evaluation of cardiotonic effect of hydroalcoholic … · e-issn: 2278-5191 | oct-dec 2013 | volume...

International Journal of Pharmaceutical

Biological and Chemical Sciences

e-ISSN: 2278-5191

International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS)

e-ISSN: 2278-5191 | OCT-DEC 2013 | VOLUME 2 | ISSUE 4 | 20-25 www.ijpbcs.net or www.ijpbcs.com

Research Article

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EVALUATION OF CARDIOTONIC EFFECT OF HYDROALCOHOLIC LEAF

EXTRACT OF NERIUM INDICUM: AN ANIMAL STUDY

Sangita Totade* & S.John Premendran

Department of Pharmacology, Jawaharlal Nehru Medical College, DMIMS (Deemed University),

Sawangi (Meghe), Wardha-442004. Maharashtra

*Corresponding Author Email: sangitabele05@gmail.com

INTRODUCTION India is perhaps the largest producer of Medicinal herbs

and is rightly called the Botanical garden of the world

(1).Some 130 drugs are currently used which are

chemical entities either as direct extract from plant or modifying through further synthesis (2).According to

WHO over 80% of the world people rely on traditional

herbs based system of medicine to provide them with

primary healthcare (3). CCF is a progressive complex

clinical syndrome characterised by dyspnoea, fatigue,

fluid retention and hypertension. The main cause of

C.C.F. is coronary artery disease. Current

pharmacological therapy for CCF is Digitalis, ACE

Inhibitors, ACE antagonist, Diuretics. Digoxin is the

main drug to treat the CCF. Having low margin of safty

and may produce toxicity. So to discover the potential drug with less toxicity & wide margin of safty Narium

indicum belongs to family Apocynaceae. It is cultivated

throught india. It contains sterol glycoside like digitalis

and claimed for its cardiotonic activity. Neriun indicum

has also claimed to have medicinal properties like

Diuretic, anthelmintics (4) Neriun indicum has been

investigated for cardiotonic activity(5,6), antifungal,

Antispasmotic & anticancer(7 8 ) keeping in view the

limitation of available cardiotonic claim on the plant, the

present study has been undertaken to evaluate the

cardiotonic activity of Nerium Indicum.

MATERIALS & METHODS Plant material-The Nerium indicum leaves was collected

and dried under shade. Dried leaves were grind to obtain

powder. The hydroalcoholic extract of the powder was

prepared by the process of continuous extraction (soxhlation) such that 1 g of hydroalcoholic extract is

equivalent to 2 g of crude drug. Animal- adult healthy

frog, healthy albino rates and rabbit were taken. All

study were performed in accordance with institutional

Animal ethical committee. (IAECNO

52/PO/01/a/CPCSEA)

EXPERIMENTAL PROTOCOL

1. Effect of the extract of on hypodynamic frog heart-the frog were sacrificed by pithing. hypodynamic

heart developed with half calcium ringer .The

hydroalcoholic extract was made into a solution by

adjusted with saline to obtain various

concentration of extract. The extract was

administered in gradient concentration. The

responses were recorded on Sherrington

kymograph at a speed of 0-12 mm/sec. 2) (9).

2. Effect of extract on isolated rat heart-the rat was

sacrificed and heart was isolated briskly and

washed with saline and mounted on lung heart apparatus and graded dose were given and

response were recorded on student

physiograph.(10)

ABSTRACT:

Introduction: Our traditional heritage of medicine which is based on the use of herbs and Plant medicine. Digoxin for

congestive cardiac failure and Quinine for falciparum malaria are the life saving drug molecule available to treat were

discovered from natural plant resource. Objectives: To evaluate cardiotonic activity of hydroalcoholic leaf extract of

Nerium Indicum. Material & Methods: Perfused Frog heart & isolated rat, rabbit heart were used. The hydroalcoholic

extract of leaves of Nerium Indicum was prepared by the process of continuous extraction (soxhlation) and given

in graded dose. Result : The extraction showed dose dependent positive ionotropic effect on perfused hypodynamic frog

heart & isolated rabbit heart while on rat heart no effect was found Conclusion:The result obtained in this study indicated

that the leaf extract of nerium Indicum possess significant cardiotonic activity on experimental induces hypodynamic frog

& rabbit heart

KEYWORDS: Nerium Indicum, Cardiotonic Activity, congestive Cardiac failuar, Hypodynamic heart.

