guanylate-cyclase, citriodora 4,7 and demonstrated to be antioxi-
partially due to vitexin 6. Such a non-competi- dant 19,27. Also, verbascoside induced a positive
tive blockade of the adrenergic vascular tone inotropism in the isolated perfused hearts 28,29.
could cause at least part of the transitory hy- Contrarily, our sample of AEC induced a great
potension seen in normotensive rats. On this negative inotropism, suggesting that it would
connection, the most important component of have less verbascoside than other reported
AEC, vitexin, was reported as hypotensive and specimens. It could be possible that specimens
bradycardic at doses >10 mg/kg i.v., which was from different regions differ in composition, as it
not affected by bilateral vagotomy 25. Another has been described for the essential oil 9.
contribution to hypotension could be the nega-
tive inotropism of AEC seen on isolated rat CONCLUSIONS
hearts, although “in vivo” it did not significantly The aqueous extract of A. citriodora pro-
change the heart rate. If considering that the duced an important sedative effect on mice, by
doses of 1-30 mg/kg assayed on normotensive a benzodiazepine-like mechanism. Also, it in-
rats may be equivalent to about 0.067 to 2 duced a transitory hypotension in normotensive
mg/ml plasma (since a rat has about 3 ml plas- rats, which was not due to cholinergic effect,
ma) and the negative cardiac inotropism was NO-release or α1-adrenergic antagonism. In iso-
found at the doses of 0.6, 2 and 6 mg/ml, it is lated vas deferens the AEC showed a non-com-
expected that AEC could reduce the cardiac de- petitive contractile blockade, which agrees with
mand. Then, both the cardiovascular and seda- the antispasmodic effect previously seen in in-
tive effects of AEC give support to the use of testine. In vivo, AEC did not modify heart rate
the “cedrón tea” as a coadjuvant for the treat- but in vitro it induced a dose-dependent nega-
ment of angor. tive cardiac inotropism, which could contribute
By other side, certain flavonoids showed an- to the transitory hypotension, and gives support
tioxidant activity 12,19, potentially giving protec- to the use of A. citriodora (South American “ce-
tion against coronary diseases. When the drón”) as a coadjuvant for treating angor and
flavonoid vitexin was evaluated on isolated rat anxiety. Nevertheless, the main flavonoid found
hearts, it did not significantly change the in- in this sample and known as hypotensor, vitex-
otropism, which agrees with previous reports 26. in, had not sedative effects or cardiac antiis-
Moreover, in a model of ischemia-reperfusion chemic properties.
vitexin slightly prevented hearts from the post-
ischemic diastolic contracture, but not from the Acknowledgments. This work was supported by a
decrease in contractility seen in the negative grant from Universidad Nacional de La Plata (11-X-
control (regarding non-pretreated reperfused 408, 2005-2008), Argentina.
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