Journal of Ethnopharmacology, 17 (1986) 37-64 Elsevier Scientific Publishers Ireland Ltd.

37

PHARMACOLOGY OF LEMONGRASS (CYMBOPOGON CZTRATUS STAPF). I. EFFECTS OF TEAS PREPARED FROM THE LEAVES ON LABORATORY ANIMALS*

E.A. CARLINI, JUIDA DE D.P. CONTAR, ARMANDO R. SILVA-FILHO, NYLSON G. DA SILVEIRA-FILHO, MARIO LUIZ FROCHTENGARTEN and ORLANDO F.A. BUENO

Departamento de Pslcobiologia, Escola Paulista de Medicina, Rua Botucatu, 862, 04023 S&o Paula - SP (Brazil)

(Accepted April 30,1986)

Summary

Cymbopogon citrutus is one of the most used plants in Brazilian folk medicine for the treatment of nervous and gastrointestinal disturbances. It is also used in many other places to treat feverish conditions. The usual way to use it is by ingesting an infusion made by pouring boiling water on fresh or dried leaves (which is called abafado in Portuguese). Abafados obtained from lemongrass harvested in three different areas of Brazil (Ceara, Minas Gerais and Slo Paulo States) were tested on rats and mice in an attempt to add experimental confirmation to its popular medicinal use. Citral, the main constituent of the essential oil in Brazilian lemongrass, was also studied for comparison. Oral doses of abafados up to 40 times (CL,,) larger than the corresponding dosage taken by humans, or of 200 mg/kg of citral, were unable to decrease body temperature of normal rats and/or rats made hyper- thermic by previous administration of pyrogen. However, both compounds acted when injected by intraperitoneal route. Oral administration of doses C 20 -CloO of abafados and 200 mg/kg of citral did not change the intestinal transit of a charcoal meal in mice, nor did it decrease the defecation scores of rats in an open-field arena. Again, by intraperitoneal route both com- pounds were active. The possible central nervous system depressant effect of the abafados was investigated by using batteries of 12 tests designed to detect general depressant, hypnotic, neuroleptic, anticonvulsant and anxio- lytic effects. In all the tests employed, oral doses of abafados up to C,,, or of citral up to 200 mg/kg were without effect. Only in a few instances did

*This work was aided by Central de Medicamentos (CEME) and AssociacZo Fundo de Incentive I Psicofarmacologia (AFIP).

0378-8741/86/$10.15 o 1986 Elsevier Scientific Publishers Ireland Ltd. Published and Printed in Ireland

38

intraperitoneal doses demonstrate effects. These data do no lend support to the popular oral therapeutic use of lemongrass to treat nervous and intestinal ailments and feverish conditions.

Introduction

Cy~~o~ogo~ citrutus Stapf. (family Gramineae), lemongrass in English, popularly known in Brazil as capim-cidr&o or cupim-sunto, is widely em- ployed in Brazilian folk medicine, Prepared as a tea or abafado, it is fre- quently used as a sedative (calmative) and hypnotic, but also as an anal- gesic, anti-emetic, antispasmodic and to treat other stomach and intestinal ailments (van den Berg, 1980; Matos et al., 1982; Nogueira, 1983; Paviani, 1964).

The medicinal use of lemongrass is not restricted to Brazil. On Mauritius Island and on the Malay Peninsula it is recommended against the common cold, pneumonia, fever and gastric problems (Fook, 1980); in Nigeria as an antipyretic and for its stimulant and antispasmodic effects (Olaniyi et al., 1975); in Angola and India it is considered as an antitussigen, anti-emetic, antiseptic and antirheumatic (Alves et al., 1960); in Indonesia it is employed to help digestion and as a diuretic and sudorific (Hirschhorn, 1983).

Substances extracted from lemongrass are also used in medicine. In India its essential oil is used to treat gastrointestinal problems (Alves et al., 1960) and geraniol, one of the constituents of the essential oil, is prescribed as an asthmolytic in China (Peigen, 1983).

