Activities of carica papaya




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Rajampeta.

Editor,

Trees for life journal. 13.5.09

Respected sir,

Sub: Sending Review article for publication-req-reg.


We are very happy to send review article on current topic PHYTOCHEMICALCONSTITUENTS AND PHARMACOLOGICAL

ACTIVITIES OF CARICA PAPAYA L.” to your reputed journal for the purpose of publication. In this regard we are confirming that this manuscript has not been submitted to any other journal for publication.
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Yours faithfully,


R.Venkatalakshmi M.Pharm, C. Sasikala M.Pharm,

Dept.of Pharmaceutics , Dept of Pharmacology,

Annamacharya College of Pharmacy, Annamacharya College of Pharmacy, Rajempeta, kadapa Dt, A.P Rajempeta, kadapa Dt, A.P.

Parameshwar K, Mahesh kumar K

Annamacharya College of Pharmacy Annamacharya College of Pharmacy,

Sastra University, Rajempeta, kadapa Dt, A.P.

Rajempeta, kadapa Dt, A.P
Dr. C. Madhusudhana Chetty M.Ph., M.B.A., Ph.D.,

Principal,

Annamacharya College of Pharmacy,

Rajempeta, kadapa Dt, A.P.


*Correspondent author,
C. Sasikala,

Dept.of Pharmacology,

Sastra University,

Thanjavur-613 402.

Tamilnadu, India

hasipharm@gmail.com Phone: 09703652828.

PHYTOCHEMICAL CONSTITUENTS AND PHARMACOLOGICAL

ACTIVITIES OF CARICA PAPAYA L.

SASIKALA C*, VENKATALAKSHMI R, PARAMESHWAR K, MAHESH KUMAR K, MADHUSUDHANA CHETTY C.




Annamacharya College of pharmacy, Rajempet, Kadapa-516 216

Andhra Pradesh, India.

PHYTOCHEMICAL CONSTITUENTS AND PHARMACOLOGICAL

ACTIVITIES OF CARICA PAPAYA L.

ABSTRACT:
Many of the plants extracts have proven to possess pharmacological action. Carica papaya L. a plant widely used in the traditional medicinal system of India. It has been reported to possess analgesic, heart tonic, anti inflammation, anthelminitic and to treats ringworm, high blood pressure, stomachache, skin sores, fungal infections, jaundice, rheumatism, psoriasis, ringworm and also used for removal of cancerous growths, abortifacient, counter-irritant, amoebicide, dyspepsia, externally to burns and scalds. This review highlights some of the phytochemical and pharmacological aspects.
Key words: Carica pappya L. phytochemical constituents, pharmacological activities.

INTRODUCTION:
Carica papaya (Family Caricaceae) is an unbranched tree, about 8 cm in height. It is sometimes called "big melon" or "pay paw,”. Mostly it is cultivated practically all over the tropical & subtropical countries of the world particularly in Srilanka, India, Philippines, East Equatorial Africa, South America and West India (1). It is an interesting tree in that the male and female parts exist in different trees. The fruits, leaves, and latex are used medicinally. Papain, a major compound in the fruit and latex has been used in brewing and wine making and the textile and tanning industries.

It is known as Papaw or papaya tree in English, Popaiyah in Hindi, Papeya in Bengali, papai in Gujarathi, Arand-kharpuza in Punjabi, Kappalam in Malayalam, Poppayi in Tamil, Bappayi in Telgu (2). Latex used in psoriasis, ringworm, and prescribed for the removal of cancerous growths in Cuba (3). The juice is used for warts, cancers, tumors, corns, and indurations of the skin. The root infusion is used for syphilis in Africa and also used as analgesic. Leaf smoked for asthma relief in various remote areas. Javanese believe that eating papaya prevents rheumatism. Flowers have been used for jaundice. The leaves are used as a heart tonic, analgesic, and to treat stomachache. Carpine administered s.c or i.p in low dose (1.0to5.0 mg/kg) to mice, rats and rabbits caused dilation of skin blood vessels, hypotension and cardiac stimulation. Dose> 10.0 mg/kg showed opposite effects. Carpine (1.0 to 5.0 mg/kg I.V) induced myocardial ischemia. Carpine showed anti-microbial activity against Gram (+) ve and Gram (-) ve bacteria. A number of medicines like “papita forte” are produced from its fruits used for hepatics and insomnia (4).



