Carica papaya L

Scientific Name

Carica papaya L. [1]

Synonyms

Carica citriformis J.Jacq. ex Spreng, Carica citriformis Jacq, Carica cubensis Solm, Carica hermaphrodita Blanco, Carica jamaicensis Urb, Carica jimenezii Bertoni, Carica mamaya Vell, Carica peltata Hook. & Arn, Carica pinnatifida Heilborn, Carica portoricensis Urb, Carica posopora L, Carica rochefortii Solms, Carica sativa Tussac, Papaya carica Gaertn, Papaya cimarrona Sint. ex Kuntze, Papaya citriformis (Jacq.) A. DC, Papaya communis Noronha, Papaya cubensis (Solms) Kuntze, Papaya cucumerina Noronha, Papaya edulis Bojer, Papaya hermaphrodita Blanco, Papaya peltata (Hook. & Arn.) Kuntze, Papaya rochefortii (Solms) Kuntze, Papaya sativa Tuss, Papaya vulgaris A. DC, Vasconcellea peltata (Hook. & Arn.) A. DC. [1]

Vernacular Name

English Papaya, pawpaw, melon tree [2]
Malaysia Papaya, betek, ketalah [2], kates [3], betik, tembi, petik [4]
China Fan mu gua [3][4], wan shou guo, mu gua, fan gua [4]
India Pappali, kai, papeeta, papiita (Hindi); karamoza, omakai, omakaya (Malayalam); papai, papaya, popai (Marathi) [2]; omita (Assamese); papaiya, papayi (Gujarati); katcha pepita (Punjabi); Esi (Samoa);papiitaa, pappeeta (Urdu) [3]
Bangladesh Pepe [3]
Indonesia Papaya, gedang (Sundanese); kates, gandul, katela gantung (Javanese) [2]
Philippines Papaya, kapaya, lapaya [2]
Myanmar Thimbaw [2]
Cambodia Lhong, doeum lahong [2]
Laos Houng [2]
Thailand Malakor (Central); loko (Peninsular); ma kuai thet (Northern)[3]; malakaw, lawkaw, tengton [4]
Japan Motukawa, papaia, popoo [3]
Korea Pa pa ya [3]
Vietnam Du du [2]
France Papayier, arbre de melon [2], papaya, papayer [3]
Germany Melonenbaum, papayabum [3]
Russia Papaia [3]
Italy Papaia [3]
Poland Melonoweic wlasciwy, papaja [3]
Spain Fruta bomba, lechosa, melon de arbol, melon zapote, papayero, papaya, papaya [3]
Portugal Ababaia, mamao, papaia, fruto de mamoeiro, papeira [3]
Czech Republic Papaja [3]
Estonia Harilil papaia, papaia [3]
Hawaii He’i, mikana, milikana [3]
Fiji Oleti [3]
Palau Babai,bobai [3]
Kenya Papai [3].

Geographical Distributions

Carica papaya L. is originated from Central America [2][5][6][7][8]. In 16th century, the Spaniards was brought it to the Caribbean and South East Asia [1] and then it continues spreading to India, Oceania and Africa. This plant grows in warm areas with adequate rainfall, in altitude from sea level up to about 1600 m [2]. C. papaya is easily adapted to the subtropical and tropical environment, today it can be found in most of these areas around the world [6].

Botanical Description

C. papaya is a fast-growing tree-like herb that can grow up to 2-10 m tall. It is usually unbranched but sometimes branched due to injury. It contains white latex in all parts. [2]

The stem is usually single-stemmed, indeterminate form of growth, branching at lower parts of the plant which is rarely exceeds a few centimeters in length [9]. The stem cylindrical, measures 10 cm in diametre, hollow with prominent leaf scars and spongy-fibrous tissue [2].

The leaves are large palmate measures approximately 0.6 m square. The leaf blade is extremely lobed with 5-9 pinnate lobes [9]. The leaves are spirally arranged and clustered at apex of the trunk. The shape of the leaves is orbicular, 25-75 cm in diameter, smooth and prominently veined. The petiole is up to 1 m long [2].

This plant is polymorphic which has three sex form; female, male and also hermaphrodite resulting of four types of flowers. Two are hermaphroditic types which are called as ‘elongata’ and ‘pentandria’ and the other two are unisexual types that are ‘staminate’ and ‘pistillate’. All flowers are borne on extremely short and stout pedicels. The flowers are arise axillary and each of the sex form is found on separate trees [2] [9] [10].

The male flower s is panicle, measuring 25-100 cm long, pendent and sessile. The calyx is in cup-shaped, small and 4-toothed. The corolla in trumpet shaped, 3.5 cm long with 5 spreading lobes and light yellow in colour . The stamens 10, exist in 2 whorls alternate with the petal lobes [2]. The female flowers is in solitary or in a few-flowered cymes measures 3.5-5.0 cm long. the calyx is in cup-shaped measuring 3-4 mm long with 5 narrow teeth. The corolla 5 and almost free petals, lanceolate, twisted, fleshy and yellow in colour. The ovary rounded and superior, 2.0-3.0 cm long, many ovules and central cavity existed. The stigma 5 with fan-shaped, sessile and deeply5-cleft [2] [9]. Lastly is the hermaphrodite flower that has 2 types; elongata and pentandria. Elongata flowers is in a short-peduncled cluster and has semi-united petals, the stamens 10 in 2 series with elongated ovary. Pentandria flowers is similar as female flowers but it has 5 stamens in addition. Sometimes, an intermediate flowers was occur in which the stamens become carpelloid resulting an irregular fruit [2].

The fruit is in a berries and show high variation in size and shape but generally ovoid-oblong to nearly spherical, pyriform or grooved with 7-30 cm long, weighing up to 10 kg with a thin skin, smooth and yellowish to orange colour in ripe fruit. The fruit edible, sweet with mild and pleasant flavour [2] [9]. The fruit shape in female plants tend to be round wheareas in hermaphroditic plants tend to be elongated with a shape vary from cylindrical to the pear shaped [9].

The seeds spherical measures 5 mm in diametre with a black or greyish in colour, numerous, with approximately 600 seeds or more in well-pollinated fruit. The seeds are attached in 5 rows to interior wall of ovary enclosed in a gelatinous sarcotesta. [2] [9]

Cultivation

No documentation.