The concentration of the essential oil fraction obtained from lemongrass varies from 0.2% up to 3% of the fresh plant (Alves et al., 1960); a sample from South Brazil yielded 0.28% of essential oil (Silva and Bauer, 1971). The essential oil fraction is composed of many compounds: alcohols, aldehydes, ketones, acids, esters and other terpenes and sesquiterpenes. In the essential oil obtained from the plant grown in the Phillipines, Somalia, India, Ceylon, Angola and Congo, the main component is citral (a mixture of neral and geranial) which constitutes 30--80% of the oil fraction (Abegaz and Yohannes, 1983; Oliveros-Belardo and Aureus, 1980; Rabha et al., 1980; Sylva, 1980; Vale, 1964); in the Ethiopian essential oil geraniol is the main constituent (Abegaz and Yohannes, 1983). In two samples of essential oil obtained from lemongrass of South (Rio Grande do Sul State) and South- east (Sdo Paulo State) Brazil, citral was present as the main component (86% and 48%) (Silva and Bauer, 1971; Liberalli et al., 1946).

Despite the ubiquitous medicinal use of lemongrass there is a great paucity of pharmacological research on the plant. A survey of Biological Abstracts from 1954 to 1983, revealed only two articles, one dealing with the sedative effects of the essential oil from Cymbopogon nardus (Kokate et al., 1972) and the other describing the anti-asthmatic properties of a component of Cym~opogo~ distuns (Huang et al., 1976). Similarly, a survey of the Cumu-

39

luted Index Medicus from 1960 to 1982 disclosed only two references on an antispasmodic principle present in Cymbopogon proximus (Abdel-Moneim et al., 1969; Radwan, 1975).

The present paper deals with the pharmacological effects of the tea of Cymbopogon citratus on laboratory animals. For comparison purposes citral was also used. It was decided to investigate the popular preparation (abafado) rather than chemical entities obtained from C~mbopogon citrates in an attempt to directly confirm the folk medicinal use of the plant.

To obtain data aiming to confirm the traditional therapeutic use in gastro- intestinal ailments, experiments on charcoal intestinal transit in mice anr defecation of rats in an open-field apparatus were performed. To study the eventual antipyretic properties of lemongrass, the body temperature of rats was measured. To evaluate the possible depressant effect on the central nervous system the following experiments were carried out: measurements of spontaneous motor activity in mice, grooming and rearing of rats in the open-field and rota-rod performance of mice, were used to given an indica- tion of general depressant activity; measurements of the sleep-wakefulness cycle of rats (electroencephaphalography) and potentialization of barbitu- rate sleeping-time of mice were used to study hypnotic activity; measure- ments of catatonic behavior and palpebral ptosis of rats and blockade of stereotyped behavior induced by apomorphine in rats were carried out to assess eventual neuroleptic effect; meas~ements of neophobia reaction and punished responses in rats were used to check a possible anxiolytic effect; and, finally, measurements of electroshock- and pentylenetetrazol- induced convulsions were made to assess any anticonvulsant effect.

Materials and methods

Plant material Samples of C~mbopogon citratus Stapf. from the state of CearL (North-

east Brazil), Srj,o Paul0 (Southeast Brazil) and Minas Gerais (Southeast) were harvested from July to November. The specimens were classified by bot- anists from the local universities.

The essential oil fraction of lemongrasses from Sao Paulo and Ceari revealed 46.6% and 70.9% citral and 36.7% and 16.0% myrcene, respectively (Matos et al., 1984, and unpublished data). The citral from the Cear& sample was composed of 44.2% neral and 55.8% geranial; that of Sio Paulo had 48% and 52%, respectively (Matos et al., 1984).

The doses administered to mice and rats were based on the amounts ingested by human beings. In Brazil the abafados are usually prepared from two fresh leaves finely minced with scissors or from 2 g of dried material, with 150 ml of tap water. This corresponds to about 2.0 ml abafado/kg body wt. Leaves were dried in an oven at 37-40C for 3 days resulting in a water loss of 67-78%.

