Local Anaesthetic Activity of Calotropis gigantea Latex in Frog and Guinea Pig

 

 

KK Rajasekhar*, V Shankarananth, M Rajagowtham,  B Gowtham Kumar, B Thejnayan and M Pavankumar

Dept of Pharmaceutical chemistry,  Sri Padmavathi School of Pharmacy,Tiruchanoor, Tirupati-517503, A.P.,India.

 

ABSTRACT:

This work evaluated the local anaesthetic activity of milky latex obtained from Calotropis gigantea using three different experimental models in frog and Guinea pig. The latex at dilution 1:10 showed the anaesthetic activity compared to the standard drug xylocaine (0.2%). The methods used are nerve block or lumbar plexus anaesthesia and muscle twitch in frog, infiltration anaesthesia in Guinea pig. It was concluded that latex of Calotropis gigantea (1:10 dilution ) exhibited significant local anaesthetic activity.

 

KEY WORDS: Calotropis gigantea,milky latex,local anaesthetic activity,nerve block method,muscle twitch method and infiltration method .

 

INTRODUCTION:

Calotropis gigantea (Crown flower) is a species of Calotropis, native to India, Indonesia, Malaysia, Philippines, Thailand, Sri Lanka, and China. It is a large shrub growing to 4 m tall. It has clusters of waxy flowers that are either white in colour. Each flower consists of five pointed petals and a small, elegant "crown" rising from the centre, which holds the stamens. The plant has oval, light green leaves and milky stem. Calotropis is used as a traditional medicinal plant1 with unique properties2.Traditionally Calotropis is used alone or with other medicinals3 to treat common disease such as fevers, rheumatism, indigestion, cough, cold, eczema, asthma, elephantiasis, nausea, vomiting, diarrohea4. According to Ayurveda, dried whole plant is a good tonic, expectorant, depurative, and anthelmintic. The dried root bark is a substitute for ipecacuanha. The root bark is febrifuge, anthelmintic, depurative, expectorant, and laxative. The powdered root used in asthma, bronchitis, and dyspepsia. The leaves are useful in the treatment of paralysis, arthralgia, swellings, and intermittent fevers. The flowers are bitter, digestive, astringent, stomachic, anthelmintic, and tonic5. Calotropis is also a reputed homoeopathic drug6.

 

Calotropis yields a durable fiber (commercially known as Bowstring of India) useful for ropes, carpets, fishing nets, and sewing thread. Floss, obtained from seeds, is used for stuffing purposes. Fermented mixture of Calotropis and salt is used to remove the hair from goat skins for production of "nari leather" and of sheep skins to make leather which is much used for inexpensive book-binding7.

 

Allelopathic effects of Calotropis on different agricultural crops have not been well studied. Extracts of different plant parts viz. root, stem, leaf ,and stem+leaf of Calatropis affect germination and seedling vigor of many agricultural crops have been reported8. However, extracts of Calatropis failed to produce any detrimental effects on weeds such as Chenopodium album Melilotus alba, Melilotus indica, Sphaeranthus indicus, and Phalaris minor9.

Literature survey revealed that the latex of calotropis procera10 and Tabernaemontana coronaria11 exhibited local anaesthetic activity in frog (nerve block anaesthesia and muscle twitch method)  and Guinea pig(infiltration method), and no researcher has yet reported local anaesthetic activity of Calotropis gigantea. Therefore, it is worth conducting an investigation on the local anaesthetic  activity of C. gigantea latex.


Local anaesthetics are the agents which prevent or relieve pain by interrupting nerve conduction. They bind to a specific receptor site within the pore of the sodium channels in nerves and block ion movement through this pore. Their action is restricted to the site of application and rapidly reverses upon diffusion from the site of action in the nerve12. They are administered in variety of routes such as topical anaesthesia, infiltration anaesthesia, field block anaesthesia, nerve block anaesthesia, intravenous regional anaesthesia, spinal anaesthesia and epidural anaesthesia, and have potential to produce deleterious side effects 13-17. The present study was undertaken to screen the local anaesthetic activity of latex obtained from   Calotropis gigantea.