* Sangita Totade et al; EVALUATION OF CARDIOTONIC EFFECT OF HYDROALCOHOLIC LEAF EXTRACT OF NERIUM INDICUM……

International Journal of Pharmaceutical, Biological and Chemical Sciences | e-ISSN: 2278-5191 | OCT-DEC 2013 | VOLUME 2 | ISSUE 4 | 20-25| www.ijpbcs.net

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3. Effect of extract on isolated rabbit heart-Rabbit was

sacrificed and heart was isolated briskly and

washed with saline and mounted on lung heart

apparatus and graded dose were given and

response were recorded on student’s physiograph.

Result were analysed by student p test. P <05 or less was

accepted as significant

RESULT In hypodynamic frog and rabbit heart the hydroalcoholic

extract nerium indicum produced dose dependent

positive inotropic effect and increase in cardiac output.

The extract of Nerium indicum did not produced any

effect on isolated rat heart.The force of contraction and

the heart rate did not changed as the dose increased.

1. Nerium Indicum produced increase in the force of contraction of the hypo dynamic frog heart.

Maximum increase in the force of contraction was

evident with the dose of 400µg/ml. Further increase

in dose also brought about sustained increase force

of contraction. Above of 960µg/ml produced

cardiac arrest (Table No: 1) & (Fig No1a, 1B, 1C)

Table 1: Effect of Extract Nerium Indicum on Hypo dynamic Frog Heart

Figure 1: A Effect of Extract Nerium Indicum on Hypo dynamic Frog Heart

Sr.

No

Dose/Conc.

µg/ml

Response Inference

Contraction Heart Rate/Min.

Mean ± SEM

1. Depleted Ringer Deceased 32 ± 1.40 Inhibition

2. 40 Increased 32 ± 1.00 Stimulation

3. 120 Increased 32 ± 1.00 Stimulation

4. 240 Increased 28 ± 1.46 Stimulation

5. 400 Increased 20 ± 1.93* Stimulation

6. 800 Increased 8 ± 0.25 Stimulation

7. 960

Increased 1 ± 0.95***

Cardiac arrest

P value- * < 0.05 ** <0.01 < *** <0.001

* Sangita Totade et al; EVALUATION OF CARDIOTONIC EFFECT OF HYDROALCOHOLIC LEAF EXTRACT OF NERIUM INDICUM……

International Journal of Pharmaceutical, Biological and Chemical Sciences | e-ISSN: 2278-5191 | OCT-DEC 2013 | VOLUME 2 | ISSUE 4 | 20-25| www.ijpbcs.net

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(D.R.-Depleted Ringer, T. D. - Test Drug)

(T. D. - Test Drug)

2. The extract of Nerium indicum did not produced any effect on isolated rat heart. The force of contraction and the heart

rate did not change as the dose increased. (Table 2), (Fig 2).

Table 2: Effect of Nerium Indicum on Rat Heart

Sr.No. Dose Conc.

µg/ml

Response

Contraction Heart Rate/Min.

1. 100 No Effect No Effect

2.

400

No Effect

No Effect

3.

1000

No Effect

No Effect

4.

2000

No Effect

No Effect

P VALUE- *<0.O5 ** <O.O1 ***<O.OO1

* Sangita Totade et al; EVALUATION OF CARDIOTONIC EFFECT OF HYDROALCOHOLIC LEAF EXTRACT OF NERIUM INDICUM……

International Journal of Pharmaceutical, Biological and Chemical Sciences | e-ISSN: 2278-5191 | OCT-DEC 2013 | VOLUME 2 | ISSUE 4 | 20-25| www.ijpbcs.net

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Fig 2: Effect of Nerium Indicum on Rat Heart

(TD-Test drug)

3. The extract of Nerium indicum produced increase in force of contraction (on isolated rabbit heart. The maximum

increase in force of contraction was observed at 800µg/ml. At 8000µg/ml the inhibitory effect was observed, the heart

rate and force of contraction was decreased. The heart rate gradually decreased and finally at 8000µg/ml the heart ceased to function. (Table 3), (Fig 3a & 3B).

Table 3 - Effect of Nerium Indicum on Isolated Rabbit Heart

P VALUE- *<0.O5 ** <O.O1 ***<O.OO1

Sr.No

Dose Conc.

µg/ml

Response Inference

Contraction Heart Rate/Min.

