CHAPTER-4 PLANT PROFILE AND EVALUATION OF …shodhganga.inflibnet.ac.in/bitstream/10603/70545/11/11_chapter 4.pdf · PLANT PROFILE AND EVALUATION OF ANTIEPILEPTIC ACTIVITY OF ACALYPHA

43

CHAPTER-4 PLANT PROFILE AND EVALUATION OF ANTIEPILEPTIC

ACTIVITY OF ACALYPHA FRUTICOSA

S. No Name of the Sub-Title Page No

4.1 Taxonomy 45-45

4.2 Distribution 45-45

4.3 Description 45-46

4.4 Chemical constituents 46-46

4.5 Traditional uses 47-47

4.6

4.7

Previous Investigations

Reason for selection

47-51

51-51

4.8 Materials and methods 51-55

4.9 Results 55-83

4.10 Discussion 84-88

44

Fig: 4.1. Acalypha fruticosa

Fig: 4.2. Acalypha fruticosa

45

4.1. Taxonomy

Kingdom : Plantae

Phylum : Magnoliophyta

Class : Magnoliopsida

Order : Euphorbiales

Family : Euphorbiaceae

Genus : Acalypha

Species : fruticosa

Synonyms : Ricinocarpus fruticosus, Acalypha betulina

Common name: Birched-leaved Acalypha.

Vernacular Names

Telugu : cinnaku, chinni, cinni, tsinnie, chinnaaku, mabbaku

Kannada : chinee mara, chinni, chinnimara, cinni.

Malayalam : perim-munja

Tamil : siru sinni, cinni, kittik-kilanku, sinni, cinniver, perun

cinni, chinni.

4.2. Distribution

Acalypha fruticosa (Euphorbiaceae) commonly known as

“Chinnichedi” and “Birch-leaved Acalypha” is a strong smelling

pubescent and bushy shrub found in India from Orissa to Karnataka,

Tamil Nadu and Kerala.

4.3. Description

Monoecious, much-branched, aromatic shrub upto 4 m tall. Stems

hairy and green first, later almost glabrous and reddish brown. Leaves

are simple and arranged spirally. Stipules are brown, 3-4 mm long

46

and narrowly lanceolate; petiole 0.5-4.5 cm long; blade broadly ovate

to rhombic ovate, 1-9 cm X 1-5 cm, base cuneate to rounded, apex is

acuminate with toothed margins, sparingly to evenly yellowish gland-

dotted beneath and membranous, 5-7 veined at base and with 2-5

pairs of lateral veins.

Inflorescence an axillary, solitary spike upto 5 cm long, the lower

part interrupted, with 1-7 female flowers, the upper part consists of

densely congested male flowers, ending with a female flower; peduncle

hairy; bracts in female flowers broadly ovate to kidney shaped, 1 cm X

1-1.5 cm, toothed, sparingly yellow gland-dotted and prominently

ribbed. Flowers are unisexual, sessile and petals are absent; male

flowers consist of 4-lobes with minute, densely white hairy calyx and 8

stamens; female flowers consist of 3 ovate-lanceolate, 1 mm long,

ciliate sepals, ovary superior, 0.5 mm in diameter, 3-celled, 3-lobed to

almost globose, densely shortly hairy, styles 3, free, 4 mm long,

fringed, pink or red.

Fruit a 3-lobed capsule 2 mm X 3 mm, yellow gland-dotted,

densely shortly hairy. Fruit is splitted into 3 cocci with 2-valves and

1-seed each. Seeds ellipsoid-ovoid, 1.5-2 mm X 1-1.5 mm, smooth,

brown, caruncle elliptical.

4.4. Chemical Constituents

Alkaloids, anthraquinones, coumarins, flavonoids, phenols,

quinones, tannins, terpenoids, saponins and steroids [102].

47

4.5. Traditional uses

In traditional system of medicine the young twigs and leaves of the

plant are prescribed in the treatment of dyspepsia, colic, diarrhoea

and in cholera. The Paliyar and Irula tribes in Western Ghats of South

India use leaves and roots of Acalypha fruticosa to treat stomachache,

skin diseases, wounds and poisonous bites [103]. In Siddha Materia

Medica it is used to treat poisonous bites. Medicinally the leaves are

used as stomachic in dyspepsia, attenuant, alterative and vulnerary

[104]. In Yemen, leaf and stem have been used to treat skin diseases,

malaria and wounds [105].

In Tanzania, a leaf decoction is drunk to treat epilepsy. Leaf

maceration is used to treat eye infections. A leaf infusion is used to

treat stomach problems and swellings of the body. Leaf sap is used as

nose drops to treat cough and chest problems. Leaf paste is applied to

scabies and sores. Stems ground in water are applied to wounds of

animals. The Suiei hunter-gatherers of northern Kenya used root

decoction to treat convulsions, colds, fever and swellings of the

scrotum. They used root infusion to treat whooping cough. They

chewed stem and root to relieve toothache. In southern Africa a root

decoction is taken to treat snakebites, fever and ulcers of venereal

origin. Ground fresh leaves mixed with water are rubbed in and

inhaled as a sedative [21].

4.6. Previous Investigations

• Mathad et al., evaluated the antidiarrhoeal activity of methanol

and aqueous extracts of Acalypha fruticosa leaves by using

48

castor oil-induced diarrhoea model in rats. They reported that

methanol and aqueous extracts decreased propulsion of the

charcoal meal (p<0.001) through the gastrointestinal tract at the

oral dose of 200mg/kg as compared with control group [106].

• Gupta et al., reported the antioxidant and anti-inflammatory

activities of the methanol extract of the leaves of Acalypha

fruticosa by DPPH radical scavenging assay and in vitro lipid

perioxdation induced by Fe2+-ascorbate system in the rat liver

homogenate, carrageenan induced paw oedema and cotton

pellet induced granuloma in rats. They reported that the extract

showed marked free radical scavenging activities in DPPH

radical scavenging assay, in vitro lipid perioxidation induced by

Fe2+-ascorbate system in the rat liver homogenate and

significant anti-inflammatory activity in carrageenan-induced

paw oedema in rats [107].

• Duraipandiyan and coworkers reported the antimicrobial

activity of the hexane and methanol extracts of Acalypha

fruticosa against some bacterial strains. They reported that the

methanol extract showed significant activity against tested

organisms when compared to hexane extract [108].

• Alshawsh and coworkers reported the antimalarial activity of

the methanol and aqueous extracts of Acalypha fruticosa leaves

against Plasmodium falciparum. They found that the extract

have significant antiplasmodial activity with IC50 values less

than 4µg/ml [109].