For administration to mice an abu~udo I was prepared by pouring 150 ml

40

of boiling water over 2 fresh minced leaves or 2 g of powdered dried leaves; the container was covered with aluminum foil and wrapped with a piece of cloth until reaching room temperature and then filtered. In a few experiments the leaves or the powder were left in boiling water for 5 min and then covered with the aluminum foil and cloth until reaching room temperature and then filtered (abafudo II).

Dosing mice with 2.0 ml/kg of either abafado (dosage C,) was considered equivalent to the amount taken by humans. Dosages Cl0 (20 ml/kg) and CZO (40 ml/kg) corresponded to, respectively, 10 and 20 times the human dosage. For larger doses the abafados were prepared from 10 leaves or 10 g of powder to 150 ml of water. Administering 20 and 40 ml/kg corresponded to dosages C& and C,,,O, respectively. For still larger dosages the desired amount of abafudo I was taken to a lyophylizer and the residue resuspended in small volumes of water (ubufudo III).

For dosing rats, only ubufudos from 10 leaves or 10 g of powder were used; the volumes employed varied from 0.4 ml/kg (dosage C,) to 8 ml/kg (dosage &o).

Animals Male albino Swiss mice, 2-3 months old from our own colony were used.

They were kept in air conditioned laboratories at a temperature of 24 + 2C and in a 12-h dark-light cycle. Male Wistar rats, 3-4 months old from our own colony and reared in conditions similar to the mice, were also employed.

Drugs Citral (45% neral and 55% geranial) was kindly provided by Industria

Saccoman Ltda., Sao Paulo-Brazil, to whom we are grateful. The compound was solubilized with Tween-80 in distilled water (0.5% mixture of water + Tween80). Apomorphine hydrochloride (Merck Laboratories, U.S.A.) solu- tions, freshly prepared in distilled water containing 1 mg/ml of ascorbic acid was used in the stereotypy experiments. Activated charcoal (Merck Labora- tories, U.S.A.), 10 g suspended in 100 ml of 5% gum acacia was employed to study intestinal transit. Lipopolysaccharide from Escherichiu coli (Sigma Chem. Co. U.S.A.) solubilized in water, was used as pyrogenic agent. Halo- peridol (Haldol@, Johnson & Johnson Laboratories, U.S.A.), diphenylhydan- toin sodium Parke Davis Ltd. U.S.A.) and pentylenetetrazol (Sigma Chem. Co.) were the other drugs employed. Water was used as the control vehicle in the experiments with the ubufudos. Tween-80 in water (0.5%) was the control solution in the experiments with citral.

Pharmacological methods The following tests were performed on rats and mice.

Body temperature in ruts Groups of six rats each were given (orally or intraperitoneally) either

vehicle, doses Cl0 to CGO of abafados I, II and III of lemongrass from Sdo Paulo and CearS or 100 and 200 mg/kg of citral. The colonic temperature, measured by inserting the sensor probe of a digital thermometer 5-6 cm into the colon was recorded before drug treatment (time 0) and 1, 2, 3 and 4 h after drug administration.

In a second experiment, groups of six rats each were previously injected with 10 mg/kg of the pyrogen agent from E. coti, Two hours later when the rats temperature was beginning to rise, abafudos were given to the animals orally and the temperature was again recorded 1, 2 and 4 h later.

Intestinal transit in mice Twenty-four-hour fasted mice, in groups of 10 animals each, received

either vehicle, abilfudo I or citral through oral or i.p. routes. Thirty or 60 min later (see Table 2) they were given orally 0.35 ml of an aqueous suspension of 10% charcoal in 5% gum acacia (Turner, 1965). Fifteen minutes later the animals were killed by cervical dislocation and the small intestines removed. The distance the charcoal had transited from the pylorus was measured and expressed as the percentage of the total length of the small intestines.