1. 80 Increased 200±0.43 Stimulation

2. 200 Increased 200±0.61 Stimulation

3. 600 Increased 120±0.52* Stimulation

4. 2000 Decreased 100±0.41** Stimulation

5. 4000 Decreased 100±0.36** Stimulation

6. 8000 Decreased 90±0.27** Inhibition

* Sangita Totade et al; EVALUATION OF CARDIOTONIC EFFECT OF HYDROALCOHOLIC LEAF EXTRACT OF NERIUM INDICUM……

International Journal of Pharmaceutical, Biological and Chemical Sciences | e-ISSN: 2278-5191 | OCT-DEC 2013 | VOLUME 2 | ISSUE 4 | 20-25| www.ijpbcs.net

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3. Effect of Nerium Indicum on Isolated Rabbit Heart

(TD-Test drug)

DISCUSSION Though the high diuretics and ACE inhibitors are being

used in the treatment of c.c.f., digitalis is still the most

effective drug capable of restoring cardiac compensation

specialy in patient with dialated heart and low regection

fraction. All digitalis preparation available today for the

treatment of congestive cardiac failure are known to

cause sign and symptoms of intoxication and safety (11).

Hence introduction of any drug more potent and less

toxic than digitalis would be advancement in the therapy

of congestive heart failure. In the present study the hydroalcoholic extract of Nerium indicum produced a

dose dependent positive ionotropic effect on

hypodynamic frog and rabbit heart. The alcoholic extract

obtain from the leaves of nerium indicum has been

reported to posses potent cariotonic activity. It was also

found useful when tried on patient of congestive heart

failure.It is reported that alcoholic extract of Nerium

indicum leaves produced a positive inotropic effect and

bradicardia in isolated frog and rabbite heart(12). Overall

the present study clearly indicated that leaves of nerium

indicum plant posses positive ionotropic effect.

CONCLUTION

In the current study reveals that the hydroalcoholic

leaves of nerium indicum posses good cariotonic activity in hypodynamic frog and rabbit heart .in the rat heart

nedium indicum did not changed force of contraction

like the digitalis,hence it is inferred that nerium indicum

posses cariotonic activity and could be usefull in

treatment of congestive cardiac failure after extensive

animal and clinical trials

REFERENCES 1. Chouthari R.D. Herbal drug industry. A Practical

Approach to Industrial Pharmacology; 1st Ed. Introduction; 4-6, 1996.

2. Batt. Ayurveda Drug Industry, First National Symposium; 10-20 1999.

3. Barrier Man R.M. Traditional medicine in Morden health care .World Health Forum; 3 (1): 8-13, 1992.

4. Warrier P.K. Indian Medicinal Plant.Vol.4:126-127,1996

5. Chopra R.N., Chopra I.C. A review of work on Indian Medicinal Plants. Indian Council of Medical Research. New Delhi; 81, 1955.

6. Kohli R.P.,Singh.,et al .A Study of Cardiotonic activity of Nerium indicum on heart-lung preparation of dog. J.Res.Indian Med.; 4(1):54, 1999.

7. Trivedi V.P.,et al. A clinical study of the effect of Tincture of Nerium Indicum Linn.. On the Respiratory

* Sangita Totade et al; EVALUATION OF CARDIOTONIC EFFECT OF HYDROALCOHOLIC LEAF EXTRACT OF NERIUM INDICUM……

International Journal of Pharmaceutical, Biological and Chemical Sciences | e-ISSN: 2278-5191 | OCT-DEC 2013 | VOLUME 2 | ISSUE 4 | 20-25| www.ijpbcs.net

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tract involvement in case of congestive cardiac faiure; 162-167, 1997.

8. Dhar M.L.,Dhar M.M.,et.al. Screening of Indian plants for biological activity,Part I.Indian J. Exp.Bio.;6,232,1968.

9. J.H. Burn. Practical pharmacology (Blackwell scientific

publications: Oxford, 1952).

10. MurierA.R. The effect of divalent cations on the ultra structure of the perfused rat heart.Anat,;, 101(2):239-261,1967.

11. Goodman& gillman’s.The Pharmacological basis of Therapeutics; Ed10 th;, 901-933, 2001.

12. Sanyal P.K. &., Das H.K. Pharmacological study of the tincture of (Rakta - Karabi Nerium Indicum Odorum Soland) Flowres. Proc.43 Indian Sci, Cong;,

Pt.III:350,1956.

*Corresponding author address:

Sangita Totade* Department of Pharmacology,

Jawaharlal Nehru Medical College, DMIMS (Deemed

University), Sawangi (Meghe), Wardha-442004. Maharashtra