49

• Mothana et al., investigated the antimicrobial activity of the

methanolic and aqueous extracts of Acalypha fruticosa using

agar diffusion method. They also studied the antioxidant activity

using scavenging activity of DPPH radical method and cytotoxic

activity using the neutral red uptake assay. They reported that

the methanol extract showed antibacterial activity only against

Gram-positive bacteria, high free radical scavenging activity and

remarkable cytotoxic activity against FL-cells [110].

• Lingathurai and coworkers proved the antifeedant and

larvicidal activities of the n-hexane, chloroform and ethylacetate

extracts of Acalypha fruticosa leaves against Plutella xylostella

larvae using leaf disc no-choice method. They reported that the

chloroform extract showed maximum antifeedant activity [111].

• Gopalakrishnan and coworkers investigated the wound

healing activity of the ethanol extract of the aerial parts of

Acalypha fruticosa by excision and dead space wound models in

rats and reported that the extract showed significant wound

healing activity [112].

• Sivakumar et al., reported the anti-tumor activity of the

methanol extract of the leaves of Acalypha fruticosa against

Ehrlich’s Ascites Carcinoma (EAC) bearing Swiss albino mice.

They proved that the extract showed remarkable decrease in

tumor volume and viable cell count and prolonged the life span

of EAC tumor bearing mice and also significantly decreased the

lipid peroxidation while it increased the glutathione content and

50

superoxide dismutase level as compared to that of EAC control

group [113].

• Ireri and coworkers reported the insecticidal activity of the

methanol and ethyl acetate extracts of aerial parts of Acalypha

fruticosa against sandflies (Phlebotomus duboiscqi). They

reported that the extracts were found to be insecticidal to adult

sandflies [114].

• Rajkumar et al., reported the antioxidant activity of Acalypha

fruticosa by Ferric reducing antioxidant property (FRAP) assay,

radical scavenging assays (DPPH and hydroxyl) and

thiobarbituric acid (TBA) assay. They assessed the cytotoxicity

by XTT assay in MDA-MB-435S (human breast carcinoma cell

line) and Hep3B (human hepatocellular carcinoma) and DNA

protective efficiency using UV-photolysed H2O2-driven oxidative

damage to pBR322. They reported that both the extracts

exhibited promising antioxidant potentials and marginal

cytotoxicity to the tested cell lines [115].

• Sripathi and Sankari evaluated the antibacterial activity of

the ethanol extract of Acalypha fruticosa against Streptococci sp,

Escherichia coli and Proteus sp. and reported that the extract

showed moderate activity against chosen strains [116].

• Gopalakrishnan et al., identified 1, 2-Benzene dicarboxylic

acid di isooctyl ester, n-hexadecanoic acid, 9,12-octadecadienoic

acid (Z, Z), α-D-glucopyranoside and eicosyl trichlorosilane from

51

the aerial parts of Acalypha fruticosa by GC-MS analysis of the

ethanol extract [102].

• Deepa et al., isolated β–caryophyllene, α-humulene,

isocaryophyllene, caryophyllene oxide and tans-phytol from the

essential oil of Acalypha fruticosa leaves [117].

4.7. Reason for selection

Aerial parts of Acalypha fruticosa were traditionally used to treat

epilepsy [21]. But till today, there were no reports to justify its claim.

Hence the present work was designed to prepare petroleum ether,

chloroform, ethanol, aqueous extracts of Acalypha fruticosa and

evaluate the antiepileptic activity by using three models namely MES,

PTZ and INH-induced convulsions in mice.

4.8. Materials and methods

4.8.1. Drugs and Chemicals

Isoniazid (S.D. Fine-Chem. Ltd), Diazepam (Ranbaxy),

Phenobarbitone sodium (Bayer AG) and Pentylenetetrazole (Sigma

Aldrich Chemical Co.). All other chemicals used are of Merck, India

(LR grade).

4.8.2. Plant collection

The aerial parts of Acalypha fruticosa were collected from Tirupati,

Andhra Pradesh, India. The aerial parts of the plant were identified

and authenticated by Botanist, Dr. K. Madhava Chetty, Assistant

Professor, Department of Botany, Sri Venkateswara University,

Tirupati. The plant specimen was deposited at Sri Venkateswara

University Herbarium, Tirupati with voucher number 1252.

52

4.8.3. Preparation of the extracts

The fresh aerial parts of Acalypha fruticosa were collected, shade

dried and was made in to coarse powder. Then petroleum ether,

chloroform, ethanol and aqueous extracts were prepared by following

maceration method [118].

4.8.4. Preliminary Phytochemical Studies

Different extracts of plant were subjected to qualitative chemical

tests for various phytoconstituents like alkaloids, carbohydrates,

flavonoids, lipids, proteins, saponins, steroids and tannins. The

various tests and reagents used are given below [119].

Table 4.1. Preliminary Phytochemical studies

Phytoconstituents Chemical test

Alkaloids Dragendorff’s test

Carbohydrates Molisch test

Flavonoids Shinoda test

Lipids Filter paper test

Proteins Biuret test

Saponins Foam test

Steroids Liebermann-Burchard test

Tannins Ferric chloride test

4.8.5. Pharmacological Investigations

4.8.5.1. Animals

Young adult Swiss albino rats of either sex weighing (150-180 g)

and Swiss albino mice of either sex, weighing (25–30 g) were procured

from M/s Mahavir Enterprises, Hyderabad. They were housed in

standard polypropylene cages and kept under controlled room

53

temperature (24±20C; relative humidity 60-70%) in a 12h light – dark

cycle. The rats and mice were given a standard laboratory diet and

water ad libitum. The animals were acclimatizated before the study.

The experimental protocol was approved by the Institutional Animals

Ethics Committee (IAEC) of Talla Padmavathi College of Pharmacy,

Warangal, Andhra Pradesh (CPCSEA no. 1505/PO/a/11/CPCSEA).

4.8.5.2. Acute toxicity studies

Acute toxicity study was performed for the extracts to ascertain

safe dose by acute oral toxic class method of Organization of

Economic Co-operation and Development, as per 420 guidelines

(OECD). Young adult Swiss albino rats and Swiss albino mice of either

sex were used for the study. Each extract of plant was tested in both

the species upto a dose of 2000 mg/kg, body weight [120].

4.8.5.3. Evaluation of Anti-epileptic activity

4.8.5.3.1. Maximum Electroshock (MES) in mice

Five groups of six Swiss albino mice (25–30 g) of either sex were

used. Mice belonging to Group I were treated with the vehicle, Group

II, III and IV were treated with different doses (30, 100 and 300

mg/kg, p.o.) of Acalypha fruticosa respectively. Mice belonging to

Group V received diazepam (standard) at the dose of 3 mg/kg, p.o.