Chemical Constituent

Aqueous extract of C. papaya leaves has been reported to contain phenolic compounds (e.g. ρ-coumaryl trimethyl glycoside, 5-hydroxy caffeoyl-O-glycoside, kaempferol 3-O-pentoside, feruloyl quinic acid, syringic acid hexoside, chlorogenic acid, kaempferol-3-O-rhamnoside, syringic-caffeic acid ester and sinapic acid-O-hexoside) [11]. Methanol extract of C. papaya leaves has been reported to contain phenolic compounds (e.g. 5,7-dimethoxycoumarin, protocatechuic acid, ρ-coumaric acid, caffeic acid, chlorogenic acid, kaempferol and quercetin) [12]. Ethanol, n-hexane, and chloroform extract of C. papaya leaves has been reported to contain steroids and quinones while only ethanol extract contains tannins and alkaloids [13]. C. papaya leaves also has been reported to contain flavonols (e.g. manghaslin, clitorin, rutin, and nicotiflorin) and piperidine alkaloids (e.g. carpaine, 6-(8-Methoxy-8-oxooctyl)-2-methylpiperidin-3-yl 8-(5-hydroxy-6-methylpiperidin-2-yl)octanoate, and 13,26-Dimethyl-2,15-dioxa-12,25-diazatricyclo[22.2.2.211,14]triacontane-3,16-dione). [14]

Aqueous extract of C. papaya seeds has been reported to contain phenolic compounds (e.g. syringic acid hexoside, 5-hydroxy caffeic quinic acid, 5-hydroxy feruloyl quinic acid, acetyl ρ-coumaryl quinic acid, feruloyl quinic acid, ρ-coumaryl trimethyl glycoside, kaempferol-3-O-rhamnoside, n-methyl feruloyl quinic acid, quercetin-3-O-glycoside, quercetin-3-O-rhamnoside, chlorogenic acid and cyanidin-3-O-glucose) [11]. Ethanol extract of C. papaya seeds has been reported to contain glyceryl­1­oleiyl­2,3­dilinoleiate, glyceryl­1­oleiyl­2,3­diarachidate, glyceryl­1­oleiyl­2,3­distearate, 2,3,4­trihydroxytoluene (caricaphenyl triol), carpaine, glyceryl­1,2­dipalmitate, glyceryl trimyristate, glyceryl tristearate, glyceryl­1,2­dipalmityl-3-myristate, glyceryl­1­oleiyl­2,3­di myristate, glyceryl­1­(2’,3’,4’­trihydroxybenzoyl)­2,3­dioleate (papayaglyceride), β­sitosterol glucoside, glyceryl­1­oleiyl­3­phosphate, glyceryl­1­oleiyl­2­lauryl­3­phosphate and glyceryl­1,2­distearyl­3­phosphate. [15]

Aqueous extract of C. papaya stems has been reported to contain phenolics (e.g. kaempferol-3-O-pentoside, chlorogenic acid, syringic-caffeic acid ester, n-ethyl-ρ-coumaryl quinic acid, 5-hydroxy caffeoyl quinic acid, peonidin-3-O-glucoside, feruloyl-O-hexoside, syringic acid hexoside, cyanidin-3-O-glucose, methyl feruloyl glycoside and feruloyl quinic acid). [11]

Aqueous extract of C. papaya roots has been reported to contain phenolics (e.g. quercetin-3-O-rhamnoside, chlorogenic acid, kaempferol-3-O-rhamnoside, feruloyl quinic acid and n-acetyl ρ-coumaryl quinic acid). [11]

Aqueous extract of C. papaya fruits has been reported to contain phenolic compounds (e.g. chlorogenic acid, feruloyl quinic acid, 5-hydroxycaffeoyl-O-glycoside, quercetin-3-O-glycoside, caffeoyl hexose deoxyhexoside, ρ-coumaroylquinic acid derivative and feruloyl-O-hexoside) [11]. C. papaya fruit skins extract has been reported to contain phenolic compound (e.g. ferulic acid, ρ-coumaric acid, and caffeic acid) [16].Its fresh slices and juices have been reported to contain carotenoids (e.g. α-carotene, lycopene, β-carotene, β-criptoxanthin, cryptoxanthin, and zeaxanthin), vitamin A and vitamin C. [16] [17]

C. papaya latex has been reported to contain a lipolysis enzyme (e.g. phospholipadase D) [18], and an esterase enzyme (e.g. carboxyl ester hydrolase). [19]

Plant Part Used

The sap, fresh or dried seeds, fruits, fresh leaves, roots and barks. [20][22]

Traditional Use

C. papaya has been used as a remedy for numerous maladies, ranging from gastrointestinal disorders to asthma and sexually transmitted diseases. Perhaps the most common use of C. papaya is that of an antihelmintic. Often, the plant is boiled along with herbal adjuvants in order to expel worms. [21]

Boiled extracts of the stem bark were usually given for urinary problems. Inner bark decoction shall be useful to soothe toothache by oral consumption while the stem bark paste can be applied to boils, burns and wounds to facilitate the healing process. [22]

C. papaya leaves have shown to treat internal parasites invasion when used in infusions. Whether decoction or infusion, they are consumed orally to treat high blood pressure, obesity and diabetes [23][24] and malaria (weak decoction) [21]. The juice of C. papaya leaves is used to treat amenorrhea while infusion of young leaves is used for fever [25]. The leaves of C. papaya can also be eaten raw to treat dengue fever and used for dressing wounds and injuries [26]. In Madagascar, a tea made of from C. papaya leaves has also been used in order to treat gastric ulcers as well as general gastric discomfort [27]. In Congo the leaves are left to dry before inhaled to treat bronchial asthma [20]. In rare circumstances, the infusion of the flowers can be used for its emmenagogue, febrifuge and pectoral properties [28].

