Papaya juice, shoots and latex were used in Mayan herbal medicine and it has been in global use as both food and medicine. It has been cultivated since pre-Columbian times and was introduced to India and Europe in the 17th century.
Indigenous to Central America and Mexico, it is now naturalised in lowland tropical forests throughout the world and cultivated in gardens as a fruit and ornamental tree.
A fast-growing, short-lived, single-stemmed small tree, reaching up to 10m in height with a straight, cylindrical, soft, hollow grey trunk marked by leaf and inflorescence scars (Plate 16). The leaves are glabrous, deeply palmatifid, alternate, with long petioles and crowded at the apex of the trunk, forming a crown. Flowers are fragrant, trimorphous, usually unisexual and dioecious. Male flowers occur in loose, densely pubescent cymes, at the tip of the pendulous, fistular rachis. Female flowers are large, solitary or in sparse racemes, with a short thick rachis. The fruit is a large berry, variable in size, globose or elongated with a large central cavity. The seeds are black and enclosed in a transparent aril.
Milky juice, root, seeds, leaves and fruit pulp.
The fruit juice is regarded as a medicine in all countries where the tree is found and the milky juice of the unripe fruit is thought to possess powerful anthelmintic properties, particularly against roundworms. In southern India it is also believed to be an emmenagogue and the fruit is eaten to induce menstruation. The latex has been t applied to the neck of the womb to procure i abortion1 and a mixture of the root with the resin of Femia narthex is also used for that ? purpose. The powdered seeds are taken in northern India as an anthelmintic2 and their extract used as an antiinflammatory and- analgesic. In Nigeria the leaf extract and latex of the raw fruit are also taken to treat worm ? infestations.3 Other indications for which the plant is used include the ripe fruits as a diuretic and to treat flatulence4 and the latex for indigestion, colic, haemorrhoids and liver or spleen enlargement. Extracts of the flower or leaves are used as a febrifuge and heart tonic and a decoction of the inner stem bark for the treatment of dental caries.
The fruits are used as fodder. Fruit, leaves, latex and stem are used to treat indigestion, diarrhoea, swelling of the lungs, stoppage of urination, blindness, tachycardia, ringworm and alopecia.6 The seeds are used as anthelmintics.
The latex is a rich source of enzymes, including papain,' papaya glutamine cyclotransferase,s gl utaminyl- peptide cyclotransferase,9 chitinase, to chymopapain, caricain, glycyl endopeptidase," papaya peptidases A and B,12 a-D-mannosidase and N-acetyl-?-D-glucosaminidase.'3,'4 The fruit contains ?-galactosidases 1, II and III's and 1-amino cyclopropane-I-carboxylate (ACC) oxidase,'6 phenol- D-glucosyltransferase.
The fruit contains ?-carotene, cryptoxanthin, violaxanthin and zeaxanthin.,s,
The leaves contain carpi nine and carpaine, and the heartwood also contains pseudocarpaine.
4- Terpineol, linalool and linalool oxide are present in the fruit.
The shoots contain quercetin, myricetin and kaempferol.
The fruit contains calcium, potassium, magnesium, iron, copper, zinc and manganese.
Thiamine, riboflavin, niacin, ascorbic acid and a-tocopherol are present in the shoots.
Benzyl isothiocyanate has been isolated from the seed.
Antifertility activity: The antifertility effects of Carica papaya were investigated by feeding adult cycling and pregnant rats with different components of the fruit. No attempt was made to force-feed the animals and the results indicated that the unripe fruit interrupted the oestrus cycle and induced abortion. This effect decreased as the fruit became stale or ripe and exogenous progesterone partially counteracted this effect; the surviving foetuses were without distinct malformations.2s Adult male albino rats were administered 0.5 mg seed extract/kg body weight for 7 days and a significant reduction in total protein and sialic acid contents in both epididymal fluid and sperm pellet was observed. As compared with the control, lowered acid phosphatase activity was recorded in sperm pellet but higher levels in epididymal fluid after the treatment. The extract treatment also caused significant reduction in levels of inorganic phosphorus in the epididymal fluid.