Open-field behavior The open field consisted of a white painted arena of plywood measuring

48 X 28 X 20 cm in diameter with three 60 W lamps and three loudspeakers producing a constant noise of 76 decibels. The floor of the arena was divided into several units by black painted lines (for details see Masur, 1972).

Groups of eight rats each were treated with several abafudos from Sao Paulo lemongrass or with citral. One hour after oral administration or 30 min after i.p. injection each rat was placed in the center of the arena and defeca- tion (number of fecal boluses eliminated), ambulation (number of floor units entered) and rearing (number of times the rat stood up) were recorded for 3 min.

Rota-rod test Groups of 10 previously selected mice received various doses of abafados

or citral either by oral or intraperitoneal routes, as can be seen in Table 4. The apparatus consisted of a bar, with a diameter of 2.5 cm subdivided into five compartments by disks 25 cm in diameter (Dunham and Miya, 1957). The bar rotated at a constant speed of 12 rev./min. Pre-selection of animals was done on the experiments day by eliminating those mice which did not remain on the bar for two consecutive periods of 1 min.

One hour after the drug administration the animals were retested and the time they remained on the rotating bar, with a maximum of 60 s, were recorded.

Span tuneous motor activity Abafado I made from dried leaves from Sso Paul0 and Ceari was used.

42

Abafado III from SBo Paulo was also studied. Vehicle and citral groups were included for comparison purposes. For each dose and drug 10 mice were employed. Spontaneous motor activity was recorded by means of 10 identi- cal photocell cages, each measuring 25 X 40 X 25 cm and crossed by three light-beams.

The mice were placed individu~ly in the cages 5 min after i.p. or 30 min after oral drug administration, and the number of light-beam interruptions was recorded for the next 30 min.

Barbiturate sleeping-tide Groups of 10 mice each were administered orally or i.p. either with

vehicle (water), doses from CsO to C 208 of abafados I, II and III prepared from dried leaves from Sao Paulo, Minas Gerais and Ceara or with 100 mg/ kg of citral. Thirty minutes later the animals pretreated with the abafados or with citral received, respectively, 50 or 40 mg/kg of sodium pentob~bit~ intraperitoneally. After the barbiturate injection the sleeping-time (time interval between loss and recuperation of the righting reflex) was recorded in minutes. The criterion for recuperation of the righting reflex was fixed such that the animals had to regain their normal posture three consecutive times.

Electroencephalographic studies (EEG) Eight rats, after anesthesia with 200 mg/kg of methyleugenol (Carlini et

al., 1981), were stereotaxically implanted with bipolar stainless steel elec- trodes (200 pm diameter) onto the surface of the frontal cortices and into the posterior neck muscles. The electrodes were connected with pins to an Amphenol@ strip connector permanently attached to the skull with dental acrylic (Monti and Carlini, 1979). Following surgery, the rats were housed individually in plexiglass cages with food and water ad libitum, ambient temperature 24 ?r 2C. Two weeks were allowed for recovery from surgery.

The animals were submitted to two experimental sessions, 9 days apart, one with water and the other with dose Cl0 of abafado I obtained from dried leaves from SCo Paulo, both by oral route. Each experimenta day the rats were introduced into the experimental chamber 8 h before the experiment for adaptation to the recording situation and were connected to a Beckman polygraph.

The drugs were administered at 16 : 30 h and continuous EEG tracings were recorded for the following 12 h, that is, for 80% of the night period.

The tracings were analysed by visual inspection to obtain the following parameters: latencies to the first episode and total time spent in slow wave sleep (SWS); and latency for first episode, total number of episodes and total time spent in rapid eye movement sleep (REM). The tracings were then divided in 6 portions of 2 h each to calculate in each portion the time spent in total sleep (SWS + REM), in SWS and in REM sleep.

43

Catatonia and palpebral ptosis Groups of 8 male rats each received either through oral or i.p. routes,

vehicle, doses Cl,, and CzO of abafado from dried leaves from Sao Paulo or 20 and 100 mg/kg citral. An extra group of 5 rats was treated with 1 mg/kg of haloperidol for comparison purposes.