The green fruit is applied on ringworm infestation by rubbing rigorously until the skin bleeds. The green immature fruits as well are tapped for papain. Once cut, the harden milky latex is used in preparation of meat tenderizers, digestive medicines, manufacture of chewing gum and even in textile industry, the latex helps prevent shrinkage of wool and silk [29] while the sap itself can be applied topically to treat toothache, corns and warts [22]. In Sierra Leone, the latex sap is drunk raw to treat jaundice. In DR Congo and Senegal, three to four spoonfuls of the latex sap shall be eaten on empty stomach or mixed with food to make a paste to treat worm infestations respectively [20]. The fresh fruit are administered for digestive conditions as it helps ease down constipation problems [22] and used as a diuretic as well as for stomach ache pain relief [21]. The whole fruit of C. papaya can also be used by boiling and used as an infusion in order to treat stomach ulcers [29].

The seeds are used as an oxytocic and externally as an antifungal agent as well as to expel worms [21]. Contrasting enough however, in Indian history of traditional medicine back in 16th century, the unripe and green fruit was made into curry and eaten by woman to stimulate the secretion of milk [28].

The papain tree roots can be used in various ways. Through decoction, it can ease bloody diarrhoea symptoms while through rubbing on the skin or scalp, the root is useful to lighten headache and dizziness traditionally [30]. The fresh root rubefacient is useful to relieve centipede bites, wounds and even snakebites [22].

The infusion of bark and root helps to treat gonorrhoea and syphilis [29], the combination of leaves and seeds can act against amebiasis and anthelmintic [21]. In a combination usage with the leaves of Azadirachta indica, C. papaya can be an excellent remedy for malaria through steam treatment [31].

Preclinical Data

Pharmacology

Antihyperglycemic activity

Aqueous extract of C. papaya leaves (0.75, 1.5 and 3 g/100 mL) administered orally to streptozotocin-induced diabetic male Wistar rats (250-300 g) for duration of 30 days significantly (p < 0.05) decreased the serum glucose level (250±1.02 mg/dL at 3 g/ 100 mL) in dose dependent manner compared to untreated diabetic rats (434±7.49 mg/dL). The extracts also significantly (p < 0.05) reduced the alanine aminotranferase (ALT: 61.16±2.9 U/L at 0.75 g/ 100 mL, 81.85±14.6 U/L at 1.5 g/100 mL), aspartate aminotransferase (AST: 169.5±4.8 U/L at 0.75 g/ 100 mL, 187.9±14.1 U/L at 1.5 g/100 mL) and alkaline phosphatase level (ALP: 441±10.6 U/L at 0.75 g/ 100 mL, 437.7±10.8 U/L at 1.5 g/100 mL, 642.6±11.6 U/L at 3 g/ 100 mL) compared to untreated diabetic control (ALT: 276 ± 16.6 U/L, AST: 345.5±10.4 U/L, ALP: 798.4±14.7 U/L). Meanwhile, the extract significantly (p < 0.05) increased the plasma insulin level (0.43±0.05 ng/dL at 0.75 mg/100 mL, 0.38±0.2 ng/dL at 1.5 mg/100 mL, 0.43±0.01 ng/dL at 3 g/ 100 mL) compared to untreated diabetic control (0.42±0.02 ng/dL). [32]

Alcohol (30%) extract of C. papaya leaves (100, 200 and 400 mg/kg) administered orally to alloxan-induced diabetic Wistar rats (150–200 g) for duration of 21 days significantly (p < 0.05) reduced the serum glucose level from two hour (400 mg/kg: 235.1±10.4 mg/dL), Day-7 (200 mg/kg: 242.4±4.8 mg/dL) and Day-14 (100 mg/kg: 170.7±5.8 mg/dL) compared to untreated diabetic control (at two hour: 266±5.1 mg/dL, Day-7: 280±1.2 mg/dL, Day-14: 293±2.2 mg/dL). [33]

Chloroform extract of C. papaya leaves (31, 62, and 125 mg/kg) administered orally to streptozotocin-induced diabetic adult male Wistar rats (250-300 g) for a duration of 20 days significantly (p < 0.05) decreased the blood glucose level (122.2±36.1 mg/dL at 31 mg/kg and 113.8±25.1 mg/dL at 62 mg/kg) compared to untreated diabetic rats (344.5±95.5 mg/dL). The extract also significantly (p < 0.05) reduced the alanine aminotranferase (ALT: 119.3±18.1 U/L at 31 mg/kg, 116.8±25.1 U/L at 62 mg/kg, 153.8±31.3 U/L at 125 mg/kg), aspartate aminotransferase (AST: 160.6±25.5 U/L at 31 mg/kg), 166.8±7.1 U/L at 62 mg/kg, ) and serum triacylglycerol level (TAG: 94.3±18.9 mg/dL at 31 mg/kg, 68.5±15.0 mg/dL at 62 mg/kg, 99.0±12.2 mg/dL at 125 mg/kg) compared to untreated diabetic control (ALT: 238.8±22.5 U/L, AST: 395.8±28.3 U/L, TAG: 180.5±12.5 mg/dL). Meanwhile, the extract only significantly (p < 0.05) increased the basal plasma insulin level in a non-diabetic rats receiving C. papaya treatment (1.90±0.26 ng/mL at 62 mg/kg) compared to control non-diabetic rats (1.06±0.12 ng/mL). [13]

Hypolipidemic activity

Aqueous extract of C. papaya leaves (0.75, 1.5 and 3 g/100 mL) administered orally to streptozotocin-induced diabetic male Wistar rats (250–300 g) for duration of 30 days significantly (p < 0.05) decreased the serum cholesterol (Chol: 57.37±2.9 mg/dL at 3 g/ 100 mL) and triglyceride level (TG: 146.8.9 mg/dL at 0.75 mg/100 mL, 144.5±11.6 mg/dL at 1.5 mg/100 mL, 93.71±17.2 mg/dL at 3 g/100 mL) compared to untreated diabetic control (Chol: 75.62±2.9 mg/dL, TG: 232.1±17.3 mg/dL). The extract showed a significant (p < 0.05) decreased in liver cholesterol (9.49±0.82 mg/g tissue at 3 g/100 mL) and TG level (55.40±4.64 mg/g tissue at 0.75 g/100 mL, 59.07±6.48 mg/g tissue at 1.5 g/100 mL, 56.47±2.43 mg/g tissue at 3 g/100 mL) compared to untreated diabetic control (Chol: 10.78±1.06 mg/g tissue, TG: 69.71±5.00 mg/g tissue). Meanwhile, the extract significantly (p < 0.05) increased the high-density lipoprotein (43.32 mg/dL at 1.5 g/100 mL) compared to untreated diabetic control (34.25±2.09 mg/dL). [32]

