Evaluation of Wound Healing Potential of Ethanolic Extracts of Various Parts of Phyllanthus simplex Retz.

 

 

Arasan Elayaraja1*, M Vijayalakshmi2 and Devalarao Garikapati1

1KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada-      520 010, Andhra Pradesh, India.

2Department of Microbiology, Acharya Nagarjuna University, Acharyanagar, Guntur, Andhra Pradesh, India.

 

 

ABSTRACT

Wound healing is a complex dynamic process that results in the restoration of anatomic continuity and function. The present study has proved that the wound healing potential of ethanolic extract obtained from roots of Phyllanthus simplex Retz showed a significant effect than the same extract obtained from other parts of the plant. That extract showed a facilitatory epithelisation and wound contraction than other parts extracts. The root extract animal groups showed a high collagen content than other extracts and the control groups. Hexosamine content and ascorbic acid levels showed an increased level of the extract. Ascorbic acid is reported to have scavenging activity and inhibition of lipid peroxidation, which helps to show a better healing effect for the test groups.

 

KEYWORDS: Wound healing, Collagen, Hydroxy proline, Hexose amine, Epithelization.

 

INTRODUCTION:

Phyllanthus simplex Retz. is commonly called as “ Kaya-an”, “Bhuiamali  and  Kayut-bulang”. (Fam: Euphorbiaceae). It is a glabrous twining perennial herb, which has a taproot and its branches are compressed. Its flowers are solitary and its leaves are distichous. The siddha and ayurvedhic form of medications text showed that the Hindus used equal parts of the fresh leaves, flowers, fruit and cumin seeds with sugar, made into an electuary for the treatment of gonorrhea by taking a teaspoonful for twice a day. The fresh leaves, bruised and mixed with buttermilk, make a wash to cure itches in children. The root is used in Chota Nagpur as an external application for abscesses1-3.

 

Many Indian indigenous plants have a very important role in the process of wound healing. Those plants are more potent healers because they promote the skin repair mechanisms in natural way. Wounds cause the activation of a cytokine cascade that result in the formation of oxygen free radicals to lipid per oxidation. Any drug that shows inhibition of lipid peroxidation is believed to increase the viability of cells by improving circulation, preventing cell damage, promoting DNA synthesis, increase in tensile strength of collagen, increases lysyl oxidase formation, contraction of the wound and showing null effect of necrosis have excellent wound healing activity 4-7.

 

The present study is undertaken to investigate the wound healing activity of ethanolic extracts obtained from various parts of Phyllanthus simplex Retz.

 

MATERIALS AND METHODS:

Collection of Plant material:

Fresh whole plant materials of Phyllanthus simplex Retz had been collected from Chota-Nagpur of Jharkhand and was identified and authenticated by Dr. S. M. Khasim, Asst. Professor, Department of Botany, Acharya Nagarjuna University, Guntur.


One of the plant specimen had been planted in KVSR Siddhartha College of Pharmaceutical Sciences Vijayawada and a voucher (No: PS/PCRL/No: 0041/BN) had been deposited after planted in the herbal garden.

 

Preparation of Ethanolic extract:

The various parts of the plant material such as leaves including flowering tops, stem part closed with barks and roots had been separated and shade-dried. About 1kg of the milled powder of powdered parts was extracted successively with 95% ethanol (60-70°C) by Soxhlet apparatus and was concentrated under reduced pressure to semisolid consistency. Their yield and amount used for evaluation are given in table-1. A preliminary phytoscreening was also done to identify the presence of various phytoconstituents by using standard tests.

 

Preparation of Ointment Base:

About 35% of Bees wax was melted in a china dish using a water bath at a temperature of 60-80°C. Hot paraffin oil (5%) was also boiled in a water bath at the same temperature. Then transferred into the china dish with constant stirring using a glass rod. Finally 60% of petroleum gel was added and boiled for 15 minutes with constant stirring until the ointment base was cooled and semisolid in nature.

 

Experimental work:

The experiment protocol was duly approved by Institutional Ethical Committee.  Adult wistar rats of either sex (200-250gms) were procured from King’s Institute of Technology and Vaccination (Regd. No. -993/a/06/ CPCSEA). They were maintained for 12hrs light / dark cycle at an ambient temperature and fed with chow pellets (Hindustan lever) and water ad libitum. The animals were grouped into 6 batches with 4 animals per group.