PHYTOCHEMICAL CONSTITUENTS:
Per 100 g, the green fruit is reported to contain 26 calories, 92.1 g H2O, 1.0 g protein, 0.1 g fat, 6.2 g total carbohydrate, 0.9 g fiber, 0.6 g ash, 38 mg Ca, 20 mg P, 0.3 mg Fe, 7 mg Na, 215 mg K, 0.02 mg thiamine, 0.03 mg riboflavin, 0.3 mg niacin, and 40 mg ascorbic acid. Ranges reported for the ripe fruit are 32-45 calories, 87.1-90.8 g H2O, 0.4-0.6 g protein, 0.1 g fat, 8.3-11.8 g total carbohydrate, 0.5-0.9 g fiber, 0.4-0.6 g ash, 20-24 mg Ca, 15-22 mg P, 0.3-0.7 mg Fe, 3-4 mg Na, 221-234 mg K, 0.03-0.04 mg thiamine, 0.03-0.05 mg riboflavin, 0.3-0.4 mg niacin, and 52-73 mg ascorbic acid. Per 100 g, the leaves are reported to contain 74 calories, 77.5 g H2O, 7.0 g. protein, 2.0g fat, and 11.3 g total carbohydrates 1. 8 g fiber, 2.2 g ash, 344 mg Ca, 142 mg P, 0.8 mg Fe, 16 mg Na, 652 mg K, 0.09 mg thiamine, 0.48 mg riboflavin, 2.1 mg niacin, and 140 mg ascorbic acid, as well 136 mg vitamin E. Leaves contain the glycoside, carposide, and the alkaloid, carpaine. Flath and Forrey (1977) identified 106 volatile components in papaya (5). Fermentation with brewer's yeast and distillation yielded 91.8% was ethanol, 4.8%.methanol, 2.2% N-propanol, and 1.2% unknown (non-alcohol) (Sharma and Ogbeide, 1982) (6). As per USP specification papain contains not less than 6000 units per mg. Papain has proteolytic activity and hydrolyses polypeptides and amides and also it contain alkaloids, butanoic acid, methyl butanoate, carpaine, dehydrocarpaines, pseudocarpaine, chymopapain-a&b, flavonols, benzylglucosinolate, cis-and trans-linalool oxide, linalool , alpha-linolenic acid, nicotine, alpha-phellandrene, alpha-terpinene, gamma-terpinene4-terpineol,Terpinolene, methyl-thiocyanate and benzyl isothiocyanate, Myristic, palmitic, stearic, oleic, and linoleic acids. Pappya leaves contained a mixture of 95% chlorophylls a and b and also carotenoids (7,8). Xanthophylls, hydrocarbon

carotenoids and carotenol fatty acid esters were separated and identified from the papaya extract without saponification (9).



PHARMACOLOGICAL ACTIVITY:
Antioxidant
The oral administration of dried papaya juice to rats for 2 weeks at doses of 100,200 and 400 mg/kg exhibited antioxidant activity. In vitro evaluation of antioxidant effects of papaya showed that the highest antioxidant activity (80%) was observed with a concentration of 17.6 mg/kg (10).
Wound healing activity
The aqueous extracts of green papaya epicarp (GPE) and ripe papaya epicarp (RPE) were applied on induced wounds on mice. GPE treatment induced complete healing in shorter periods (13 days) than that required while using RPE (17 days), sterile water (18 days) and Solcoseryl ointment (21 days) ( 11). Nayak SB et al., results suggest that the aqueous extract of C. papaya fruit (100 mg kg (-1) day (-1) for 10 days) was evaluated for its wound healing activity in streptozotocin-induced diabetic rats using excision and dead space wound models. Extract-treated animals exhibited 77% reduction in the wound area when compared to controls which was 59% (12).