Alcohol (30%) extract of C. papaya leaves (400 mg/kg) administered orally to alloxan-induced diabetic Wistar rats (150-200 g) for duration of 21 days significantly (p < 0.05) reduced the cholesterol (135.32±4.04 mg/dL) and TG level (145.18±3.67 mg/dL) compared to untreated diabetic control (Chol: 153.88±4.19 mg/dL, TG: 189.86±1.74 mg/dL). [33]

Antioxidant activity

Hydroalcoholic (80%) extract of C. papaya leaves showed antioxidant activity with 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (inhibition concentration at 50% cell growth (IC50) of 80 µg/mL) compared to L-ascorbic acid (IC50 of 4.4 µg/mL) using DPPH scavenging assay, metal chelating activity (IC50 of 972.8 µg/mL) compared to ethylenediaminetetraacetic acid (IC50 of 9.6 µg/mL) using metal chelating assay and reducing power activity using reducing power assay. The total phenolic content was found to be 5.8±0.1 mg Gallic acid equivalence (GAE)/g while the flavanoid contents was 2.1±0.1 mg Catechin Equivalence (CE)/g). [34]

Aqueous extract of C. papaya leaves showed antioxidant activity with DPPH scavenging activity (IC50 of 60.2 µg/mL) using DPPH scavenging assay. [35]

Methanol extract of C. papaya leaves (2.00 mg/mL) showed antioxidant activity with hydroxyl scavenging activity (88%), hydrogen peroxide scavenging activity (45%), metal chelating activity (38%) and reducing ability (95%) compared to ascorbic acid (hydroxyl scavenging activity: 90%, hydrogen peroxide scavenging activity: 50%, metal chelating activity: 60%, reducing ability: 97%). The extract (0.25-2.00 mg/mL) also inhibited erythrocyte haemolysis (inhibition concentration at 50% of growth (IC50) of 7.33 mg/mL for haemolysis) and erythrocyte lipid peroxidation (IC50 of 1.58 mg/mL) compared to ascorbic acid (IC50 of 1.87 mg/mL for haemolysis, IC50 of 0.43 mg/mL for lipid peroxidation). [36]

Fractions (petroleum ether, ethyl acetate, n-butanol and water) of ethanolic extract of C. papaya leaves (3-50 µg/mL) showed reactive oxygen species (ROS) scavenging activity using Dichloro-dihydro-fluorescein assay. Petroleum ether fraction (25 µg/mL) showed highest lactate dehydrogenase (LDH) leakage protection (90%) in comparison to tert-butyl hydroperoxide-treated group using LDH leakage assay. Petroleum ether fraction (25 µg/mL) showed higher reduction (47%) of ROS when compared with α-tocopherol (17%). [37]

Fermented papaya preparation (FPP) (2.4 mg/mL) showed significant (p < 0. 05) high scavenging activity of reactive oxygen species (ROS) including hydroxyl free radical and superoxide anion with relative scavenging ability of cell supernatant of 0.32 and 0.65, respectively using fluorescence method in copper triggered the Aβ neurotoxicity in SH-SY5Y cells overexpressed in Swedish mutant form of human APP (APPsw) compared to non-treated cells (superoxide anion: 0.8, hydroxyl radicals: 0.21). Administration of FPP also reduced nitric oxide (NO) accumulation by 42.1%, and reduced inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) regulation by 43 % and 71 %, respectively. [38]

Ethanol extract of C. papaya leaves (50 and 200 mg/kg bw) was administered orally to lead-induced oxidative stress in male albino Sprague Dawley rats (160-180 g) for a duration 14 days. The extract showed antioxidant activity by significantly (p < 0.05) increased glutathione content (GC) and reduced protein carbonyl content (PCC) in the femur of the sacrificed rats in a dose dependant manner. [39]

Antiproliferative activity

Aqueous extract of C. papaya leaves (0.25-2.0%) inhibited growth of cervical carcinoma cell line (Hela), breast adenocarcinoma cell line (MCF-7), hepatocellular carcinoma cell line (HepG2), lung adenocarcinoma cell line (PC14), pancreatic epitheliod carcinoma cell line (Panc-1), mesothelioma cell line (H2452), T cell lymphoma cell line (Jurkat), plasma cell leukemia (ARH77), Burkitt’s lymphoma (Raji) and anaplastic large cell lymphoma (Karpas-299) in dose-dependent manner using [3H]- thymidine incorporation assay [40].

Cytotoxic activity

Aqueous extract of C. papaya leaves (0.125%) administered to human peripheral blood mononuclear cells (PBMC) showed cytotoxicity effect on chronic myelogenous leukemia cell line (K562) using [3H] - thymidine incorporation assay. [40]

Hepatoprotective activity

Hydroalcoholic (80%) extract of C. papaya leaves (0.5 µg/mL) significantly (p < 0.05) reduce the reactive oxygen species (40%) and increased glutathione peroxidase activity (glutathione content: 1.75 nmol/mg protein) in tert-butyl hydroperoxide (t-BOOH) induced-oxidative stress of human liver cells (HepG2 cells) compared to control (glutathione content: 3.6 nmol/mg protein). [34]

Gastroprotective activity

Aqueous extract of C. papaya leaves (500 mg/kg) was administered orally to male Sprague Dawley rats (180-220 g) 30 minutes before induction of gastric ulcer using ethanol. The extract significantly (p < 0.05) increased glutathione peroxidase level (GPx: 2.475±0.214 U/mg protein) while decreased the malonaldehyde level (MDA: 0.102±0.020 MDA/µmol/L) and mean ulcer index (993.6±141.384 mm2) compared to ethanol-induced control group (GPx: 2.229±0.281 U/mg protein, MDA: 0.133±0.019 MDA/µmol/L, mean ulcer index: 6235.2±386.33 mm2). [35]