The test was started one hour after oral treatment with the extract or

the vehicle or the standard. Tonic hind limb extensions were induced

by an apparatus with corneal electrodes. The intensity of the stimulus

was dependent on the apparatus, eg: 45 mA, 50Hz for 0.2 sec has

54

been used. Percentage of inhibition of convulsions relative to control

was calculated [40].

Control - Treated Percentage of Inhibition = -------------------------- X 100 Control

Same treatment schedule was followed for chloroform, ethanol and

aqueous extracts.

4.8.5.3.2. Pentylenetetrazole (PTZ)-induced convulsions

Mice of either sex were randomly allotted to five different groups of

six mice each. Mice belonging to Group I received the vehicle, Group

II, III and IV received Acalypha fruticosa at the doses of 30, 100 and

300 mg/kg, p.o. respectively. Mice belonging to Group V received

phenobarbitone sodium (standard) at the dose of 40 mg/kg, i.p. Mice

belonging to Group I were administered with pentylenetetrazole (PTZ)

(75 mg/kg, i.p.) one hour after vehicle. Mice belonging to Group V

received PTZ, 15 min after phenobarbitone sodium (40 mg/kg, i.p.).

Mice belonging to Group II, III and IV mice received different doses of

plant extracts, p.o. one hour before PTZ. Onset time as well as

duration of convulsions were recorded [85].


aqueous extracts.

4.8.5.3.3. Isoniazid (INH)-induced convulsions

Five Groups of six Swiss albino mice (25–30 g) of either sex were

used. Mice belonging to Group I were treated with the vehicle, Group

II, III and IV were treated with different extracts of Acalypha fruticosa

55

at the doses of 30, 100 and 300 mg/kg, p.o. Mice belonging to Group

V received the standard drug, diazepam at the dose of 4 mg/kg, i.p.

One hour after the administration of vehicle or different extracts of

Acalypha fruticosa, isoniazid at a dose of 300mg/kg, s.c. was

administered to mice belonging to Group I, II, III, IV and 15 min after

administration of diazepam to mice belonging to Group V. The mice

were placed in isolated perplex chamber and the latency of

convulsions was recorded [121].


aqueous extracts.

4.8.6. Statistical analysis:

The data was analyzed using one-way analysis of variance

(ANOVA), followed by Dunnett’s test and p<0.05 was considered as

statistically significant. The data was expressed as mean ± Standard

deviation (SD).

4.9. Results

4.9.1. Percentage yield of different extracts of Acalypha fruticosa

After extraction with different solvents by maceration method, the

percentage yield was calculated. The percentage yield obtained for

petroleum ether extract-12.74, chloroform extract-14.55, ethanol

extract-31.99 and aqueous extract-9.96.

4.9.2. Preliminary Phytochemical Studies

Preliminary phytochemical studies gave positive tests for alkaloids,

steroids, carbohydrates, tannins, flavanoids, saponins, lipids and

proteins in various extracts of the plants.

56

Table 4.2. Preliminary Phytochemical studies of Acalypha fruticosa

Phytoconstituents PAF CAF EAF AAF

Alkaloids -ve - ve + ve + ve

Steroids + ve + ve + ve - ve

Carbohydrates - ve - ve - ve + ve

Tannins - ve - ve + ve + ve

Flavonoids - ve + ve + ve - ve

Saponins - ve - ve + ve + ve

Lipids + ve + ve + ve - ve

Proteins - ve - ve - ve + ve

4.9.3. Pharmacological Investigations

4.9.3.1. Acute toxicity studies

In the acute toxicity studies, mortality was found at 2000mg/kg,

p.o. for all the extracts. All the four extracts were found to be safe

upto 1000 mg/kg, p.o. Based on the results of the study, three doses

of different extracts i.e., 30, 100 and 300 mg/kg, p.o. were selected for

the evaluation of anti-epileptic activity.

4.9.3.2. Evaluation of Antiepileptic activity

4.9.3.2.1. Antiepileptic activity of Petroleum ether extract of

Acalypha fruticosa (PAF)

4.9.3.2.1.1. Maximal electroshock-induced convulsions in mice

The average time of onset, duration of tonic hind limb extension

(THLE) and percentages of inhibition of convulsions were presented in

Table 4.3.

57

Effect on onset time of convulsions

The onset time of THLE in control group animals was found to be

1.34±0.04 sec. PAF treated mice showed the onset time as 1.89±0.05,

2.25±0.05 and 3.04±0.08 sec (p<0.01) respectively at the doses of 30,

100 and 300 mg/kg, p.o. Animals treated with diazepam (3 mg/kg,

p.o.) showed onset time as 2.48±0.05 sec (p<0.01).

Effect on duration of convulsions

The duration of THLE in control group animals was 118.91±0.22

sec. Albino mice pretreated with PAF at the doses of 30, 100 and 300

mg/kg, p.o. showed the duration of 67.33±0.08, 58.66±0.06 and

44.79±0.14 sec (p<0.01) respectively. The standard group animals

(diazepam 3 mg/kg, p.o.) showed 49.36±0.06 sec (p<0.01).

It has been found that the time of onset of THLE in control group

animals was very less when compared to that of animals which

received extract and standard. Duration of THLE in control group

animals was greater when compared to that of animals which received

extract and standard. Albino mice pretreated with PAF at the doses of

30, 100 and 300 mg/kg were provided significant protection from

convulsions induced by electroshock method.

Percentage inhibition of convulsions

The percentage of inhibition achieved in mice pretreated with PAF

at the doses of 30, 100 and 300 mg/kg were 43.38%, 50.67% and

62.33% (p<0.01) respectively when compared to control group

animals. Animals treated with PAF exhibited significant antiepileptic

58

activity and more percentage of inhibition of convulsions at the dose of

300 mg/kg when compared to diazepam treated animals (58.49%).

Table 4.3. Effect of PAF on maximal electroshock-induced convulsions

in mice

Group

(n=6)=

6)

Treatment Onset of

THLE (sec)

Duration of

THLE (sec)

Percentage

inhibition of

convulsions

IPAM DMSO 1.34±0.04 118.91±0.22 -

IIPAM PAF (30 mg/kg) 1.89±0.05** 67.33±0.08** 43.38**

IIIPAM PAF (100 mg/kg) 2.25±0.05** 58.66±0.06** 50.67**

IVPAM PAF (300 mg/kg) 3.04±0.08** 44.79±0.14** 62.33**

VPAM Diazepam (3 mg/kg) 2.48±0.05** 49.36±0.06** 58.49**

PAF: Petroleum ether extract of Acalypha fruticosa; Values were

mean±SD (n=6). Statistical significance was determined by ANOVA,

followed by Dunnett’s t test (n=6); **p < 0.01when compared to Group

IPAM (control).

