DEPRESSANT, ANTICONVULSANT AND ANTIBACTERIAL ACTIVITIES OF HIPPOCRATEA AFRICANA

Inter. J. of Phytotherapy / Vol 4 / Issue 3 / 2014 / 144-153.

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e - ISSN - 2249-7722

Print ISSN - 2249-7730

International Journal of Phytotherapy

www.phytotherapyjournal.com

DEPRESSANT, ANTICONVULSANT AND ANTIBACTERIAL

ACTIVITIES OF HIPPOCRATEA AFRICANA

*Jude E. Okokon1, Koofreh Davies

2, Bassey S. Antia

3, Patience J. Okokon

1

1Department of Pharmacology and Toxicology Faculty of Pharmacy, University of Uyo, Uyo, Nigeria.

2Department of Physiology, Faculty of Basic Medical Sciences, University of Uyo. 3Department of Chemistry, Faculty of Sciences, University of Uyo, Uyo, Nigeria.

INTRODUCTION

Hippocratea africana (Willd.) Loes.ex Engl.

(Celastraceae) syn. Loeseneriella africana (Willd.)

N.Hallis a green forest perennial climber without hairs

(glabrous), reproducing from seeds [1]. It is commonly

known as African paddle-pod. The Ibibio tribe of Nigeria

calls it Ebaenangenang. The plant is widely distributed in tropical Africa. The root of the plant is used

traditionally by the Ibibios of the Niger Delta region of

Nigeria in the treatment of various ailments such asfever,

convulsion, malaria, body pains, diabetes and diarrhea

[2]. Ethnobotanical survey revealed that decoction of the

plants root is also use as an antidote or antipoison to treat liver and inflammatory diseases such as jaundice and

hepatitis [3-5].The plant (root) has been reported by

Okokon et al [2] to possess in vivo anti-plasmodial

activity. Other biological activities include; anti-

inflammatory and analgesic [6], anti-diarrheal, antiulcer

[7], anti-diabetic and hypolipidemic activities

Corresponding Author:-Jude E. Okokon Email: [email protected]

ABSTRACT

Hippocratea africana (Willd.) Loes.ex Engl. (Celastraceae) is used locally to treat convulsion and

microbial infections. The root extract of Hippocratea africana was evaluated for depressant effect and antimicrobial

activity.Depressant activity was evaluated using open field, force swimming, tail suspension tests and

phenobarbitone-induced sleeping time. Anticonvulsant activity was testedagainst pentylenetetrazol and

aminophylline-induced convulsions. The root extract/fractions were screened for antimicrobial activity against

some typed and pure cultures of bacterial and fungal species using Plate -hole diffusion methodon Mueller Hinton agar (MHA) for bacteria and Sabouraud Dextrose Agar (SDA) for the fungi. Minimum Inhibitory Concentrations

(MICs) of active test samples were determined. The root extract decreased significantly (p


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[8], cytotoxicity against HeLa cells, anti-oxidative burst

and anti-leishmanial activities [9] and hepatoprotective

activity [10]. In this study, we report the anticonvulsant

and antibacterial activities of the root extract of

Hippocratea africana.

MATERIALS AND METHODS

Plant materials

Fresh roots of H.africana were collected in

August, 2014 at a forest in Uruan, Akwa Ibom State,

Nigeria. The plant was identified and authenticated by

Dr. Margaret Bassey, a taxonomist in the Department of

Botany, University of Uyo, Uyo. Nigeria. Herbarium

specimen was deposited atFaculty of Pharmacy

Herbarium.

Microorganisms

Typed and pure cultures of some bacterial and

fungal species were obtained from Pharmaceutical

microbiology unit of the Department of Pharmaceutics

and Pharmaceutical Technology, Faculty of Pharmacy,

University of Uyo, Uyo and maintained at 40oC on

nutrient agar plates before use.

Extraction

The root materialswere washed and shade-dried

for two weeks. The dried plants materials were further chopped into small pieces and reduced to powder. The

powdered material was soaked in 70% ethanol. The liquid

filtrate was concentrated and evaporated to dryness in

vacuo 40C using rotary evaporator. The crude ethanolic extract (10 g) was partitioned with a 50:50 mixture of

distilled water and chloroform. The aqueous fraction was

evaporated to dryness in a water bath at 60OC and the

chloroform fraction air-dried. The ethanolic extract, the

aqueous and chloroform fractions were stored at -4OC

until used.

Animals

The animals (Swiss albino mice of either sex)

that were used for these experiments were obtained from

University of Uyo animal house. The animals were

housed in standard cages and were maintained on a

standard pelleted feed (Guinea feed) and water ad libitum.

Permission and approval for animal studies were obtained

from College of Health Sciences Animal Ethics

committee, University of Uyo.