To measure catatonia reaction the rats were gently forced to assume an upright posture with their forepaws resting on a horizontal glass rod located 10 cm above the floor. The measures were performed beginning 1 and 2 h after drug administration and each time the animals were put in that position 3 times.

The total amount of time the rats remained with the forepaws on the rod (in the upright position) was recorded in seconds using stopwatches.

Palpebral ptosis were recorded as grades on a scale of 0 to 4 as follows: grade 0, eyes totally open; grade 1, eyes 213 open; grade 2, eyes l/2 open; grade 3, eyes l/3 open and grade 4, eyes totally closed. The grades of ptosis were recorded 1 and 2 h after drug administration, immediately before the beginning of catatonia measures.

Blockade of stereotyped behavior induced by apomorphine Groups of 8 rats each were treated orally with vehicle or doses Cl0 and

CzO of abafado I from dried leaves from Sao Paulo or intraperitoneally with 100 mg/kg of citral. Two other groups of 6 rats each received 1.0 mg/kg of haloperidol, oral or i.p. routes, for comparison purposes.

Thirty minutes later the rats were injected i.p. with 5.0 mg/kg of apomor- phine and introduced individually in wire cages measuring 30 X 20 X 15 cm with a wire distance of 2 cm. Latency for the appearance of the first sign of stereotyped behavior (sniffing, licking or biting), total time of stereotypy (time elapsed from the beginning until the animal displayed tine first groom- ing) and the grade of stereotypy were scored. The grades varied from 0 (none) to 7 (continuous biting of one wire of the cage without ambulation). For further details see Troncone et al. (1986).

Transcorneal electroshock Groups of 10 mice each received vehicle, abafados I and II from dried

leaves from Slo Paulo and Ceari or 50 and 100 mg/kg of citral. An extra group of 6 mice were dosed with 5.0 mg/kg of diphenylhydantoin for comparison purposes. Thirty minutes after drug administration the mice received a transcorneal electroshock of 8 mA and 0.2 s duration. The number of animals showing tonic convulsions and number of deaths were recorded. For the test the recommendations of Swinyard et al. (1952) were observed.

Pentylenetetrazol-induced convulsions Groups of 10 mice each were previously administered vehicle, abafados I

from fresh or dried leaves from Sao Paulo or citral. Thirty minutes later the

animals received 100 mg/kg of pentylene~trazol subcutaneously in the back of the neck. Each animal was covered by an inverted 2-l capacity beaker. The number of animals showing clonic convulsions, tonic convulsions and the number of deaths were recorded.

Neophobia reaction of rats Groups of 6 rats each were orally dosed with vehicle, CZO of abafado I

from dried leaves of lemongrass from Slo Paulo or 5.0 mg/kg of diazepam. One hour after drug admjnistration the rats were removed from the animal facilities, where they were kept 6 to a wooden cage, and were indi~du~ly introduced into metal pails of 20-l capacity (novel environment) containing a previously weighed candy of sweetened milk (novel food). Fifteen, 30, 60 and 90 min later the candies were weighed again in order to determine food consumption. For further details on the method see Silveira Filho and Tufik, (1981).

Punished response test Rats deprived of water for 48 h were individually introduced in an acrylic-

walled box (30 X 15 X 30 cm) provided with a drinking tube and a grid floor. The number of licks was recorded for 10 min. The day after this first session, a sound of 8 s duration was introduced at a variable interval, signalizing that during the final 5 s of each sound period electrical shocks of 0.1 s duration and 0.4 mA could be delivered to the tongue at each lick (punished respon- ses). The procedure was repeated until stable baselines were obtained, i.e. the rats licked much during the periods without sound and very little during the sound.

Three groups of 6 previously trained animals each received, respectively, water as vehicle, dose CZO of abafado I from Sao Paulo and 3.0 mg/kg of diaze?sm. Fifteen minutes later they were introduced into the box and the number of punished responses was recorded for 10 min.