The chloroform extract, benzene, methanol and ethyl acetate subfractions of the seeds were tested on sperm motility immediately after addition of the extracts and every 5 minutes thereafter for 30 minutes. Results showed that there was a dose-dependent spermicidal effect, showing an instant fall in sperm motility to less than 20%, and many of the spermatozoa became vibratory. Total inhibition of motility was observed within 20-25 minutes at all concentrations. Scanning and transmission electron microscopy revealed deleterious changes in the plasma membrane of the head and mid-piece of the spermatozoa. Sperm viability tests and estimations of abnormal spermatozoa suggested that they were infertile. Effects were spermicidal rather than spermiostatic, as revealed by sperm revival test. Contraceptive effects of the benzene fraction were reported in male albino rats. Body weight, weight of testis, epididymis, seminal vesicle and ventral prostate remained unaltered during the entire course of the investigation. Total suppression of cauda epididymal sperm motility coincided with a decrease in sperm count, viability and an increase in percentage of abnormal spermatozoa over 60-150 days. Minor changes in germ cell proliferation in the testis and vacuolisation and pyknotic nuclei in a few epithelial cells of the cauda epididymis were observed. Histology and biochemical composition of the testis and accessory sex organs, haematology and serum clinical biochemistry and serum testosterone levels remained unchanged throughout the course of the investigation. Tests also indicated mild oestrogenicity and monthly fertility tests revealed negative fertility. All altered parameters returned to normal levels 60 days following withdrawal of the treatment. These results suggested antifertility effects without undue adverse toxicity and that the effects may be directly rendered on the permatozoa.
Contraceptive efficacy, reversibility and toxicity of various fractions of the chloroform extract of the seeds were investigated in adult male rabbits at a dose regimen of 50 mglamimaVdayfor 150 days of treatment. Body weight, semen analysis, haematology, serum clinical biochemistry and the fertility status of control and treated animals were evaluated in the study. The chloroform and ethyl acetate chromatographic fractions did not produce appreciable changes in these parameters; however, the benzene fraction resulted in uniform azoospermia after 15 days of treatment, which was maintained for the remainder of the ISO-day observation period. The levels of fructose, glycerophosphocholine, acid phosphatase and lactate dehydrogenase in the seminal plasma were within the control range. Haematology and the serum clinical parameters showed no appreciable changes, indicating a lack of toxicity. The libido of the treated animals appeared to be normal although the fertility rate was zero. Normalcy of altered parameters was observed 60 days following withdrawal of treatment. It was concluded that this fraction of the seeds possesses reversible male contraceptive potential and the effects appear to be mediated through the testis.
In another experiment, a crude aqueous extract of Carica papaya seeds was studied on semen profile, fertility, body and organ weight response and toxicology, in male albino rats. Cauda epididymal sperm motility and count were reduced significantly at low and high dose regimens, for both oral and intramuscular administration. Reduced sperm motility was associated with morphological defects. Testicular sperm counts were also reduced in all treatment groups except for the low-dose intramuscular group. Fertility tests showed a dose- and duration-dependent reduction, with zero fertility observed at high-dose regimens. Testicular weight was reduced in all treatment groups, whereas accessory sex organs showed a variable effect. Body weight and toxicological observations did not reveal any untoward response and fertility and associated changes returned to normal within 4S days of treatment cessation. The antifertility effect of pawpaw seeds on the gonads of male albino rats was also demonstrated using an oral dose of 100 mglkg body weight administered orally for 8 weeks. A degeneration of the germinal epithelium and germ cells, a reduction in the number of Leydig cells and the presence of vacuoles in the tubules were observed.
Short-term administration of an aqueous extract of the seed manifested an androgen-deprived effect on the target organs and thereby caused the antifertility effect in adult male albino rats. The complete loss of fertility was attributed to a decline in sperm motility and alteration in morphology, as well as reduced contractile response of the vas deferens. The extract caused a slight alteration in the his to architecture and weight of the reproductive organs, mainly cauda and distal vas deferens. This appeared to be related to their greater androgen sensitivity in comparison to the other target organs or a diminished response to testosterone and its metabolites. Functional sterility was induced in male rats by the treatment, which shows potential as a male contraceptive.