Antihypertension
The basal (control) mean arterial blood pressure (MAP) were 93.8 ± 4.5, 175.2 ± 5.1 and 181.3 ± 6.2 mmHg in the normotensive, renal and DOCA-salt hypertensive, respectively. Both hydrallazine (200 µg/100 g i.v) and extract (20 mg/kg.i.v) produced a significant

depression of MAP in all groups (p < 0.01 vs. controls), but the extract produced about 28% more depression of MAP than hydrallazine in the hypertensive groups (13).


Hypoglycemic effects
The extract of Carica papaya at 5.0 mg/kg produced significant blood glucose reduction with no significant reduction at the higher dose of 10 mg/kg (p>0.05).The leaf extract of Carica papaya significantly delays the onset of hypoglycemic activity of glimepiride, and increases the hypoglycemic effect of metformin with the variables interacting differently for each drug-extract combinations (14).
Hepatoprotective
The ethanol and aqueous extracts of Carica papaya showed remarkable hepatoprotective activity against CCl4 induced hepatotoxicity. The activity was evaluated by using biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, total bilirubin and gamma glutamate transpeptidase (GGTP) (15).
Anti inflammation
The anti-inflammatory activity of an ethanolic extract of Carica papaya leaves was investigated in rats using carrageenan induced paw oedema, cotton pellet granuloma and formaldehyde induced arthritis models. Experimental animals received 25-200 mg/Kg (orally) of the extracts or saline (control group) and the reference group received 5 mg/ Kg of indomethacin. The ulcerogenic activity of the extract was also investigated. The results show that the extracts significantly (p <0.05) reduced paw oedema in the carrageenan test. Likewise the extract produced significant reduction in the amount of granuloma formed from 0.58 +/-0.07 to 0.22 +/-0.03 g (16).

Antibacterial activity
The bioactive compounds of root extracts of Carica papaya L. were extracted, using water and organic solvents, and were investigated for antibacterial activity against some pathogenic bacteria using the cup plate agar diffusion method. The extracts are demonstrated higher activities against all the gram-negative bacteria than the gram (-) ve bacteria with the highest activity (14mm zone of inhibition) demonstrated against s. typhi. Carica papaya may be used for the treatment of gastroenteritis, uretritis, otitis media, typhoid fever and wound infections (17).

Miscellaneous activities
Immunomodulatory functions
Carica papaya seed extract is currently being marketed as a nutritional supplement with purported ability "to rejuvenate the body condition and to increase energy". The product claims to improve immunity against common infection and body functioning.
Enzymatic activity:
Papaya contains arginine, which is an amino acid that smoothes skin and aids in cell regeneration. Enzyme activity of ABS Pap-Ango Enzyme may be used in cleansers, facial masks, anti-aging creams, problem skin products, shampoo and conditioner as well as other hair care treatments.

Toxicity
Externally the latex is irritant, dermatogenic, and vesicant. Internally it causes severe gastritis. Some people are allergic to the pollen, the fruit, and the latex. Papain can induce asthma and rhinitis. In trials with rats, daily oral doses of benzene and alcohol extracts

(20mg/kg body weight (BW) for 30 days) did not effect body or reproductive organ weights or adversely effect liver or kidney function. However, aqueous extracts (1mg/kg BW for 7 or 15 days) and benzene extracts given orally to female rats caused infertility and irregular oestrous cycles. Male rats given ethanol seed extracts orally (10 or 50 mg/day for 30, 60, or 90 days) or intramuscularly (0.1 or 1.0 mg/day for 15 or 30 days) had decreased sperm motility. The oral doses also decreased testis mass and sperm count. Studies with aqueous seed extracts also decreased fertility in male rats. The fertility of the male and female rats returned to normal within 60 days after the treatments were discontinued (18).


CONCLUSION:
We conclude from the vast literature study, Carica papaya is a rich source of phytoconstituents mainly carpaine ,dehydrocarpaines ,pseudocarpaine.It has various traditional remedies and pharmacological activities like antioxidant, wound healing, hepatoprotective, anti inflammation, antibacterial, analgesic, heart tonic, anthelminitic and to treats ringworm, high blood pressure, stomachache, skin sores, fungal infections, cancer and prevents rheumatism, psoriasis.