One week later the group of rats which had received abafado I were again tested, this time after being orally dosed with a dose C,, of abafado III obtained from lemongrass of the same origin.

Results

Body temperature of rats Table 1 summarizes the results. A dose CZo of abafado I prepared from

dried leaves of lemongrass from S&o Paulo reduced body temperature by 1C {lines 1 and 2 of Table 1) 1 and 2 h after administration. However, perhaps due to the small number of animals used (6 per group) and the large standard deviations after the drug, this difference did not reach statistical significance. A bafado II from the same plant produced practically identical results (see line 4 of Table 1). However, the abafudo I from Ceara and the abafado III from Sao Paula (prepared by lyophylizing abafado I and resuspending the residue in water) were inactive (lines 3 and 5).

TA

BLE

7

EFF

EC

TS

OF

AB

AFA

DO

S I,

II, III

FRO

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FRESH

A

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OF

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ASS

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D

OF

CIT

RA

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TEM

PER

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RE

OF

RA

TS

Six

anim

als

per

dose

.

Nate

rial

Sourc

e

Pre

para

tion

Dose

R

oute

Tem

pera

ture

(C

+ S

.D.)

befo

re a

nd a

fter

dru

g a

dm

inis

trati

on

Oh

lh

2h

4h

Wate

r -

-

Dri

ed leave

s Sio

Paulo

A

bafa

do

I D

ried leave

s C

eari

A

bafa

do

I D

ried leave

s Slo

Paulo

A

baf

ado

II

Dri

ed l

eave

s Sio

Paulo

A

bafa

do

III

Wate

r -

Fresh

leave

s S&

o P

aulo

D

ried leave

s SIo

Paulo

Wate

r -

Cit

ral

- C

itra

l -

Cit

ral

---

- Aba

fado

I

A b

afad

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- - -

8 m

l/kg

C

I: 0

C 2

* C

*o

C .o

8 m

l/kg

c

20

C

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2 m

l/kg

2

00

mg/k

g

10

0 m

g/k

g

20

0 m

g/k

g

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l ora

l ora

l

i.p.

i.p.

i.p.

i.p.

orat

i.p

. i.p

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38

.1 t

0.4

4

38

.2 +

_ 0.1

9

38

.0 r

0.2

9

38

.4 t

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3

37

.5 ?

r 0.2

6

37

.9 r

0.4

8

38

.2 *

0.4

7

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.2 i

: 0

.25

38

.3 r

0.2

6

37

.7 t

0.2

9

37

.1 i

0

.24

3

7.8

* 0

.19

37

.7 t

0.2

7

36

.7 t

I.3

8

37

.9 +

0.3

8

36

.8 5

1.3

8

37

.5 t

0.2

3

37

.5 f

0.1

8

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.2 L

0.4

8

36

.8 ?

: 0.4

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.6 t

0.4

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.9 r

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.1 t

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0

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.2 c

0.2

6*

37

.6 f

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0.1

7

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.6 t

1.5

0

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.9 t

1.6

3

37

.7 ?

: 0.1

4

37

.7 t

0.2

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36

.7 +

1.3

7

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.3 *

0.4

2

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.8 f

0.2

8

37

.0 f

0.2

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37

.4 c

0.4

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37

.7 f

0.3

6

36

.2 i

0.6

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38

.0 +

_ 0.2

6

35

.8 +

0.7

9*

37

.5 +

0.2

5

37

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6

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0.2

2

36

.9 t

0.8

3

37

.3 5

0.3

6

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.8 r

0.7

4

37

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*Diffe

rs

signific

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om

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46

On the other hand, when doses CzO of u~u~~dos I obtained either from fresh or dried leaves of lemongrass from Sdo Paulo were given through intraperitoneal route, a statistically significant decrease in temperature was obtained 2 h after the injections (lines 7 and 8).