Antimutagenic activity

Ethanol (96%) of C. papaya leaves (500 mg/kg) administered orally to female Wistar-Kyoto rats (100-250 g) for duration of 24 hours significantly (p < 0.05) decreased micronucleated polychromatic erythrocytes rate (MN-PCE: 1.6±0.5) compared to cyclophosphamide-treated control group (20±4.9) while increased the polychromatic (PCE) to normochromatic (NCE) ratio (PCE/NCE: 1.13±0.28) compared to distilled water treated group (PCE/NCE: 0.47±0.21). [41]

The extract administered orally to female Wistar-Kyoto rats (100-250 g) at 48, 36 and 24 hours before cyclophosphamide induction at 24 hours pre-euthanasia significantly (p < 0.05) decrease the PCE/NCE ratio (0.39±0.07) compared cyclophosphamide-treated control group (20±4.9). [41]

Antisickling activity

Hydroalcoholic extract of C. papaya leaves (5 mg/mL) was administered to sickle erythrocytes (SS cells) before induction of sickling using sodium metabisulphite (2%). The extract showed inhibition in the formation of SS cells (0-5% of SS cells) compared to untreated SS cells (60% of SS cells). The extract (3 mg/mL in 0.25% sodium chloride) also decreased the percentage haemolysis of SS cells (100-8% lysis) compared to untreated SS cells (50%). [42]

Immunomodulatory activity

Aqueous extract of C. papaya leaves (0.125 – 0.5%) reduce the production of Interleukin (IL)-2 and IL-4 while increased the IL-12p40, IL-12p70, interfereon-γ and tumour necrosis factor (TNF)- α in anti-CD3 and anti-CD28-treated human peripheral blood mononuclear cells. [40]

Fractions of crude extract of C. papaya seeds significantly (p < 0.001) enhanced the lymphocyte phytohemagglutinin responsiveness and inhibited the classical complement-mediated hemolytic pathway in mitogen-induced proliferative response of lymphocyte. [43]

Analgesic activity

Ethanol, ethyl acetate, and n-hexane extract of C. papaya leaves extract (0.175, 0.35, and 0.70 mg/kg body weight) administered orally to acetic acid-induced writhing in mice for a duration of 60 minutes showed a significant (p < 0.05) analgesic activity based on their whrithing behaviour. Ethanol extract (0.70 mg/kg bw) showed the best activity with 224 times writhing comparable to control aspirin (209) compared to non-treated control (501). [44]

Contraception agents

The methanol subfraction (MCP I) and ethyl acetate subfraction (ECP I) of chlroform extract of C. papaya seeds (50 mg/kg bw) administered orally to three months old Sprague Dawley rats (180-200g) each day for 360 days significantly decreased the total body weight (MCP I: 168±1.29 g, ECP I: 162±9.14 g) and weights of testis (MCP I: 520±5.57 mg/100 g bw, ECP I: 531±7.43 mg/100 g bw), epididymis (MCP I: 145±3.91 mg/100 g bw, ECP I: 143±4.86 mg/100 g bw), seminal vesicle (MCP I: 183±2.61 mg/100 g bw, ECP I: 181±2.31 mg/100 g bw) and ventral prostate (MCP I: 96±8.31 mg/100 g bw, ECP I: 98±5.37 mg/100 g bw) compared to control (MCP I: 190±2.24 g, 580±2.24 mg/100 g bw, 178±1.00 mg/100 g bw, 222±1.00 mg/100 g bw, 118±6.42 mg/100 g bw, ECP I: 181±1.89 g, 570±3.36 mg/100 g bw, 173±1.36 mg/100 g bw, 224±4.46 mg/100 g bw, 124±1.84 mg/100 g bw, respectively). Sperm characterisation showed a total inhibition in sperm motility and significant declined in sperm viability (MCP I: 9±0.45 %, ECP I: 9±2.91 %) and sperm density (MCP I: 3±1.40 million/mL, ECP I: 3±2.39 million/mL), while increased in abnormal sperm (MCP I: 87±1.22 %, ECP I: 79±1.89 %) compared to control (MCP I: 63±1.20 %, 23±1.28 million/mL, 32±1.24 %, ECP I: 60±2.12 %, 22±1.60 million/mL, 35±2.64 %, respectively). [45]

The methanol subfraction (MSF) of C. papaya seeds (50 mg/kg bw) administered orally to three months old male Wistar albino rats (180-200g) each day for 360 days showed a total inhibition of sperm motility and significant (p < 0.05) decline in sperm density (day 120: 13.17±0.23 million/mL, day 180: 12.28±0.16 million/mL), and significantly (p < 0.01) decreased sperm viability (day 60: 36.19±1.66 %, day 120: 40.17±1.81 %) and increased numbers of sperm abnormalities (day 60: 47.07±4.41 %, day 120: 47.07±4.41 %, day 180: 51.08±5.92 %) compared to control (21.43±3.63 million/mL, 60.08±5.81 %, 36.14±6.11 %, respectively). The normal serum testosterone levels and 100% sterility were evident after 60 days of treatment. [46]

Wound healing activity

BioRex gel of fermented papaya preparation (FPP) administered to burn-induced male Wistar rats (400-450 g) for duration of 12 days showed accelerated wound healing by significantly (p < 0.05) reduced 2 fold lower of wound area compared to control rats (2092±196 mm2 and 884±531 mm2, respectively) and reduced the severity of local inflammation in rats with burn wounds. This effect is believed to be related to an increase in the effectiveness of intracellular bacterial killing by tissue phagocytes due to the inhibition of bacterial catalase, and antioxidant activity, which decreases the risk of oxidative damage to tissues. [47]

Aqueous extract of C. papaya leaves (50 and 100 mg/g Vaseline) was applied topically twice a day on dorsal neck excision wound of male Sprague Dawley rats (180-200 g). The extract showed significant (p < 0.05) decreased of healing time (50 mg/g Vaseline: 12.83±0.31 days, 100 mg/g Vaseline: 12.33±0.42 days) compared to Vaseline-treated control group (17.33±0.67 days). [48]

Antibacterial activity

Ethanol extract of C. papaya leaves (100 g/100 ml) showed inhibited growth of Escherichia coli (inhibition zone = 8.30 mm), Micrococcus luteus (8.23 mm), Pseudomonas aeruginosa (8.23 mm), Bacillus cereus (9.20 mm), Klebsiella pneumonia (6.17 mm) and Staphylococcus aureus (8.20 mm) compared to ciprofloxacin (E. coli = 23.50 mm, M. luteus = 16.97 mm, P. aeruginosa = 25.0 mm, B. cereus = 21.83 mm, K. pneumonia = 14.83 mm and S. aureus = 29.83 mm) using well diffusion method. [49]