4.9.3.2.1.2. Pentylenetetrazole (PTZ)-induced convulsions in mice

The average time of onset, duration of convulsions and percentages

of inhibition of convulsions were presented in Table 4.4.


The onset time of convulsions in control group animals was

3.11±0.04 min. PAF treated mice exhibited the onset time as

3.48±0.05, 3.58±0.01 and 4.24±0.03 min (p<0.01) respectively at the

doses of 30, 100 and 300 mg/kg, p.o. The standard group mice

(Phenobarbitone sodium, 40 mg/kg, i.p.) showed 6.36±0.03 min

(p<0.01).

59


The duration of convulsions in control group animals was

22.14±0.05 min. Animals pretreated with PAF at the doses of 30, 100

and 300 mg/kg, p.o. exhibited the duration as 10.43±0.08, 8.59±0.22

and 7.42±0.10 min (p<0.01) respectively. The standard group mice

(Phenobarbitone sodium 40 mg/kg, i.p.) showed 11.13±0.05 min

(p<0.01).

The time of onset of convulsions in control group animals was very

less when compared to the animals treated with extract and standard.

Duration of convulsions in control group animals was greater when

compared to the extract and standard treated animals. It has been

found that animals pretreated with PAF were significantly protected

from convulsions induced by PTZ in a dose-dependent manner.


The percentage of inhibition achieved in PAF treated mice were

52.89%, 61.20% and 66.49% (p<0.01) respectively at the doses of 30,

100 and 300 mg/kg when compared to control group animals.

Animals which were treated with PAF exhibited significant

antiepileptic activity and more percentage inhibition of convulsions

when compared to Phenobarbitone sodium treated mice (49.73%,

p<0.01).

60

Table 4.4. Effect of PAF on Pentylenetetrazole (PTZ)-induced

convulsions in mice

Group

(n=6)=

6)

Treatment

Onset of

convulsions

(min)

Duration of

convulsions

(min)

Percentage

inhibition of

convulsions

IPAP DMSO 3.11±0.04 22.14±0.05 --

IIPAP PAF (30 mg/kg) 3.48±0.05** 10.43±0.08** 52.89**

IIIPAP PAF (100 mg/kg) 3.58±0.01** 8.59±0.22** 61.20**

IVPAP PAF (300 mg/kg) 4.24±0.03** 7.42±0.10** 66.49**

VPAP Phenobarbitone sodium

(40 mg/kg, i.p.) 6.36±0.03** 11.13±0.05** 49.73**



followed by Dunnett’s t test (n=6); **p < 0.01 when compared to Group

IPAP (control).

4.9.3.2.1.3. Isoniazid (INH)-induced convulsions in mice

The average latency of convulsions were presented in Table 4.5.

Effect on latency of convulsions

The latency of convulsions in control group animals was

25.33±0.03 min. Albino mice pretreated with PAF showed the latency

of convulsions of 29.18±0.09, 31.02±0.41 and 34.12±0.06 min

(p<0.01) respectively at the doses of 30, 100 and 300 mg/kg, p.o. The

standard group mice (diazepam 4 mg/kg, i.p.) exhibited 63.27±0.04

min (p<0.01).

The latency of convulsions in control group animals was very less

when compared to that of animals pretreated with extract and

standard. Animals treated with PAF showed the latency time more

than that of control group animals and less than that of standard

61

group animals. Although all the three doses of PAF significantly

delayed the latency of convulsions in a dose-dependent manner but

failed to protect mice against mortality.

Table 4.5. Effect of PAF on Isoniazid (INH)-induced convulsions in mice

Group (n=6) Treatment Latency of

convulsions (min)

IPAI DMSO 25.33±0.03

IIPAI PAF (30 mg/kg) 29.18±0.09**

IIIPAI PAF (100 mg/kg) 31.02±0.41**

IVPAI PAF (300 mg/kg) 34.12±0.06**

VPAI Diazepam (4 mg/kg, i.p.) 63.27±0.04**



followed by Dunnett’s t test (n=6); **p < 0.01 when compared to Group

IPAI (control).

4.9.3.2.2. Anti-epileptic activity of Chloroform extract of

Acalypha fruticosa (CAF)


The average time of onset, duration of THLE and percentages of

inhibition of convulsions were presented in Table 4.6.


The onset time of THLE in control group animals was 1.34±0.04

sec. CAF treated mice showed the onset time as 1.97±0.05, 2.57±0.06

and 3.16±0.10 sec (p<0.01) respectively at the doses of 30, 100 and

300 mg/kg, p.o. Animals which received standard i.e., diazepam (3

mg/kg, p.o.) showed 2.48±0.05 sec (p<0.01).

62



sec. Mice pretreated with CAF at the doses of 30, 100 and 300 mg/kg,

p.o. showed the duration of 62.07±0.13, 51.96±0.11 and 40.04±0.07

sec (p<0.01) respectively. The standard group mice (diazepam 3

mg/kg, p.o.) showed 49.36±0.06 sec (p<0.01).

The time of onset of THLE in control group animals was very less

when compared to the extract and standard group animals. Duration

of THLE in control group animals was greater when compared to the

extract and standard group animals. Albino mice pretreated with CAF

at doses 30, 100 and 300 mg/kg provided significant protection from



The percentage inhibition achieved in CAF treated animals were

47.80% (30 mg/kg), 56.30% (100 mg/kg) and 66.33% (300 mg/kg)

(p<0.01) respectively when compared to control group animals.

Animals pretreated with CAF exhibited significant antiepileptic activity

and more percentage inhibition of convulsions at the dose of 300

mg/kg when compared to diazepam treated animals (58.49%, p<0.01).

63

Table 4.6. Effect of CAF on maximal electroshock-induced convulsions

in mice

Group

(n=6)=

6)

Treatment Onset of

THLE (sec)

Duration of

THLE (sec)

Percentage

inhibition of

convulsions

ICAM DMSO 1.34±0.04 118.91±0.22 ---

IICAM CAF (30 mg/kg) 1.97±0.05** 62.07±0.13** 47.80**

IIICAM CAF (100 mg/kg) 2.57±0.06** 51.96±0.11** 56.30**

IVCAM CAF (300 mg/kg) 3.16±0.10** 40.04±0.07** 66.33**

VCAM Diazepam (3 mg/kg) 2.48±0.05** 49.36±0.06** 58.49**

CAF: Chloroform extract of Acalypha fruticosa; Values were mean±SD

(n=6). Statistical significance was determined by ANOVA, followed by

Dunnett’s t test (n=6); **p < 0.01 when compared to Group ICAM

(control).