An aqueous extract of Carica papaya seeds (S mg/kg/day 1M and 20 mg/kg/day PO) was investigated in male mice treated for 60 days. Reversibility studies were carried out to see if the effects were transient. The extract did not manifest oestrogenic effects in male mice and Lose studies indicated it to be non-toxic. Total body weight and weights of the reproductive organs, kidney and adrenal glands were not affected and serum SGOT, SGPT, protein and cholesterol levels remained within the normal range in the treated mice, suggesting that liver function and cholesterol and protein metabolism were not influenced by the extract.
The chloroform extract of the seeds has also been screened for hormonal properties using ovariectomised female rats to test for oestrogenicity, oestrogen-primed immature rats to test for progestogenicity and castrated adult male rats to test for androgenicity. The results revealed that the extract lacked progestogenic and androgenic effects, but did possess mild oestrogenic activity. An increase in weight of the vagina and uterus and presence of cornified epithelial cells in vaginal smears were observed, together with hypertrophy of the uterine epithelium, endometrium and stroma.
Uterotonic activity: Papaya latex extract (PLE) was tested on rat uterine preparations in vitro at various stages of the oestrus cycle and gestation periods. Uterine contractile activity was increased by PLE in the pro-oestrus and oestrus stages, rather than at the metoestrus and dioestrus stages. Maximum contractile activity was observed during the later stages of pregnancy, which corresponds to peak plasma levels of oestrogen. A direct, dose-dependent, spasmodic action with increased frequency and amplitude was observed with PLE in all non-gravid uterine preparations. Pretreatment of the tissue with phenoxybenzamine non-competitively inhibited the effect and blocking the 5-HT receptors with methylsergide partially inhibited the excitatory response to PLE. Pretreatment with indomethacin (a cyclooxygenase inhibitor) had no effect on the response. Mast cell degranulation (and subsequent release of heparin, biogenic amines or prostaglandins) was ruled out by pretreating the tissue with sodium cromoglycate, a mast cell stabiliser. Uterine contractions induced by pure papain were not sustained for a long period and at higher concentrations, the receptor proteins were denatured by its enzymatic action. From this study it appears that crude papaya latex contains a uterotonic principle, which may be a combination of enzymes, alkaloids and other substances acting mainly via the (X-adrenergic receptor population of the uterus at different stages.
Diuretic activity: Extracts of Carica papaya root, given orally to rats at a dose of 10 mg/kg, produced a significant increase in urine output (p < 0.01) comparable to that of hydrochlorothiazide and giving a similar profile of urinary electrolyte excretion. The analyses of urinary osmolality and electrolyte excretion per unit time suggested the observed effect may be a result of a high salt content of the extract.3s Hypotensive activity: Male albino Wistar rats were randomly divided into three batches (15 rats in each) of renal, DOCA-salt hypertensive and normotensive animals. Each batch was further divided into three groups: untreated, hydralazine-treated and extract-treated groups. The mean arterial blood pressure (MAP) and heart rate were measured in all groups. Both hydralazine (200 11g/100 g IV) and extract (20 mg/kg body weight IV) produced a significant depression of MAP in all groups (p < 0.01 v controls), but the extract produced about 28% more depression of MAP than hydralazine in the hypertensive groups. In another group of rats, the extract failed to depress the MAP in rats pretreated with propranolol, but atropine and noradrenaline pretreatment did not inhibit the action of the extract. In vitro studies using isolated rabbit arterial (aorta, renal and vertebral) strips showed that the extract (10 l1g/ml) produced a relaxation of vascular muscle tone, which was, however, attenuated by phentolamine (0.5-1.5 glml). It was concluded that the fruit juice contains antihypertensive agent(s), with mainya- fadrenoceptor activity.
Hypolipidaemic activity: Pectin from Carica papaya showed a highly significant hypolipidaemic activity in albino rats, mainly due to a lower rate of absorption and higher rate of degradation and elimination of lipids. Increased plasma lecithin cholesterol acyl transferase (LCAT) activity could account for the decrease in cholesterol levels and increased activity of lipoprotein lipase in adipose tissue and the heart may be responsible for the decreased concentration of triglycerides in serum of rats fed with pectin.
Antiulcerogenic activity: Effects on exogenous ulcers and histamine-induced acid secretion were studied in rats. The latex of the unripe fruit was effective in protecting against exogenous ulcer and significantly lessened acid secretion induced by histamine in chronic gastric-fistulated rats. Crystalline papain was also highly effective and the conclusion was that papain is the active principle exerting ulcer-protective effects.