C. papaya seed extracts showed antibacterial activity when tested against gram-positive and gram-negative organisms with most inhibition zone produced by B. cereus followed by E. coli, Streptococcus faecalis, S. aureus, Proteus vulgaris and Shigella flexneri. [50]

Petroleum ether, 1 % HCl, acetone, ethanol, and aqueous extract of C. papaya leaves showed antimicrobial activity towards S. aureus, E. coli, and P. aeruginosa. Petroleum ether extract significantly (p < 0.05) showed strongest and more powerful antibiotic (MIC: 2.0 mg/mL) compared to standard antibiotic drugs perflacin (MIC: 4.0 mg/mL) and cefuroxime (MIC: 6.0 mg/mL) for all bacteria. 1 % HCl extracts also showed significant (p < 0.05) antibiotic potential with MIC value of 9.6 mg/mL for S. aureus and E.coli, while MIC of 15.0 mg/mL for P. aeruginosa. Ethanol extract showed antibiotic property for all bacteria (MIC: 28.0 mg/mL), aqueous extract only for S. aureus and E.coli (MIC: 30 mg/mL), and acetone extract for all bacteria with different value (MIC: 24.0 mg/mL for S. aureus, 30.0 mg/mL for E.coli and P. aeruginosa). [51]

Antifungal activity

Ethanol extract of C. papaya leaves (100 g/100 ml) showed inhibited growth of Aspergillus niger (inhibition zone = 7.07 mm), Aspergillus flavus (6.20 mm), Candida albicans (8.23 mm), Candida tropicalis (10.0 mm), Cryptococcus neoformans (7.0 mm) and Candida kefyr (6.0 mm) compared to ketoconazole (A. niger = 7.40 mm, A. flavus = 8.23 mm, C. albicans = 8.83 mm, C. tropicalis = 10.10 mm, C. neoformans = 13.17 mm and C. kefyr = 11.17 mm) using well diffusion method. [49]

Antimalarial activity

Methanol (70%) extract of C. papaya leaves (200 mg/kg) was administered to adult Swiss albino mice (20 g) for duration of five days after 72 hours malaria-induction using Plasmodium berghei. The extract showed a significant (p < 0.05) reduction in parasitemia level from Day-1 (66%) to Day-5 of treatment (12%) compared to untreated control (Day-1: 66%, Day-5: 80%). The extract also significantly (p < 0.05) increased the percentage of chemo suppression (0.78±0.04% – 82.22±2.51%) compared to artesunate (3.43±0.21% – 96.60±2.77%) and Alstonia broonai (1.25±0.09% – 53.73±2.13%). [52]

Antiplasmodial activity

Ethanol extract of C. papaya leaves (25, 50, 100 and 150 µg/mL) showed antiplasmodial activity against chloroquine (CQ) - sensitive strain of Plasmodium falciparum with inhibition concentration at 50% of growth (IC50) of 40.8% at 25 µg/mL, 36.5% at 50 µg/mL, 25.3% at 100 µg/mL and 18.0% at 150 µg/mL compared to control group (1.0%). The extract also inhibited the growth of CQ - resistant strain of P. falciparum with IC50 of 50.2% at 25 µg/mL, 32.5% at 50 µg/mL, 21.4% at 100 µg/mL and 23.1% at 150 µg/mL compared to control (5.0 %) using in-vitro antiplasmodial assay. [53]

Carpaine isolated from methanol extract of C. papaya leaves (10 mg/kg BW) showed antiplasmodial activity when tested against P. falciparum with inhibition concentration at 50% of growth (IC50) of 0.21 µM and a selectivity index of 107, comparable to control drug chloroquine. [14]

Anti-insecticidal activity

Ethanol extract of C. papaya leaves (2, 4, 6, 8 and 10%) showed anti-insecticidal activity against the 1st to 4th instars larvae and pupae of Anopheles stephensi with lethal concentration at 50% growth (LC50) of 3.65, 4.28, 5.41, 6.70 and 7.50% respectively using larval/pupae toxicity test. [53]

A mixture of cotyledon (27 µg/mL) and tegument (17 µg/mL) of aqueous extract of C. papaya seeds (1:10, w/v) significantly (p < 0.001) caused 100% larval mortality against 3rd to 4th instars larvae of Aedes aegypti and LD50 was determined at 1.13 mg/mL using the dry seed weight (w/v). [54]

Platlet incresing activity

Aqueous extract of C. papaya leaves (400 and 800 mg/kg) was administered to cyclophosphamide-induced thrombocytopenic Wistar rats (100-125 g) for a duration of 15 days. The extract significantly (p < 0.001) increased the platelet count (400 mg/kg: 556833±30414 cells/mm3, 800 mg/kg: 831000±16118 cells/mm3) compared to cyclophosphamide- treated control group (164500±13304 cells/mm3). [55]

Anthelmintic activity

Cysteine proteinases in the crude extract of C. papaya latex (25 µM) showed in vitro anthelmintic activity by rapidly declined the motility of adult Protospirura muricola worm when incubated with the extract at 37oC for duration of 2 hours. In vivo experiment of the crude extract of C. papaya latex (0.2 ml) preceded with cimetidine administered orally to P. muricola-infected male BKW mice for duration of 7 days of post-worm-infection showed a significant reduction in female worm burden. [56]

Toxicity

Acute toxicity

Methanolic extract of C. papaya leaf (50 µg/mL) showed no toxicity towards HepG2 cell growth using crystal violet assay method. [37]

Oral single dose acute toxicity study on female Sprague Dawley rats (aged between 6 to 7 weeks old) using freeze dried C. papaya leaves aqueous extract on the parameters observed which includes physical observation, mortality, hematological, biochemical analysis, body weight, food and water intakes. All rats were observed for 14 days prior to necropsy. No death was found throughout the study period. Necropsy revealed no significant abnormality. LD50 > 2000 mg/kg. [57]