Evaluation of Depressant activity

Open Field test

Rats were randomly divided into groups of 5 rats

each and treated as follows for 5 days before open field

test; control (normal saline, 2 ml/kg p.o.), imipramine

(5.0 mg/kg, p.o.) and ethanolic root extract of

Hippocratea africana (200, 400 and 600 mg/kg, p.o.).

The open-field arena was made of acrylic (transparent

walls and black floor, 30 30 15 cm), divided into nine

squares of equal areas. The open field was used to

evaluate the exploratory activity of the animal [11]. The

observed parameters were the number of squares crossed

(with the four paws) and number of grooming and rearing,

recorded for 5 min testing period.

Forced Swimming test

Mice were randomly divided into groups of 5

mice each and treated as follows for 5 days before the

behavioural test; control (normal saline, 2 ml/kg p.o.),

imipramine (5.0 mg/kg, p.o.) and ethanolic root extract of

Hippocratea africana (200, 400 and 600 mg/kg, p.o.). For

assessing antidepressant activities, we employed the

method described by Porsolt et al [12,13]. The

development of immobility when mice were placed inside

an inescapable cylinder filled with water reflects the

cessation of persistent escape-directed behavior. Briefly,

mice were individually placed in a circular tank (46 cm

tall 20 cm in diameter) filled with tap water (25 1C)

to a depth of 20 cm and left there for 5 min. During this

period, the behavior of the animals was recorded by an

observer. Mice were considered immobile when remained

floating without struggling and making only slight

movements necessary to maintain the head above the

water.

Tail Suspension test (TST)

Mice of either sex were randomly divided into

groups of 5 mice each and treated as follows for 5 days

before open field test; control (normal saline, 2 ml/kg

p.o.), imipramine (5.0 mg/kg, p.o.) and ethanolic root

extract of Hippocratea africana (200, 400 and 600 mg/kg,

p.o.). The total duration of immobility induced by tail

suspension was measured according to the methods

described by Steru et al [14]. Briefly, mice both

acoustically and visually isolated were suspended 50 cm

above the floor by adhesive tape placed approximately

1 cm from the tip of the tail. Immobility time was

recorded during a 6 min period. Mice were considered

immobile only when they hung passively and were

motionless.

Anticonvulsant activity

Pentylenetetrazol induced Convulsion

Anticonvulsant effect of the extract was assessed

using a modified method of Vellucci and Webster [15] on

overnight fasted mice. The mice were divided into seven

groups of six animals each and treated with 200, 400 and

600 mg/kg of the root extract, 400 mg/kg of chloroform

and aqueous respectively, phenytoin, 40 mg/kg one hour

before induction of convulsion. Seizure was induced in

each set of mice with PTZ (70 mg/kg i.p). Control group

received normal saline. The onset of Clonic/tonic

convulsion and the mortality rate was recorded and

compared with the respective control group. The ability of


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the plant extract to prevent or delay the onset of the hind

limb extension exhibited by the animals was taken as an

indication of anticonvulsant activity [16].

Aminophylline-induced Convulsion

The extract and fractions were evaluated for

aminophylline induced convulsion using the method of Juliet et al [17].The mice were divided into seven groups

of six animals each and treated with 200, 400 and 600

mg/kg of the extract 400 mg/kg of chloroform and

aqueous respectively, phenytoin, 40 mg/kg one hour

before induction of convulsion. Seizure was induced

using aminophylline (280 mg/kg,i.p). The animals were

observed for 120 mins after the administration of AMPH

and the following parameters were noted:

1. Time to onset of myoclonic jerks in mins. 2. Time to onset of tonic convulsions in mins. 3. Time to death during experimental time of 120 mins. 4. Number of mice dead/alive at 24 hours.

Effect on phenobarbitone induced sleeping time of rats

The crude ethanolic extract was evaluated for

effect on phenobarbitone sodium sleeping time of rats.

The rats were divided into five groups of five rats each

(n=5). The extract (200, 400 and 600 mg/kg) was

administered to various groups of rats, diazepam (2

mg/kg) was given to the reference group and the control

group was given distilled water (10 ml/kg). After 30 min

the groups were treated with phenobarbitone sodium (40

mg/kg,i.p). The onset and the duration of sleep were noted

and recorded in minutes.

Evaluation of antibacterial and antifungal activities of

the extract

Plate-hole diffusion test

The evaluation of antimicrobial activity of the

extract/fractions were carried out by the Plate -hole

diffusion method [18] on Mueller Hinton agar (MHA) for bacteria and Sabouraud Dextrose Agar (SDA) for the

fungi. Solutions of the extract and fractions were prepared

in 10% Tween 80 to concentrations of 100, 50, 25 and

12.5mg/ml.