The onset time of convulsions in control group animals was found

to be 3.11±0.04 min. Animals which received CAF at the doses of 30,

100 and 300 mg/kg, p.o. exhibited the onset time as 3.57±0.03,

4.22±0.05 and 4.42±0.05 min (p<0.01) respectively. Animals belonging

to standard group (Phenobarbitone sodium, 40 mg/kg, i.p.) showed

6.36±0.03 min (p<0.01).



22.14±0.05 min. CAF treated mice exhibited the duration as

64




(p<0.01).


less when compared to the extract and standard treated animals.


compared to the extract and standard treated animals. All the three

doses of CAF afforded significant protection in dose-dependent

manner against convulsions induced by PTZ.


The percentage of inhibition achieved in CAF treated mice were



Animals pretreated with CAF exhibited significant anti-epileptic

activity and more percentage of inhibition of convulsions when

compared to Phenobarbitone sodium treated animals (49.73%,

p<0.01).

65

Table 4.7. Effect of CAF on Pentylenetetrazole (PTZ)-induced

convulsions in mice

Group (n=6)=

6) Treatment

Onset of convulsions

(min)

Duration of convulsions

(min)


ICAP D DMSO MSO 3.11±0.04 22.14±0.05 ---

IICAP CAF (30 mg/kg) 3.57±0.03** 10.01±0.35** 54.79**

IIICAP CAF (100 mg/kg) 4.22±0.05** 8.02±0.22** 63.78**

IVCAP CAF (300 mg/kg) 4.42±0.05** 7.04±0.24** 68.20**

VCAP Phenobarbitone sodium

(40 mg/kg, i.p.) 6.36±0.03** 11.13±0.05** 49.73**



Dunnett’s t test (n=6); **p < 0.01 when compared to Group ICAP

(control).





25.33±0.03 min. Albino mice pretreated with CAF showed the latency


(p<0.01) respectively at the doses of 30, 100 and 300 mg/kg, p.o.

Animals belonging to standard group (diazepam 4 mg/kg, i.p.) showed

63.27±0.04 min (p<0.01). The latency of convulsions in control group

animals was very less when compared to the extract and standard

group animals. All the three doses of CAF showed the latency of

convulsions more than that of control and less than that of standard

i.e., diazepam. Although CAF delayed the latency of convulsions in a

66

dose-dependent manner, but failed to protect the mice against

mortality.

Table 4.8. Effect of CAF on Isoniazid (INH)-induced convulsions in

mice


convulsions (min)

ICAI DMSO 25.33±0.03

IICAI CAF (30 mg/kg) 29.47±0.06**

IIICAI CAF (100 mg/kg) 31.49±0.06**

IVCAI CAF (300 mg/kg) 35.01±0.22**

VCAI Diazepam (4 mg/kg, i.p.) 63.27±0.04**



Dunnett’s t test (n=6); **p < 0.01 when compared to Group ICAI

(control).

020406080

100120140

Dur

atio

n of

TH

LE

(sec

)

Treatment

DMSO

PAF 30 mg/Kg

PAF 100 mg/Kg

PAF 300 mg/Kg

CAF 30 mg/Kg

CAF 100 mg/Kg

CAF 300 mg/Kg

Diazepam 3 mg/Kg

Fig: 4.3. Effect of PAF and CAF on duration of maximal electroshock-

induced convulsions in mice. Values were mean±S.D (n=6).

67

010203040506070

Perc

enta

ge in

hibi

tion

of

conv

ulsio

ns

Treatment

PAF 30 mg/Kg

PAF 100 mg/Kg

PAF 300 mg/Kg

CAF 30 mg/Kg

CAF 100 mg/Kg

CAF 300 mg/Kg

Diazepam 3 mg/Kg

Fig: 4.4. Effect of PAF and CAF on maximal electroshock-induced

convulsions in mice.

05

10152025

Dur

atio

n of

con

vulsi

ons (

min

)

Treatment

DMSO

PAF 30 mg/Kg

PAF 100 mg/Kg

PAF 300 mg/Kg

CAF 30 mg/Kg

CAF 100 mg/Kg

Fig: 4.5. Effect of PAF and CAF on duration of pentylenetetrazole-

induced convulsions in mice. Values were mean±S.D (n=6).

68

01020304050607080

Perc

enta

ge in

hibi

tion

of

conv

ulsio

ns

Treatment

PAF 30 mg/Kg

PAF 100 mg/Kg

PAF 300 mg/Kg

CAF 30 mg/Kg

CAF 100 mg/Kg

CAF 300 mg/Kg

Fig: 4.6. Effect of PAF and CAF on pentylenetetrazole-induced

convulsions in mice.

010203040506070

Late

ncy

of c

onvu

lsion

s (m

in)

Treatment

DMSO

PAF 30 mg/Kg

PAF 100 mg/Kg

PAF 300 mg/Kg

CAF 30 mg/Kg

CAF 100 mg/Kg

CAF 300 mg/Kg

Diazepam 4 mg/Kg

Fig: 4.7. Effect of PAF and CAF on isoniazid-induced convulsions in

mice. Values were mean±S.D (n=6).

69

4.9.3.2.3. Antiepileptic activity of Ethanol extract of Acalypha

fruticosa (EAF)





The onset time of THLE for control group animals was found to be

1.03±0.01 sec. EAF treated mice showed the onset time as 1.47±0.02,

2.59±0.02 and 3.76±0.04 sec (p<0.01) respectively at the doses of 30,

100 and 300 mg/kg, p.o. Animals treated with diazepam (3 mg/kg,

p.o.) showed onset time as 2.85±0.02 sec (p<0.01).



sec. Albino mice pretreated with EAF at the doses of 30, 100 and 300

mg/kg, p.o. showed the duration of 55.33±1.21, 46.58±0.92 and



It has been found that the time of onset of THLE in control group

animals was very less when compared to that of animals which

received extract and standard. Duration of THLE in control group

animals was greater when compared to that of animals which received

extract and standard. Albino mice pretreated with EAF at the doses of

30, 100 and 300 mg/kg were provided significant protection from


70


The percentage inhibition achieved in mice pretreated with EAF at

the doses of 30, 100 and 300 mg/kg were 52.52%, 60.03% and

69.03% (p<0.01) respectively when compared to control group

animals. Animals treated with EAF exhibited significant antiepileptic

activity and more percentage of inhibition of convulsions at the doses

of both 100 and 300 mg/kg when compared to diazepam treated

animals (56.81%).