Sub-acute toxicity

Oral single dose acute toxicity study on male and female Sprague Dawley rats (aged between 6 to 7 weeks old) using freeze dried C. papaya leaves aqueous extract on the parameters observed which includes physical observation, mortality, hematological, biochemical analysis, body weight, food and water intakes and histopathology. All rats were observed for 13 weeks prior to necropsy. No death was found throughout the study period. Necropsy revealed no significant abnormality. However, significant (p < 0.05) differences was observed for biochemistry values (LDH, creatinine, total protein and albumin) which require further hepatotoxicity study. LD50 > 2000 mg/kg. [58]

Clinical Data

Clinical findings

Reported clinical trials:

Dengue Fever

An investigation to study the effect of C. papaya leave extracts as compared to broad spectrum antibiotics and antimalarial drugs for five days was carried out. This involved a 45-year old male patient diagnosed with Dengue fever with symptoms of body ache, breathing problem, shivering, vomiting and hypertension. The patient was administered with grinded C. papaya leaves mixed with some sucrose administered orally (25 mL) twice daily (morning and evening) for five consecutive days. The observations were made on the patient’s platelet count every 24 hours before and after the extract administration. Results showed recovery of platelet counts, white blood cells and neutrophils to its normal levels. Thus, C. papaya leaves extract exhibited potential activity against Dengue fever [59].

A pilot study on the beneficial effects of C. papaya leaf extract in combination with antiemetics, paracetamol and antibiotics on 12 patients (adult and children below 10 years old) with strong clinical suspicion of Dengue fever, who suffered for more than 3 days fever, more than 5 years of age, and platelet count of above 130000 per cu.mm. The patients was administered orally with C. papaya leaf extract crushed into juice form at 8-hour interval for adults (two 5mL doses) and children (two 2.5 mL doses) for nine consecutive days. The observations were made by taking blood sample every 24 hours to determine platelet count and other parameters. Results showed that platelet counts and total white cells increased within 24 hours of C. papaya leaf extract administration [60].

A randomized controlled trial involving 80 subjects was conducted to study the effects of C. papaya leaves extract capsules (CPC) to Dengue fever patient. The intervention group was given additional two CPC three times daily while the control group received standard treatment. Examination of blood was done twice daily (morning and afternoon) and the platelet count and hematocrit levels were determined. The result showed that CPC had significantly (p<0.05) increased the platelet count (6th examination: 133.88 ± 33.956) compared to control group (9th examination: 117.48 ± 24.550). In addition, no side effect was observed [61].

Antioxidant Defence System

C. papaya contains antioxidant phytochemicals, such as vitamin C, vitamin A and lycopene [62] [63]. In a small double-blind, placebo controlled study, a fermented extract of C. papaya (9 grams daily) was administered for 3 months followed by a 6-week washout period to 54 elderly patients without major diseases. The fermented papaya preparation (FPP) supplemented group showed a significant enhancement of the individual’s antioxidant defence system [64].

Papaya’s blood sugar regulatory properties are based, in part, on its antioxidant capacity. A fermented papaya preparation (FPP) was administered to 50 individuals with matching in age, 25 healthy (16 females and 9 males) and 25 with type-2 diabetes mellitus (13 females and 12 males) under treatment with oral antidiabetic drug, glybenclamide. Within two months, all subjects were given 3 grams of FPP daily, during lunch hour. FPP induced a significant decrease in plasma sugar levels in both healthy subjects and type 2 diabetic patients. Patients were able to reduce the dosage of their antidiabetic oral therapy. Thus, the FPP administration is suggested as an adjuvant drug to join the oral antidiabetic therapy in type 2 diabetes mellitus [66].

Burn Wound Infection

A clinical observation found that mashed C. papaya pulp applied daily to full thickness and infected burns appears to be effective in desloughing necrotic tissue, preventing burn wound infection, and providing a granulating wound suitable for the application of a split-thickness skin graft (STSG). Possible mechanisms of action include the activity of proteolytic enzymes chymopapain and papain, as well as an antimicrobial activity, although further studies are required [67].

Chemonucleosis

A specific purified fraction, chymopapain, is approved for chemonucleosis (the treatment of herniated intervertebral discs by injection). However, due to allergic and other adverse reactions, this extract of C. papaya enzymes is not routinely used medically. A study found that proteolytic enzymes found in C. papaya, decreased pain (up to 85%) after injection into the lumbar intervertebral disc of 80 patients suffering from intractable root pain due to herniated discs [68].

Potential Toxicity

Very few studies on potential toxicity have been described. A study was conducted to investigate the acute toxicity of C. papaya leaf extract on Sprague Dawley rats at a dose of 2000 mg/kg body weight (BW). No signs of toxicity and no deaths were observed. Based on the sighting study, a dose of 2000 mg/kg BW was selected and observed for 14 days. The study includes control and treatment group, each consisting of 5 female rats. The single oral dose of the C. papaya leaf extract did not produce mortality or significant changes in the body weight, food and water consumption. The relative weights of the internal organs were normal. However, haemoglobin (HGB), haematocrit (HCT), red blood cell (RBC) and total protein were significantly increase indicating dehydration. Apart from triglyceride, other biochemistry parameters demonstrated no significant changes as compared to the control [57].

In repeated dose 28-days oral toxicity study of C. papaya leaf extract in Sprague Dawley rats, the aim was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity by examining the general behavior, clinical signs, haematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds were tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups, while some biochemical parameters such as the total protein and HDL-cholesterol were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent [72].

Human Intestinal Parasitosis

In two randomized treatments, 60 asymptomatic Nigerian children with stool microscopic evidence of intestinal parasites received immediate doses (20 mL) of either an elixir composed with air-dried C. papaya seeds and honey (CPH) or honey alone (placebo) in order to determine the effectiveness of air-dried C. papaya seeds on human intestinal parasitosis. Repeat stool microscopic examinations were conducted 7 days postintervention for intestinal parasites. Significantly more subjects given CPH elixir than those given honey had their stools cleared of parasites. Results show air-dried C. papaya seeds are efficacious in treating human intestinal parasites and possess no harmful significant side effects. Their consumption offers a cheap, natural, harmless, readily available monotherapy and preventive strategy against intestinal parasitosis, especially in tropical communities [73].