The innocula of the microorganisms were

prepared separately from 12h broth cultures (Mueller-

Hinton broth for bacteria and the Sabouraud dextrose

broth for the fungi) and incubated at 37C. All culture

media and distilled water were sterilized at 121C for 15 min in an autoclave. These innocula were diluted with

sterilized distilled water to obtain a density corresponding

approximately to 0.5 of McFarland standard turbidity

scale (108 colony forming unit CFU per ml for the

bacteria and 103 spores per ml for fungi)[18]. 0.5 ml of

each innoculum was introduced into the corresponding

fluid agar medium homogenized and 25 ml of it poured

into sterile plastic petridishes. The petridishes were

allowed on the flat slab top for the medium to solidify

within 30 min. A standard cork borer of 5mm in diameter

was used to cut four equidistant uniform wells per plate

on the surface of different plates into which was added

50l solution of each extract/fraction at varying concentration 12.5, 25, 50 and 100 mg/ml. The reference

drugs were Gentamicin, batch 20070402 (0.4 mg/ml) and

Nystatin batch 04D05 (500 g/ml). The plates were

incubated at 37C for 24 and 48h for the bacteria and fungi respectively. The antimicrobial activity was

evaluated by measuring the zone of inhibition around the

hole. Each test concentration had three replications. The

results were recorded as the mean diameter of the zones

of growth inhibition surrounding the discs [19].

Determination of minimum inhibitory concentrations

(MIC) using macrodilution method

The Minimum Inhibitory Concentrations (MICs)

of test samples found to be active by the diffusion test

were determined based on the macrodilution method [18]

with some modifications as follows. The test

extract/fractions were dissolved in 10% Tween 80 to give

a stock concentration of 100mg/ml and serially diluted

(two-fold) in a seres of test tubes to a working

concentration ranging from 1.560 to 100mg/ml using

nutrient broth supplemented with 10% glucose and 0.05%

phenol red (colour indicator). These were later inoculated

with 0.2ml suspension of the test organisms. Microbial

growth was determined by observing for color change in

the tube (red to yellow when there is growth). The lowest

concentration that showed no change of color was

considered as the MIC.

Statistical Analysis and Data Evaluation

Data obtained from this work were analyzed

statistically using one way ANOVA followed by a post

test (Turkey-Kramer multiple comparison test).

Differences between means was considered significant at

1% and 5% level of significance, that is P 0.01and 0.05

RESULTS

Open field test

Administration of root extract of H. africana

(200 600 mg/kg) for 5 days caused significant (p


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no effect on the locomotor activity of the rats. The

standard drug, imipramine (5 mg/kg), produced a

significant (p


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Table 2. Anticonvulsant Activity of Hippocratea africana root extract on PTZ- induced convulsion

Data are represented as mean SEM .significant at aP < 0.05;bp


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Table 5. Minimum inhibitory concentration of ethanolic crude root extract and fractions of H. africana (mg/ml).

Organism Crude Extract/ Fraction

Ethanolic Crude Extract Aqueous Chloroform

Staph. aureus NCTC 6571 10 6.5 3.125

Bacillus subtilis NCTC 8853 30 7.0 3.125

Pseudomonas aureginosa ATCC 27853 - 30 -

Figure 1. Bar diagram showing the effect of Hippocratea

africana root extract on line crossing frequency of rat

Results are represented as mean SEM with n = 5 in each group. *p


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Effect of the crude extract and fractions of H. Africana

on some microorganisms

Table 4 shows the diameters of the zones of

inhibition exhibited by ethanolic crude extract and

fractions at various concentrations employed. The crude

extract, chloroform and aqueous fractions showed a

narrow spectrum of activity against gram positive Staph

aureus (NCTC 6571) and Bacillus subtilis (NCTC 8853).

Pseudomonas aeroginosa (ATCC 27853) was the only

gram negative bacteria tested that was sensitive to the

aqueous fraction. The chloroform fraction had the highest

activity against both Staph aureus and Bacillus subtilis

followed by aqueous fraction and the crude extract. Other

tested organisms were not sensitive to either the crude

extract or fractions..The activities of the crude

extract/fractions were not comparable to that of the

standard, streptomycin. The crude extract and the

fractions were inactive against all fungal species tested.

The results of minimum inhibitory concentrations

(MIC)of the crude / fraction are shown in Table 5. The

lowest MICs of chloroform fraction (3.125 mg/ml) were

recorded against B.subtilis (NCTC 8853) and Staph.

Aureus (NCTC 6571). While the MICs of aqueous

fraction against B. subtilis and Staph aureus were 7.0 and

6.5 mg/ml respectively. Aqueous fraction also inhibited P.

aeruginosa with MIC value of 30.0 mg/ml.