Group I    Wound control (WC)

Group II    Wound + ointment prepared from Flowering tops and leaves extract (WFTLE)

Group III   Wound + ointment prepared from Stem bark extract (WSBE)

Group IV   Wound + ointment prepared from Root extract (WRE)

Group V    Wound + ointment prepared from Standard drug –Soframycin (WSDS)

 

Wound Creation:

A steel rod of diameter 2.5cm was heated to 80-85°C and burn wounds were created on the dorsal side of the rat. After 24h, dead tissues were excised using surgical blade and the wound was sterilized with surgical spirit. Control rats were dressed with paraffin and gauze. The tested groups were treated with formulation. 1gm of each formulation was used to treat the wounds. A similar quantity of soframycin was used to treat the Group-V animals. All the rats were kept under an observation period of 20 days. The rate of wound contractions was also monitored by measuring the wound areas for every 5days until the healing of the wound. The contraction was studied by tracing the raw wound area on a tracing sheet and measured. Its diameter was recorded.

 

Collection of Granulation tissue:

Granulation tissues were collected from both control and drug treated rats and washed with cold saline (0.9%w/v NaCl) to remove blood tissues and stored for analyzing various parameters such as collagen and hexosamine after lyophilized.

Blood sample:

The blood samples were collected by decapitation in the cervical region using a sterile syringe rinsed with EDTA. Then the plasma was separated from blood by centrifugation for 15 minutes at 1500rpm. The plasma was subjected for estimation of malondialdehyde and ascorbic acid.

 

Evaluation of Biochemical Parameters:

1. Hydroxy Proline: 8

Samples of varying concentrations were taken for analysis. Hydroxy proline was oxidized by adding 1ml of chloramine T to each tube. The contents were mixed thoroughly by shaking and allowed to stand for 20minutes at room temperature. Then 1ml of 70% perchloric acid was added to each tube for destruction of chloramines T. The contents were mixed and allowed to stand for 5minutes. Finally 1ml of PDAB (Para dimethyl amino benzaldehyde) solution was added and the mixture was shaken well. The colour developed was read by UV spectrophotometer (JASCO-Japan) at an absorbance of 530nm. The collagen content was then calculated by multiplying the hydroxy proline by the factor 7.46 and was expressed as mg/100mg of dry weight of the sample.

 

2. Hexose amine:9

Samples of various extracts were taken for analysis. The solutions were treated with 1ml of freshly prepared 2% acetylacetone in 0.5M Na2CO3 in capped tubes and kept in boiling water bath for 15 minutes. After cooling in tap water, 5ml of 95% ethanol and 1ml of Ehrlich’s reagent were added and mixed thoroughly. The purple red colour formed was read by UV spectrophotometer (JASCO-Japan) at 530nm after 30 minutes.

 

3. Malondialdehyde:10

To 0.1ml of the supernatant liquid 0.9ml of 10% TCA (Trichloroacetic acid) and 2.0ml of 67% thiobarbituric acid reagent were added and kept in boiling water bath for 20minutes. The tube was cooled after centrifugation and the mixture was measured at 532nm by UV spectrophotometer.

 

4. Ascorbic acid:11

To 0.5ml of plasma, 0.5ml of ice cold 10% TCA was added and mixed thoroughly and centrifuged for 20 minutes. About 0.5ml of the supernatant was mixed with 0.1ml of DTC reagent, mixed well and incubated at 37°C for 3hours. Then 0.75ml of ice-cold 65% conc. H2SO4 was allowed to stand at a room temperature for 30minutes. The yellow colour was read at 520nm by using UV spectrophotometer. Ascorbic acid was used as a standard.

 

Statistical Analysis:

All the results were expressed as mean ± SEM. P<0.05 was considered statistical significant.

 

 

Table 1: Amount of extract obtained and quantity of extract used for the observation

S. No

Parts Used

Amount yield w/w

Quantity used

1.

Flowering tops and leaves extract

0.425

40%extract

2.

Stem bark extract

0.724

40%extract

3.