 

MATERIALS AND METHODS:

Chemicals and equipments: Milky latex of Calotropis gigantea, centrifuge, Distilled water,0.1N Hcl, Normal saline(0.65% Nacl),Xylocaine(0.25w/v),Fixing solution, Hair depleting agent, Frog board, Frog stand, Hammer, Sharp pins, Plastic tray, Sherrington recording drum, Drum-cylinder with smoked paper wrapped, Myographic lever, Surgical instruments and Dissection box.

 

Animals: Frog (bigger size) and Guinea pig.

Methods: Nerve block anaesthesia method and Muscle twitch method (Frog), Infiltration anaesthesia method (Guinea pig).

 

Collection of milky latex:

The milky latex was collected usually between 8 am and 10 am by cutting the tips of young branches of C. gigantea. Then 1 ml of latex was centrifuged at 5,000 r.p.m after being diluted 10 times its volume with distilled water. The gummy pellet was discarded and the supernatant liquid was used for evaluation of local anaesthetic activity.

 

Evaluation of local anaesthetic activity:

Nerve block anaesthesia18:

Two frogs (150 gm)were decerebrated and the upper part of the spinal cord was destroyed with the help of pithing  needle. Abdomen was cut opened and all the abdominal organs were removed, to get a pouch(sac) made of abdominal walls. The sciatic nerve was exposed to standard (Xylocaine) and  test drug(1:10 dilution of milky latex) separately.

 

Application of drugs:

Piece of cotton was immersed in 0.2% xylocaine solution and placed in the abdominal pouch of 1st frog. Similarly, separate piece of cotton was immersed in 1:10 dilution of milky latex and then placed in abdominal pouch of 2nd frog.

 

Leg withdrawal action:

The frog board was placed vertically so that the hind legs of frog hang freely. Right and Left hind legs were immersed in the beakers containing 0.1 N Hcl and normal saline. Sudden leg withdrawal action was noted before and after administration of standard and test.

 

Muscle twitch method:

The frog is sacrificed by euthanasia and gastrenimus sciatic muscle nerve preparation is dissected out from the animal. It was placed in the Lucas moist chamber filled with frog’s saline. The knee joint was fixed to one cork of the chamber while the muscle tendon was tied to the hook of the lever. The speed of the drum was adjusted to the maximum and the lever is adjusted in horizontal line and the after load screw adjusted such that it touches the hook lever. The nerve was placed on the electrodes and to avoid getting it dried, cotton soaked in saline was placed over it. The lever was allowed to touch lightly on drum. Its position was adjusted about one inch above the base. The base line was drawn till a simple muscle curve was obtained. Position of contact was changed to study the influence (local anaesthetic activity) of standard (Xylocaine) and test drug 19 (1:10 dilution of milky latex).

 

Table No.1: Nerve block anaesthesia method: Comparison between standard and test drug for local anaesthetic activity

Standard vs Test (Milky latex)

Responses

Left (leg)

Right (leg)

Before administration of the standard drug

+

+

Standard drug (xylocaine)

 

 

0 minute

--

--

1 minute

+

+

2 minutes

+

+

3 minutes

+

+

4 minutes

-

-

5 minutes

-

-

6 minutes

-

-

7 minutes

-

-

8 minutes

-

-

9 minutes

-

-

10 minutes

-

-

11 minutes

-                    

-                    

Before administration of the test drug

+

+

Test drug 1:10 concentration

 

 

0 minute

 

 

1 minute

+

+

2 minutes

+

+

3 minutes

+

+

4 minutes

+

+

5 minutes

-

-

6 minutes

-

-

7 minutes

-

-

8 minutes

-

-

9 minutes

-                    

-

10 minutes

+

+

 

 

Infiltration Anaesthesia:

Two healthy adult male Guinea pigs were taken and fur on their back was removed by using depleting agents. The depleted area was washed with normal saline and allowed to dry. Then the standard (Xylocaine) and test drug (1:10 dilution) was injected intradermally. Squeak or twitch response of animal upon touching the injection site with sharp pin was marked as (+) and (-) if the animal does not show any response to pin prick20.