DISCUSSION

In this study, evaluation of the effect of ethanolic

root extract on central nervous system was carried out in

rats using different models; Open field test, tail

suspension test and force swimming test. The root extract

(200 600 mg/kg) was found to cause significant dose dependent reductions in the frequency of line crossing and

rearing activities of the pretreated rats, while the walling

frequency was significantly (p


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delay the onset of tonic/clonic convulsions and prolonged

the time of the death of the treated mice against

pentylenetetrazol and aminophylline induced convulsions.

The aqueous fraction was observed to have the highest

activity.

The exact mechanisms of seizures induced by

aminophylline appear to be diverse, multiple and

complex, and also unclear. Evidence suggests that

seizures induced by aminophylline, could be the result of

adenosine receptor antagonism or due to inhibition of

cerebral nucleotidase activity [30, 31], which lower the

adenosine content in the brain and eventually lead to a

process of disinhibition. However, report has it that di-

phenylhydantoin a potent inhibitor of adenosine uptake

was ineffective in preventing these seizures [32]. Apart

from non-specific adenosine receptor antagonism [33],

aminophylline is thought to have inhibitory influence on

adenosine synthesis. At higher doses inhibition of

phosphodiesterase activity including mobilization of

intracellular calcium ions from labile stores are said to be

implicated in AMPH-induced seizures [34, 35]. However,

a report by Ray et al., [36], has implicated oxidative stress

due to the generation of free radicals and reactive oxygen

species to be responsible for the seizures induced by

aminophylline.

Hippocratea africana root extract and fraction

which was observed to delay the onset of aminophylline

induced convulsion, has been reported to contain -thujene , sabinene and sesquiterpenes, which have been

implicated in the anticonvulsant activities of plants

[37,38]. These compounds may be responsible for the

observed anticonvulsant activity of the plant. Also,

Okokon et al. [10] reported the antioxidative property of

the root extract. The antioxidant activity of this root

extract may be responsible for the observed protection

against aminophylline induced convulsion.

According to De Sarro et al.,[39],

pentylenetetrazol (PTZ)is suggested to exert its

anticonvulsant effect by inhibiting the activity of gamma

aminobutyric acid (GABA) at GABAA receptors. Gamma

aminobutyric acid is the major inhibitory neurotransmitter

which is implicated in epilepsy. The enhancement and

inhibition of the neurotransmission of GABA will

attenuate and enhance convulsion respectively [40,41].

Phenobarbitone and diazepam, standard epileptic

drugs,have been shown to exert their antiepileptic effects

by enhancing GABA-mediated inhibition in the brain

[42,43]. These drugs are reported to antagonise PTZ-

induced convulsion [44] by enhancing GABA

neurotransmission. Phenytoin was unable to prevent PTZ-

induced seizure because it is thought to exert its

antiepileptic effect by blocking sodium ions into brain

cells thus inhibiting generation of repitative action

potential [42]. Since the root extract and fractions of

Hippocratea africana were able to delay PTZ induced convulsion it is probable that they may be interfering with

gabaergic mechanism(s) to exert its effect. Their

anticonvulsant activities are due to their phytochemical

components as reported above.

The ethanol root extract of H. africana was

found to significantly enhanced duration of the

phenobarbitone sodium -induced hypnotic effect, which

was observed in the shortening of time of onset of sleep

and prolonging the duration of sleep following its

administration suggesting a depressant activity on the

CNS. Substances which possess CNS depressant activity

either decrease the time for onset of sleep or prolong the

duration of sleep or both [45, 46]. A prolongation of the

phenobarbitone effect could involve a facilitation of

GABA mediated postsynaptic inhibition through

allosteric modification of GABAA receptors.

The root extract and fractions were found to

exert antibacterial activity against Gram positive S.

aureus and B. subtilis as well as Gram negative P.

aureginosa. This activity may have resulted from the

presence of phytochemical compounds such as

monoterpenes (thujene and sabinene) and sesquiterpenes

as reported above.

Compounds such as terpenes (mono and

sesquiterpenes) which have been implicated in

antibacterial activities of plants [47, 48] have been found

to be present in this extract. These compounds may have

been responsible for the antibacterial activity observed in

this study.

CONCLUSION

From the results of this study, the root extract/

fractions possess significant CNS depressant and

anticonvulsant activities as well as a considerable

antibacterial activity. It will be interesting to isolate and

characterised the active ingredient in this extract

CONFLICT OF INTEREST There is no conflict of interest.

ACKNOWLEDGEMENT The authors are grateful to Mr. Nsikan Malachy

Udo of Department of Pharmacology and Toxicology for

technical assistance.

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