Table 4.9. Effect of EAF on maximal electroshock-induced convulsions

in mice

Group

(n=6)=

6)

Treatment Onset of

THLE (sec)

Duration of

THLE (sec)

Percentage

inhibition of

convulsions

IEAM Gum acacia 1.03±0.01 116.53±2.92 -

IIEAM EAF (30 mg/kg) 1.47±0.02** 55.33±1.21** 52.52**

IIIEAM EAF (100 mg/kg) 2.59±0.02** 46.58±0.92** 60.03**

IVEAM EAF (300 mg/kg) 3.76±0.04** 36.09±1. 84** 69.03**

VEAM Diazepam (3 mg/kg) 2.85±0.02** 50.33±1.86** 56.81**

EAF: Ethanol extract of Acalypha fruticosa; Values were mean±SD


Dunnett’s t test (n=6); **p < 0.01 when compared to Group IEAM

(control).

71

0

20

40

60

80

100

120

140

Dur

atio

n of

TH

LE

(sec

)

Treatment

Gum acacia

EAF 30 mg/Kg

EAF 100 mg/Kg

EAF 300 mg/Kg

Diazepam 3 mg/Kg

Fig: 4.8. Effect of EAF on duration of maximal electroshock-induced

convulsions in mice. Values were mean±S.D (n=6).

01020304050607080

Perc

enta

ge in

hibi

tion

of

conv

ulsi

ons

Treatment

EAF 30 mg/Kg

EAF 100 mg/Kg

EAF 300 mg/Kg

Diazepam 3 mg/Kg

Fig: 4.9. Effect of EAF on maximal electroshock-induced convulsions

in mice.

72






3.43±0.04 min. EAF treated mice exhibited the onset time as



(Phenobarbitone sodium, 40 mg/kg, i.p.) showed 6.46 ±0.02 min

(p<0.01).



22.54±0.02 min. Animals pretreated with EAF at the doses of 30, 100

and 300 mg/kg, p.o. exhibited the duration as 9.55±0.02, 7.52±0.05

and 6.58±0.01 min (p<0.01) respectively. The standard group mice


(p<0.01).


less when compared to the animals treated with extract and standard.


compared to the extract and standard treated animals. It has been

found that animals pretreated with EAF were significantly protected

from convulsions induced by PTZ in a dose-dependent manner.

73


The percentage of inhibition achieved in EAF treated mice were



Animals which were treated with EAF exhibited significant and dose-

dependent antiepileptic activity and more percentage inhibition of

convulsions when compared to Phenobarbitone sodium treated mice

(50.82%, p<0.01).

Table 4.10. Effect of EAF on Pentylenetetrazole (PTZ)-induced

convulsions in mice

Group

(n=6)=

6)

Treatment

Onset of

convulsions

(min)

Duration of

convulsions

(min)

Percentage

inhibition of

convulsions

IEAP Gum acacia 3.43±0.04 22.54±0.02 --

IIEAP EAF (30 mg/kg) 4.38±0.05** 9.55±0.02** 57.62**

IIIEAP EAF (100 mg/kg) 4.54±0.02** 7.52±0.05** 66.63**

IVEAP EAF (300 mg/kg) 5.14±0.03** 6.58±0.01** 70.82**

VEAP Phenobarbitone sodium

(40 mg/kg, i.p.) 6.46±0.02** 11.09±0.03** 50.82**



Dunnett’s t test (n=6); **p < 0.01 when compared to Group IEAP

(control).

74

0

5

10

15

20

25

Dur

atio

n of

con

vulsi

ons

(min

)

Treatment

Gum acacia

EAF 30 mg/Kg

EAF 100 mg/Kg

EAF 300 mg/Kg

Phenobarbitone sodium 40 mg/Kg

Fig: 4.10. Effect of EAF on duration of pentylenetetrazole-induced


01020304050607080

Perc

enta

ge in

hibi

tion

of

conv

ulsio

ns

Treatment

EAF 30 mg/Kg

EAF 100 mg/Kg

EAF 300 mg/Kg


Fig: 4.11. Effect of EAF on pentylenetetrazole-induced convulsions in

mice.

75





25.15±0.28 min. Albino mice pretreated with EAF showed the latency


(p<0.01) respectively at the doses of 30, 100 and 300 mg/kg, p.o. The

standard group mice (diazepam 4 mg/kg, i.p.) showed 63.27±0.04 min

(p<0.01).


when compared to that of animals pretreated with extract and

standard. EAF treated animals showed the latency time more than

that of control group animals and less than that of standard group

animals. Although all the three doses of EAF significantly delayed the

latency of convulsions in a dose-dependent manner but failed to

protect mice against mortality.

Table 4.11. Effect of EAF on Isoniazid (INH)-induced convulsions in

mice


convulsions (min)

IEAI Gum acacia 25.15±0.28

IIEAI EAF (30 mg/kg) 30.08±0.05**

IIIEAI EAF (100 mg/kg) 32.52±0.06**

IVEAI EAF (300 mg/kg) 36.06±0.04**

VEAI Diazepam (4 mg/kg, i.p.) 63.27±0.04**



Dunnett’s t test (n=6); **p < 0.01 when compared to Group IEAI

(control).

76

010203040506070

Lat

ency

of c

onvu

sions

(min

)

Treatment

Gum acacia

EAF 30 mg/Kg

EAF 100 mg/Kg

EAF 300 mg/Kg

Diazepam 4 mg/Kg

Fig: 4.12. Effect of EAF on isoniazid-induced convulsions in mice.

Values were mean±S.D (n=6).

4.9.3.2.4. Anti-epileptic activity of Aqueous extract of Acalypha

fruticosa (AAF)





The onset time of THLE in control group animals was 1.52±0.05

sec. Animals which received AAF at the doses of 30, 100 and 300

mg/kg, p.o. showed the onset time as 2.29±0.14, 2.51±0.32 and




The duration of THLE in control group animals was 93.56 ±0.33

sec. Albino mice pretreated with AAF showed the duration of

77

60.28±0.40, 51.59±0.35 and 42.22±0.22 sec (p<0.01) respectively at

the doses of 30, 100 and 300 mg/kg, p.o. The standard group mice


The time of onset of THLE in control group animals was very less

when compared to the extract and standard treated animals. Duration

of THLE in control group animals was greater when compared to the

extract and standard treated animals. AAF significantly protected the

mice from convulsions induced by electroshock method in a dose-

dependent manner.


The percentage inhibition achieved in AAF treated mice were

35.57% (30 mg/kg), 44.85% (100 mg/kg) and 54.87% (300 mg/kg)

(p<0.01) respectively when compared to control group animals.