Root extract

1.235

40%extract

 


Table 2: Various groups of animals showing the wound contraction during treatment period

S. No

Days

Group I

Group II

Group III

Group IV

Group V

1

0

4.97±0.004

4.97±0.004

4.97±0.004

4.97±0.004

4.97±0.004

2

5

4.02±0.032

4.17±0.042

3.86±0.014*

3.78±0.019*

3.98±0.012

3

10

3.71±0.023

3.28±0.0042

2.97±0.088*

2. 43±0.79*

2.36±0.0092

4

15

2.98±0.076

2.75±0.032

2.14±0.043*

1.75±0.043*

1.84±0.015

5

20

1.35±0.014

2.14±0.069

1.74±0.014*

0.96±0.065*

1.23±0.069

Values are mean ± S.E.M. (n = 4), *P<0.05 statistically significant when compared with control group.

 

Table 3: Biochemical parameters observed from various control, extract treated (3 various extracts) and standard groups

Biochemical Parameters

Group I

Group II

Group III

Group IV

Group V

L-Hydroxy proline

0.126± 0.0048

0.156 ± 0.0013

0.183 ± 0.0045

0.207 ± 0.0017*

0.224 ± 0.0021

Hexosamine

0.0413 ± 0.0017

0.0672 ± 0.0021

0.0972 ± 0.0031

0.1132 ± 0.0078*

0.1242± 0.008

Malondialdehyde

6.429 ± 0.0039

5.321 ± 0.0014

4.45 ± 0.0021

3.321 ± 0.0034*

2.231 ± 0.0056

Ascorbic acid

5.34 ± 0.013

4.2 ± 0.104

5.19 ± 0.104

8.3 ± 0.104*

9.2 ± 0.054

 

 

 

 

 

 

 

Values are mean ± S.E.M. (n = 4), *P<0.05 statistically significant when compared with control group.

 

 


RESULTS AND DISCUSSIONS:

The wounds treated with plant extracts showed a higher rate of wound contraction and they are significant to soframycin. Also the extracts obtained from roots are showing an increase in the wound contraction. The rate of contraction of the wounds increased with treatment showed an appreciable decrease in wound size as showed in table-2. The tensile strength of the collagen fiber was found to increase in tensile strength and hence showed an increase in biochemical parameters showed by the ointment prepared from Root extract treated animals (Group IV) as showed in table-3.

 

Hexose amine content in group IV animals indicate that the fibroblasts actively biosynthesized, ground substances on which the collagen can be laid on12. The cytokine cascade activated after a burn injury with stimulation of phagocytic cells that result in the formation of oxygen free radicals and lipid peroxidation. The control group showed an elevation in the lipid peroxidation levels which indicates the decreased free radical scavenging capacity of the wounded tissues. Lipid peroxidation is oxidative deterioration of PUFA. It leads to cell injury leading to generation of peroxides and lipid peroxides. Ascorbic acid was used as a standard drug for scavenging activity. In the present study it was found that the ascorbic acid levels were higher in the test group when compared to the control group and hence a decline in the lipid peroxidation.

 

Finally the present study showed that the wound healing potential of the root extract showed the significant results with the standard drug soframycin. Though many synthetic medications are available for the treatment of wounds these natural sources would serve better in the treatment of wounds at a faster rate.

 

REFERENCES:

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2.     Agarwal V.S. In: Drug Plants of India, Kalyani Publications, 1st edn., 2006; 2: 555.

3.     Rajkishor.S.N. and Thawra M.F. Phytochem 1988; 27 (9): 3027-3028.

4.     Nadiga Shoba. Ind J Pharmacol 1999; 31: 1 and 77.

5.     Khan M, Patil P A and Shoba J C. J Nat Remedies 2004; 4:1.

6.     Udayan P S, Satheesh George K V, Tushar and Indira Balachandran. J of Nat Remedies 2005; 5: 1.

7.     Prashant S Hegde, Anitha B and T S Chandra. Ind J Exp Biol 2005; 43: 3.

8.     Woessner J F Jr. Biochem J 1961; 83: 304-314.

9.     Elson L A and Morgan W T J. Proc Soc Exp Biol 1933; 58: 97-100.

10.   Yagi K. In: Assay for blood plasma or serum methods in Enzymology, 1984; 105: 328-331.

11.   Omayer et al, In: selected methods for the determination of ascorbic acid in animal cell tissues and fluids methods in Enzymology 1979; 62: 3-8.

12.   Karthikeyan J and Rani P.Ind J Exp Biol 2003; 41: 135-140.

 

 

Received on 08.10.2009

Accepted on 30.11.2009

© A&V Publication all right reserved

Research Journal of Pharmacognosy  and Phytochemistry. 2(1): Jan.-Feb. 2010, 34-36