REFERENCE:

1 Kalia AN (2005) Text book of Industrial pharmacognosy, 1 st edition, by A.N Kalia (Ed), Satish kumar Jain for CBC publishers& Distributors, NewDelhi. pp 24.


2. Nadkarni KM (2002) Indian meteria medica, popular prakashan private limited, Delhi. pp 273
3. Ram Rastogi P and Mehrotra BN (1990-1994) Compendium of Indian medicinal plants, volume 3, compendium of Indian medicinal plants. NewDelhi. pp 135-136.

4. Irfan Alikhan and Atiya Khanum (2007) Pharmaceutical wealth of fruits, vegetable & spices, 1 st edition: pp 88


5. Flath RA and Forrey RR (1977) Volatile components of papaya (Carica papaya L., Solo variety). J. Ag. & Food Chem 25(1): 103-109.
6. Sharma VC and ON Ogbeide (1982) Pawpaw as a renewable energy resource for the production of alcohol fuels. Energy 7(10):871-873.
7. Handa SS and VK Kapoo (2003) Text book of pharmacognosy by M K Jain for vallabh prakashan, Delhi: pp 240.
8.  Topuriya I (1990) Pigments of the plastids and flavonoids of the leaves of

Carica papaya. Chemistry of Natural Compounds 26 : 98-99

9. Pilar Cano Begona de Ancos M, M Gloria Lobo and Marianne Monreal (1999) Carotenoid Pigments and Colour of Hermaphrodite and Female Papaya Fruits ( Carica papaya L) cv Sunrise During Post-Harvest Ripening. Journal of the Science of Food and Agriculture 71(3):351-358.


10. Sanaz mehdipour, Nargesyasa, Gholamreza Dehghan, Reza khorasani, Azadeh mohammadirad, Roja Rahimi and Mohammed Abdollahi ( 2006) Antioxidant potentials of Iranian Carica papaya juice in vitro & in vivo are comparable to alpha tocopherol. phytotherapy research 20 (7):591-594.
11. Anuar NS, SS Zahari, IA Taib and MT Rahman (2008) Effect of green and ripe Carica papaya epicarp extracts on wound healing and during pregnancy. Food. Chem. Toxico 46(7):2384-9.
12. Nayak SB, L Pinto Pereira and D Maharaj (2007) Wound healing activity of Carica papaya L. in experimentally induced diabetic rats. Indian J Exp Biol 45(8): 739-43.
13. Eno E, Owo OI, E H Itam and Konya RS (2000) Blood pressure depression by the fruit juice of Carica papaya (L.) in renal and DOCA-induced hypertension in the rat. Phytotherapy Research 14 (4):235 – 239.
14. Fakeye TO, Oladipupo T, Showande O and Ogunremi T (2007) Effects of Co administration of Extract of Carica papaya Linn (family Cariaceae) on Activity of Two Oral Hypoglycemic Agents. Tropical Journal of Pharmaceutical Research 6: 671-678.
15. Rajkapoor Balasubramanian , Jayakar Balasundaram ,Kavimani Subramanian and Murugesh Narayanan (2002) Effect of dried fruits of Carica papaya L. on hepatotoxicity.

Biological & pharmaceutical bulletin 25: 1645-1646. 
16. Owoyele BV, Adebukola OM, Funmilayo AA and Soladoye AO (2008) Anti-inflammatory activities of ethanolic extract of Carica papaya leaves. Inflammopharmacology 16(4):168-73.
17. Doughari JH, Elmahmood AM, and Manzara S (2007) Studies on the antibacterial activity of root extract of carica papaya L. African journal of microbiology Research 1(3): 037-041.
18. Chinoy NJ ,Joshi Harsha, and Ghosh Shilpa (1997) Toxicity related response of female albino rats treated with benzene and alcoholic papaya seed extracts. Indian Journal of Environment and Toxicology 7 (2): 62-64.

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