 

RESULTS AND DISCUSSION:

Action of the drug:

0.1N Hcl in beaker was used to find out the anaesthetic activity of the milky latex extract from Calotropis gigantea.

In Nerve block anaesthesia method, before administration of the drug, when the acid has been contacted with the hind leg there was a sudden withdrawal of leg from the beaker in which the 0.1N Hcl was taken. After administration of the drug, when tested with Hcl, there was absence of withdrawal of leg from the acid. Hence it was proved that the milky latex from Calotropis gigantea had local anaesthetic activity. The test drug (1:10) Concentration exhibited marked activity like that of the standard drug (xylocaine).

 

Table No.2: Muscle Twitch method: Comparison between standard and test drug for local anaesthetic activity

Group

Time in minutes

Response in cm

Control (Before administration of the drug)

Standard drug (Xylocaine)

 

 

 

 

 

 

NS (reproduced)

Test (After administration of the drug) 1:10 concentration

 

 

 

NS (reproduced)

0

 

5

10

15

20

25

30

35

38

5

10

15

20

25

30

1.5+ 0.01

 

1.1+ 0.02

0.9 + 0.03

0.8 + 0.02

0.7 + 0.04

0.6 + 0.01

0.5 + 0.02

0.3 + 0.01

1.4 + 0.01

0.6+0.04

0.5+ 0.02

0.4+0.01

0.3+ 0.01

0.1 +  0.02

1.2 + 0.01

 

 

Table No.3: Infiltration method: Comparison between standard and test drug for local anesthetic activity:

Group

Time in minutes

Squeak Response

Before administration of the drug

Standard drug (Xylocaine)

 

 

 

 

 

 

 

 

 

Test(After administration of the drug)1:10 concentration

 

 

 

 

 

 

 

 

0

 

1

5

10

15

20

25

30

35

40

 

1

5

10

15

20

25

27

30

32

+

 

+

-

-

-

-

-

-

-

+

 

+

-

-

-

-

-

-

- +

+

 

In Muscle twitch method, control shows height of response (normal animal) of 1.5 cm and after administration of the test drug, the height gradually decreased up to 25 minutes. The test drug (1:10) concentration exhibited local anaesthetic activity. So, the duration of local anaesthetic activity was found to be 25 minutes.

 

In the Infiltration method, before administration of the drug, there was response for pin prick up to 1 minute. After administration of the test drug (1:10) concentration, there was no response for pin prick up to 27 minutes. The test drug (1:10) concentration exhibited marked activity when compared with standard drug(Xylocaine). So, the duration of local anaesthetic activity was found to be 27 minutes.

 

CONCLUSION:

From the above observation, we conclude that the onset of action of time was 5 minutes for 1:10 concentration in Nerve block method. The duration of local anaesthetic activity in muscle twitch and infiltration method for 1:10 concentration was approximately 25 and 27 minutes respectively.The local anaesthetic activity of C.gigantea was significant when compared with standard (Xylocaine). In future, further studies will be performed for isolation of the particular phytoconstituent which is responsible for local anaesthetic activity.

 

ACKNOWLEDGEMENT:

The authors are thankful to Smt. P. Sulochana, M.A., B.Ed., L.L.B, Chairperson, Dr. D. Ranganayakulu, Principal, Dr. D. Sujatha, B. Pushpakumari and C. P. Pullaiah, SPSP, Tiruchanoor, Tirupati for providing us facilities and helping us to carry out this research work.

 

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Received on 08.02.2010

Accepted on 16.03.2010     

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Research J. Pharmacology and Pharmacodynamics 2(2): March –April 2010: 178 -180