Citral (200 mg/kg) by oral route and 100 mg/kg i.p. did not significantly affect the temperature; only 200 mg/kg i.p. was effective in doing so in the first 2 h after administration (last 4 lines of Table 1).

Finally, the ~~u~~do I obtained from the dried feaves of Sgo Paulo was unable to counteract the fever induced in the rats by the pyrogen of E. co& Thus, 1 and 2 h after orally administering a dose C&, (or 4 h after the injec- tion of 10 mg/kg of the pyrogen), the temperature of the rats were 38.7 + 0.48C and 38.3 + 0.2OC, respectively. These results did not differ from the values of the control group, 38.1 + 0.37 and 38.5 f 0.35, respectively, 1 and 2 h after vehicle.

~nt~sti~a~ transit According to the first 6 lines of Table 2, oral doses CsO and Ctoo of

abafudo I obtained from fresh or dried leaves of Iemongrass from Sgo Paulo did not alter the intestinal activity of mice. Thus, the charcoal meal travelled from 55% to 73% of total small intestines whether the previous treatment had been water or any of the abafados. However, doses CloO of the abafudos from Stjo Paulo and CearG administered intraperitoneally (lines 7 and 8 of Table 2) drastically reduced in~stin~ transit. Similar results were obtained with citral. Through the oral route, 100 and 200 mgfkg did not modify the intestinal activity (lines 9-11) although the same doses when administered intraperitoneally, produced a clear reduction in intestinal transit (last 4 lines of Table 2).

Open-field behavior As can be seen in the first three lines of Table 3, oral doses CzO of abafado

I slightly reduced defecation but the difference did not reach statistical significance. A replication of this experiment (lines 4 -7 of Table 3) again showed the same non-significant decrease in defecation produced either by doses Czo of abafadas I and II or by intraperitoneal injection of dose Cl0 of abafado I. One hundred mg/kg of citral by oral route was also unable to significantly reduce defecation in rats. However, a marked decrease was noticed when citral was given by the intraperitoneal route.

As far as ~bulation is concerned, as seen in Table 3, none of the above treatments was effective in modifying it. Rearing was affected only by the i.p. injection of 100 mg/kg of citral.

Rota-rod Abafado I (first 7 lines of Table 4) from fresh leaves from Sao Paulo and

Minas Gerais did not alter the performance of mice on the rotating bar, when administered either by oral or i-p. routes or in doses 50 times larger

TA

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2

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Inte

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al t

ran

sit?

el

apse

d be

twee

n

dru

g an

d ch

arco

al

Wat

er

- -

30

20 m

l/k

g or

al

66.8

+

18.

8 F

resh

lea

ves

Sio

P

aul0

A

bafa

do

I 30

C

50

oral

71

.0

t 14

.0

Dri

ed l

eave

s S

lo

Pau

l0

Abo

fad

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30

C 5

0 or

al

73.0

f

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Wat

er

- F

resh

lea

ves

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ed l

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s S

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Aba

fad

o I

Aba

fad

o I

Aba

fad

o I

Aba

fad

o I

60

60

60

30

30

40 m

l/k

g C

I0

C IO

C

,O

C

I no

oral

66

.2

+ 1

2.3

oral

63

.4

* 12

.2

oral

55

.6

r 13

.2

i.p.

28.0

f-

8.

1*

i.p.

25.6

+

_ 7.

5**

Wat

er

- -

60

20 m

l/k

g or

al

66.8

f

6.8

Cit

ral

- -

60

100

mg/

kg

oral

69

.1

2 11

.2

Cit

ral

- -

60

200

mg/

kg

oral

59

.6

+ 1

9.5

Wat

er

- -

30

20 m

l/k

g i.p

. 71

.6

+ 1

9.0

Cit

ral

- -

30

25

mg/

kg

i.p.

55.8

t

23.7

C

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10

0 m

g/k

g i.p

. 21

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l -

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20

0 m

g/k

g i.p

. 18

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* 2.

9**

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