Animals pretreated with AAF exhibited significant antiepileptic activity

and less percentage of inhibition of convulsions when compared to

diazepam treated animals (57.69%, p<0.01).

78

Table 4.12. Effect of AAF on maximal electroshock-induced

convulsions in mice

Group

(n=6) Treatment

Onset of

THLE (sec)

Duration of

THLE (sec)

Percentage

inhibition of

convulsions

IAAM Distilled water 1.52±0.05 93.56 ±0.33 -

IIAAM AAF (30 mg/kg) 2.29±0.14** 60.28±0.40** 35.57**

IIIAAM AAF (100 mg/kg) 2.51±0.32** 51.59±0.35** 44.85**

IVAAM AAF (300 mg/kg) 2.88±0.04** 42.22±0.22** 54.87**

VAAM Diazepam (3 mg/kg) 3.53±0.25** 39.59±0.35** 57.69**

AAF: Aqueous extract of Acalypha fruticosa; Values were mean±SD


Dunnett’s t test (n=6); **p < 0.01 when compared to Group IAAM

(control).

0102030405060708090

100

Dur

atio

n of

TH

LE (s

ec)

Treatment

Distilled water

AAF 30 mg/Kg

AAF 100 mg/Kg

AAF 300 mg/Kg

Diazepam 3 mg/Kg

Fig: 4.13. Effect of AAF on duration of maximal electroshock-induced


79

0

10

20

30

40

50

60

70

Perc

enta

ge in

hibi

tion

of

conv

ulsi

ons

Treatment

AAF 30 mg/Kg

AAF 100 mg/Kg

AAF 300 mg/Kg

Diazepam 3 mg/Kg

Fig: 4.14. Effect of AAF on maximal electroshock-induced convulsions

in mice.






3.06±0.02 min. AAF treated mice exhibited the onset time as



(Phenobarbitone sodium, 40 mg/kg, i.p.) showed 6.46 ±0.02 min

(p<0.01).



22.54±0.02 min. AAF treated mice exhibited the duration as


80

doses of 30, 100 and 300 mg/kg, p.o. Albino mice pretreated with

Phenobarbitone sodium, 40 mg/kg, i.p. showed 11.09±0.03 min

(p<0.01).


less when compared to the extract and standard group animals.


compared to the extract and standard group animals. Albino mice

pretreated with AAF at the doses of 30, 100 and 300 mg/kg were

provided significant protection from convulsions induced by PTZ.


The percentage inhibition achieved in mice which received AAF

were 50.19% (30 mg/kg), 58.16% (100 mg/kg) and 64.44% (300

mg/kg) (p<0.01) respectively when compared to control group

animals. AAF treated mice exhibited significant antiepileptic activity

and more percentage of inhibition of convulsions at both 100 and 300

mg/kg when compared to Phenobarbitone sodium 40 mg/kg, i.p.

(50.82%, p<0.01).

81

Table 4.13. Effect of AAF on Pentylenetetrazole (PTZ)-induced

convulsions in mice

Group

(n=6)=

6)

Treatment

Onset of

convulsions

(min)

Duration of

convulsions

(min)

Percentage

inhibition of

convulsions

IAAP Distilled water 3.06±0.020. 22.54±0.02 -

IIAAP AAF (30 mg/kg) 3.11±0.04** 11.23±0.03** 50.19**

IIIAAP AAF (100 mg/kg) 3.53±0.04** 9.43±0.03** 58.16**

IVAAP AAF (300 mg/kg) 4.05±0.03** 8.02±0.21** 64.44**

VAAP Phenobarbitone sodium

(40 mg/kg, i.p.) 6.46 ±0.02** 11.09±0.03** 50.82**



Dunnett’s t test (n=6); **p < 0.01 when compared to Group IAAP

(control).

0

5

10

15

20

25

Dur

atio

n of

con

vulsi

ons

(min

)

Treatment

Distilled water

AAF 30 mg/Kg

AAF 100 mg/Kg

AAF 300 mg/Kg

Phenobarbitonesodium 40 mg/Kg

Fig: 4.15. Effect of AAF on duration of pentylenetetrazole-induced


82

010203040506070

Perc

enta

ge in

hibi

tion

of

conv

ulsio

ns

Treatment

AAF 30 mg/Kg

AAF 100 mg/Kg

AAF 300 mg/Kg


Fig: 4.16. Effect of AAF on pentylenetetrazole-induced convulsions in

mice.


The average latency of onset of convulsions were presented in

Table 4.14.


In control group animals, the latency of convulsions was

25.15±0.28 min. Albino mice pretreated with AAF showed the latency


(p<0.01) respectively at the doses of 30, 100 and 300 mg/kg, p.o.

Animals belonging to standard group (diazepam 4 mg/kg, i.p.) showed

63.27±0.04 min (p<0.01).


when compared to the extract and standard. All the three doses of

AAF showed the latency time more than that of control group animals

and less than that of standard group animals i.e., diazepam. Although

83

AAF exhibited dose-dependent delay in the latency of convulsions but

failed to protect the animals from mortality.

Table 4.14. Effect of AAF on Isoniazid (INH)-induced convulsions in

mice


convulsions (min) IAAI Distilled water 25.15±0.28

IIAAI AAF (30 mg/kg) 28.58±0.22**

IIIAAI AAF (100 mg/kg) 30.33±0.03**

IVAAI AAF (300 mg/kg) 33.59±0.22**

VAAI Diazepam (4 mg/kg, i.p.) 63.27±0.04**



Dunnett’s t test (n=6); **p < 0.01 when compared to Group IAAI

(control).

0

10

20

30

40

50

60

70

Lat

ency

of c

onvu

lsion

s (m

in)

Treatment

Distilled water

AAF 30 mg/Kg

AAF 100 mg/Kg

AAF 300 mg/Kg

Diazepam 4 mg/Kg

Fig: 4.17. Effect of AAF on isoniazid-induced convulsions in mice.

Values were mean±S.D (n=6).

84

4.10. Discussion

Epilepsy is one of the major neurological disorders characterized

by sporadic episodes of abnormal behavior, convulsive seizures,

sensory disturbance and loss of consciousness or all of these

symptoms resulting from a brain dysfunction or an abnormal

discharge of cerebral neurons [35].

Higher prevalence, cultural and social stigma, lack of awareness

and non-availability of proper diagnostic and treatment facilities are

some of the major reasons for the increasing number of people with

epilepsy in the developing countries. All the currently available AEDs

are associated with side-effects, long-term toxicity, teratogenic effects

and about 40% patients are refractory to therapeutic intervention and

thus its effective and safe therapy still remains a challenge [44-46].