Anthelmintic activity: Activity of papaya latex against Heligmosomoides polygyrus was demonstrated in experimentally infected mice. Five groups of BALB/C mice were infected with H. polygyrus (100 infective larvae per mouse). At day 22, four groups were given papaya latex suspended in water at dose levels of2, 4,6 and 8 g oflatex/kg body weight. One group served as non-treated controls. All animals were necropsied on day 25, that is, 3 days after treatment, for post-mortem worm counts. The latex showed a dose-dependent effect, suggesting a potential role for papaya latex as an anthelmintic, against patent intestinal nematodes in mammalian hosts.
In an investigation of the anthelmintic activity of papaya latex against infection of Ascaris suum in pigs, 16 naturally infected animals were allocated into four groups of four pigs on the basis of faecal egg counts and body weights. Three groups were given papaya latex orally at dose levels of 2,4 and 8 g of papaya latex per kg body weight and the fourth group served as a non-treated control. Results of worm counts on day 7 post treatment revealed reductions of approximately 40%,80% and 100% respectively. Some of the pigs receiving the highest dose of the latex showed mild diarrhoea on the day following treatment but otherwise, no clinical or pathological changes were observed.
Papaya seeds were extracted and fractionated and aliquots tested for anthelmintic activity using viability assays of Caenorhabditis elegans. Benzyl isothiocyanate (BITe) was found to be the predominant or sole anthelmintic agent in papaya seed extracts and is active against nematodes. Different parts of the plant were screened for in vitro anthelmintic activity against Ascaridia galli worms, which infect birds, and most were found to be more effective than piperazine. The mechanism of action of BITC was also compared to that of mebendazole (MBZ) using Ascaridia galli. Both BITC (100 and 300 uM) and MBZ (3 and 10 uM) inhibited glucose uptake and depleted glycogen content in the presence of glucose. However, neither had any effect on glycogen content of the worms in the glucose-free incubation medium. MBZ enhanced lactic acid production but BITC had variable effects and neither BITC nor MBZ had any effect on acetylcholinesterase activity of A. galli in vitro. BITC per se contracted the toad rectus muscle and enhanced frequency and magnitude of spontaneous contractions. It reduced the gross visible motility of A. galli after 20 hours of incubation, and in conclusion, the mechanism of action of BITC seems to lie both in inhibiting energy metabolism and affecting motor activity of the parasite.
Wound-healing activity: Pawpaw fruit is used by Jamaican nurses as a dressing for chronic skin ulcers and comments from them suggested that topical application of the unripe fruit promoted desloughing, granulation and healing and reduced odour in ulcers. It was cost effective and was considered to be superior to other topical application in the treatment of chronic ulcers. Although there was concern about the use of a non-sterile, non-standardised procedure, there were no reports of wound infection.
Fruit of Carica papaya is also used in the paediatric unit of the Royal Victoria Hospital, Banjul (The Gambia) as a major component of burns dressings. Cheap and widely available, the pulp of the papaya fruit is mashed and applied daily to infected burns. It appears to be effective in desloughing necrotic tissue, reducing infection and providing a granulating wound suitable for the application of a split-thickness skin graft. Possible mechanisms of action include the activity of the proteolytic enzymes chymopapain and papain, as well as an antimicrobial activity.
Antiamoebic activity: The seeds demonstrated in vitro antiamoebic activity."
Antifungal activity: The latex inhibited the growth of Candida albicans when added to a culture during the exponential growth phase. This fungistatic effect appeared to be the result of cell wall degradation, due to a lack of polysaccharidic constituents in the outermost layers of the fungal cell wall, and release of cell debris into the culture medium.
A mixture of Carica papaya latex (0.41 mg protein/ml) and fluconazole (2 }lg/ml) showed a synergistic action on the inhibition of Candida albicans growth. This synergistic effect manifested in partial cell wall degradation, as indicated by transmission electron microscopy.