Hence there is a mere need to search for AEDs from alternative

sources i.e., exploitation of medicinal plants.

Medicinal plants in traditional medicine can become an invaluable

source for search of new antiepileptic compounds. Literature survey

revealed that many plants like Aegle marmelos, Asparagus racemosus,

Carissa edulis, Cyperus articulatus, Delphinium denudatum, Hibiscus

rosa and Jasminum grandflorum acclaim to possess antiepileptic

activity [57, 58, 96, 122-123].

Acalypha fruticosa is a shrub belonging to the family of

Euphorbiaceae. Aerial parts of Acalypha fruticosa were traditionally

used to treat epilepsy [21]. But till today there were no reports to

85

justify its claim. Hence the present work was designed to evaluate the

antiepileptic activity of Acalypha fruticosa.

In the present study, four different extracts were prepared by using

solvents of increasing polarity like petroleum ether, chloroform,

ethanol and water. Non-polar solvents have low dielectric constants

and dissolve non-polar solutes with similar internal pressures through

induced dipole interactions. Petroleum ether is a non-polar solvent

which solubilises non-polar compounds like steroids and

triterpenoids. Chloroform extracts non-polar to intermediately polar

compounds such as steroids, triterpenoids, flavonoids. Ethanol

dissolves most of the secondary metabolites such as steroids,

triterpenoids, flavonoids, tannins, saponins and enhance their release

from cellular matrix/cell surface. The polar components like

polysaccharides, phenols, aldehydes, ketones, amines, saponins and

other oxygen containing compounds dissolve in water due to

formation of hydrogen bonding [124]. Thus petroleum ether,

chloroform, ethanol and aqueous extracts of Acalypha fruticosa were

prepared to predict which phytoconstituents are responsible for the

remarkable antiepileptic activity.

In preliminary phytochemical studies, the chief phytoconstituents

present in the different extracts of Acalypha fruticosa were alkaloids,

steroids, carbohydrates, tannins, flavanoids, saponins, lipids and

proteins.

86

In acute toxicity studies, petroleum ether, chloroform, ethanol and

aqueous extracts of Acalypha fruticosa were found to be safe upto

1000 mg/kg, (p.o.) body weight. Hence three doses i.e., 30, 100 and

300 mg/kg, p.o. were selected for all the extracts to evaluate

antiepileptic activity.

To screen the antiepileptic activity, most extensively studied, well

established and simple animal seizure models viz. maximal

electroshock, pentylenetetrazole and isoniazid-induced seizures in

mice were selected. Another advantage of using the above models is

the pharmacological profiles were comparable to the human condition

[33-34].

The MES test identifies compounds/extracts which prevent seizure

spread [29-30]. In this model, all the extracts of Acalypha fruticosa

significantly and dose dependently increased the onset time of THLE

and decreased the duration of THLE. But ethanol extract exhibited

maximum significant antiepileptic activity at 300 mg/kg (69.03%). The

order of antiepileptic activity for various extracts in MES model was

ethanol>chloroform>petroleum ether>aqueous (chloroform extract-

66.33%, petroleum ether extract-62.33% and aqueous extract-

54.87%). All the extracts of Acalypha fruticosa might prevent the

seizure spread and contribute to the activity. But the maximum

antiepileptic activity of the ethanol extract may be due to the presence

of phytoconstituents such as tannins and flavonoids.

PTZ test identifies compounds/extracts which primarily raise

seizure threshold [29-30]. In this model, all the extracts of Acalypha

87

fruticosa significantly increased the onset time of convulsions and

decreased the duration of convulsions in a dose-dependent manner.

But ethanol extract showed maximum antiepileptic activity at 300

mg/kg (70.82%) followed by chloroform extract (68.20%), petroleum

ether extract (66.49%) and aqueous extract (64.44%). In this model,

seizure threshold may be raised by all the extracts of Acalypha

fruticosa but the potent activity of ethanol extract may be because of

phytoconstituents like tannins and flavonoids present in the extract.

Isoniazid is an antitubercular drug which was shown to lower the

content of brain GABA in humans to approximately the same extent in

rats and mice [32]. In this model, all the four extracts of aerial parts of

Acalypha fruticosa delayed the latency of convulsions but could not

protect the mice from mortality. At 300 mg/kg dose, ethanol extract

possessed maximum delay in latency of convulsions. In this model,

the extracts act as GABA agonists but unable to increase GABA levels

in brain.

All the extracts exhibited significant antiepileptic activity in all

three tested models. The order of activity is AAF<PAF<CAF<EAF. The

observed antiepileptic activity of AAF in all models could be due to the

presence of tannins. Presence of steroids may attribute to the potent

antiepileptic activity of PAF than AAF because steroids are involved in

neuromodulatory effects [125]. Antiepileptic activity of CAF may be

due to the presence of steroids and flavonoids because flavonoids and

sterols have been involved in central inhibitory and neuromodulatory

effects [126]. Maximum activity of EAF may be because of combined

88

effects of steroids, tannins and flavonoids. Studies carried out till date

suggests that flavonoids inhibit voltage gated sodium channels,

activate Ca+ activated K+ channels, stimulate GABAergic inhibition,

interact with opioid receptors, inhibit NMDA receptors and exhibit

antioxidant actions via modulation of nitric oxide and xanthine

oxidase pathways and by leukocytic immobilization, one or more of

these mechanisms are involved in suppression of epileptic seizures

[127].

Overall the present study demonstrated that the ethanol extract of

aerial parts of Acalypha fruticosa exhibited maximum antiepileptic

activity in all tested models. The order of activity of the extracts were

ethanol> chloroform>petroleum ether>aqueous. Ethanol extract may

act at seizure focus, prevent spread of the seizure and suppresses

THLE induced by MES. In PTZ model, the extract might raised the

seizure threshold or act as GABA agonist and enhanced GABAergic

neurotransmission by increasing GABA levels in brain by facilitating

the opening of GABA-activated chloride channels at GABAA receptors.

The ethanol extract increased the latency of convulsions in INH model

but could not protect the mice from mortality. So, it may act as GABA

agonist but unable to stimulate GABA synthesis. Further, our results

indicated that the beneficial effect of ethanol extract of Acalypha

fruticosa in epilepsy is due to the presence of steroids, tannins and

flavonoids. Present study justify the traditional use of Acalypha

fruticosa in folk medicine.

Documents

CHAPTER-4 PLANT PROFILE AND EVALUATION OF …shodhganga.inflibnet.ac.in/bitstream/10603/70545/11/11_chapter 4.pdf · PLANT PROFILE AND EVALUATION OF ANTIEPILEPTIC ACTIVITY OF ACALYPHA