Antimicrobial adivity: The flesh, seed and pulp of Carica papaya was shown by the agar-cup method to be bacteriostatic against several enteropathogens such as Bacillus subtilis, Enterobacter cloacae, Escherichia coli, Salmonella typhi, Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa and Klebsiella pneumoniae.'6Ripe and unripe fruits (epicarp, endocarp and seeds) were extracted separately and all produced significant antibacterial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomomas aeruginosa and Shigella jlexneri. The extracts were much more active against Gram-positive than Gram-negative bacteria:'
Antitumour activity: Flowers of Carica papaya showed strong in vitro antitumour-promoting activity when assayed by immunoblotting analysis of Raji cells carrying the Epstein-Barr virus (EBV) genome. The expresson of 'early antigens diffuse' (EA-D) and 'early antigens restricted' (EA-R) was determined by Western blotting of treated Raji cells with human sera of nasopharyngeal carcinoma patients. The extract was shown to suppress both EA-D and EA-R.'9 An ethanolic extract was screened in vitro for antitumour-promoting activity, using inhibition of EBV activation in l Raji cells induced by phorbol12-myristateB acetate and sodium-n-butyrate. It was found to be a strong inhibitor of EBV activation.
Free radical scavenging activity: Antioxidant '" action of a fermented papaya preparation. (PS-501) on free radicals and lipid peroxidation was evaluated using electron i spin resonance (ESR) spectrometry. The' preparation (50 mg/ml) scavenged 80% of hydroxyl radicals generated by Fenton reagents, with an ICso value of 12.5 mg/m!. Oral administration for 4 weeks decreased elevated lipid peroxide levels in the ipsilateral cerebrum 30 minutes after injection of iron solution into the left cortex of rats. It also increased superoxide dismutase activity in the cortex and hippocampus, suggesting antioxidant activity and a possible prophylactic effect against some age-related and neurological diseases associated with free radicals. PS-501 was investigated on DNA damage and tissue injury in the brain, formed during iron-induced epilepsy in rats. 8-Hydroxy-2' -deoxyguanosine (8-0HdG) is a major product of oxidative DNA damage. 8-0HdG levels in the ipsilateral cerebrum increased 30 minutes after iection of ferric chloride solution into the left sensory motor cortex of rats, but administration of PS-501 in drinking water prevented the increase of 8-0HdG levels in the cerebrum. It also inhibited the generation of nitroxide radicals in an image of the rat brain.
AJapanese health food, 'Bio-normaliser', prepared by the fermentation of Carica papaya, exhibited therapeutic properties against various pathologies including tumours and immunodeficiency. It efficiently inhibited the formation of oxygen radicals in cell-free systems and partly decreased spontaneous and menadione-stimulated superoxide production by erythrocytes, but manifested both stimulatory and inhibitory effects on oxygen radical release by dormant and activated phagocytes (neutrophils and macrophages). Bio-normaliser was able to enhance intracellular production of the innocuous superoxide ion and, at the same time, diminished the formation of reactive hydroxyl radicals, perhaps by inactivation of ferrous ion, the catalyst for the superoxide-driven Fenton reaction.
The seed and pulp were unequivocally demonstrated (by ESR spectrometry) to scavenge 1, 1-diphenyl- 2-picrylhydrazyl, hydroxyl and superoxide radicals. The seed gave the highest activity at concentrations (ICso) of2.1, 10.0 and 8.7 mg/ml, respectively and was comparable to that of soybean paste, miso, rice bran and baker's yeast. Vitamin C, malic acid, citric acid and glucose are thought to be possible antioxidative components in papaya.
Papaya is used as a food in most tropical regions of the world and no health hazards have been noted in conjunction with designated therapeutic dosages. Papaya is contraindicated in pregnancy because of the uterine and antifertility effects. There is a possible interaction with warfarin and large quantities should be avoided in coagulation disorders. Allergic reactions have also been documented. The leaves are categorised Class 1 by the American Botanical Council, meaning that they are safe when used appropriately.54 Oral administration of papain up to 800 mg/kg did not adversely affect prenatal development in rats and did not cause signs of maternal toxicity.sS Ethanol/water (1: 1) extracts of the aerial parts, when administered intraperitoneally to mice, gave an LDso > 1.0 g/kg and a crude ethanol extract of the unripened fruit administered to mice intraperitoneally gave an LDso of 325.2 mg/kg.
Dried leaves: 60-120 mg Dried latex: 120-240 mg Seed powder: 0.5-1 g
Dosha: Pacifies kapha and vata. Ripe fruit pacifies pitta