Precautions

C. papaya is frequently used as a hair conditioner, but should be used in small amounts [26]. Discontinue if allergy occurs.

Cutting back on C. papaya consumption will resolve the discoloration of the skin because eating too much food that contains beta-carotene can cause a benign form of skin discoloration called carotenemia [26].

Side effects

Respiratory Distress

C. papaya flower pollen is able to induce respiratory IgE-mediated allergy. The existence of common allergens among C. papaya flower pollen, fruit and papain has been demonstrated by RAST inhibition [65].

Papain is also a potential allergen, according to Purdue University, people who eat too much C. papaya and ingest high levels of papain may develop symptoms consistent with hay fever or asthma, including wheezing, breathing difficulties and nasal congestion [26].

Excess/Overload Iron

Male with prostate dysfunction, such as Benign Prostatic Hyperplasia (BPH) or prostate cancer is suggested for not using C. papaya as a dietary intake or medicinal agent due to an increase in iron absorption. Excess iron may increase oxidative stress, especially in the aging male. Iron overload also may increase the risk of aggressively developing prostate cancer, and these associations might be modified by endogenous antioxidant capabilities [71].

Irritation/Allergic Reaction

C. papaya releases a latex fluid when not quite ripe or unripe, which can cause irritation and provoke allergic reaction in sensitive people. The latex concentration of unripe C. papaya is speculated to cause uterine contractions, which may lead to a miscarriage. C. papaya seed extracts in large doses have a contraceptive effect on rats and monkeys, but in small doses have no effect on the unborn animals [26].

Toxicity

Externally the C. papaya latex is an irritant to the skin and internally it causes severe gastritis. Some people are allergic to various parts of the fruit and even the enzyme papain has its negative properties [26].

Carotenemia

Excessive consumption of C. papaya with over a long period of time can cause carotenemia, the yellowing of soles and palms, which is otherwise harmless. However, a very large dose would need to be consumed; C. papaya contains about 6% of the level of beta-carotene found in carrots (the most common cause of carotenemia) [26].

Free Radical Scavenging Activity

C. papaya has many phenolic groups which may scavenge free radicals. Aqueous extract of C. papaya leaves shows anti-oxidant activity [26]. A study of the free radical scavenging activity of the fermented papaya preparation (FPP) by using an electron spin resonance (ESR) spectrometer shows that FPP scavenged 80% of hydroxyl radicals (OH) [80]. The oral administration of FPP would decrease the elevated of lipid peroxide levels in the ipsilateral and also increased the superoxide dismutase activity in the cortex and hippocampus of rats [80].

Gastrointestinal Symptoms

Papain that has the ability to calm the stomach can cause an upset stomach when taken in large amounts. The high fiber content of C. papaya can also contribute to disturbance of the digestive system. The latex of the fruit's skin can also cause irritation of the stomach [26].

Pregnancy/Breast Feeding

Not to be used by pregnant or nursing women without supervision of a healthcare professional. Normal consumption of ripe C. papaya (only in moderation) during pregnancy may not pose any significant danger [65] [79]. However, the unripe or semi-ripe C. papaya (which contains high concentration of the latex that produces marked uterine contractions) could be unsafe in pregnancy [79]. The C. papaya latex's main constituents are papain and chymopapain which have teratogenic (abnormalities of physiological development). C. papaya skins, seeds (dried or fresh), unripe fruit or latex may have abortifacient effects and may lead to a miscarriage [26] [79], while the toxicity can adversely affect the foetus [65] [69]. It does this by increasing the chances of uterine contractions as the papain acts like prostaglandin and oxytocin which are known to put a mother’s body into labour and hence, an adverse effect on the babies and mothers health. The latex can also cause marked oedema and haemorrhagic placentas which are bleeding and haemorrhaging from the edge of the placenta, this can result in severe complications in pregnancy and normally an early delivery [26]. The dosage seems to play a major role as young women taking too high a dosage over a long time can, according to reports, become infertile forever [79].

Age limitation

Two 5 mL doses at an 8 hour interval for adults and two 2.5 mL doses at an 8 hour interval for children <10 years [60].

Adverse reaction

Diuretic

When the aqueous root extract of C. papaya was given orally at a dose of 10 mg/kg to rats, a significant increase in urine output have been produced and showed similar profiles of urinary electrolyte excretion to that of Hydrochlorothiazide [65].

Abortifacient

A low dose aqueous crude extract of C. papaya seeds does not adversely affect prenatal development. However, a high dose of aqueous crude extract of C. papaya would have abortifacient side effect in which the toxicity can adversely affect the foetus [69].

Interaction & Depletion

Interaction with drug

Hepatoprotective

The ethanol and aqueous extracts of the fruit possess remarkable hepatoprotective activity against CCI4 induced hepatotoxicity. However hepatoprotective mechanism as well as active principles responsible for hepatoprotective activity of this plant is not yet known [65].

Ferum (iron)

Based on pharmacology, C. papaya may increase the absorption of iron. Use with caution if taking iron supplement or are predisposed to prostate problems [70] [71].

Aspirin or Warfarin

C. papaya extract exhibits a protective effect through free radical scavenging properties and reduces oxidative damage or gastric ulceration caused by aspirin [74]. However, based on pharmacology, papain should be used with caution in individuals with bleeding disorders or those who taking blood-thinning medications such as aspirin or warfarin (Coumadin). Discontinue if allergy occurs.

Metformin and Glimepiride

Leaf extract of C. papaya significantly delays the onset of hypoglycaemic activity of glimepiride, and increases the hypoglycaemic effect of metformin with the variables interacting differently for each drug-extract combinations [77].

Interaction with other Herbs

No documentation.

Contraindications

Skin Discoloration

Eating too much of a yellow, green or orange coloured food that contains beta-carotene (a potent antioxidant) can cause a benign form of skin discoloration called carotenemia. The palms of the hands and soles of the feet are the most visible areas of the body affected by carotenemia [26] [79]. C. papaya is rich in beta-carotene and this change of colouring may happen with a high-intake of C. papaya over a long period of time [79].

Case Report

Dengue Fever

A 23-year-old male, with a fever of 102°F for the preceding 2 days was administered a calculated dose for five days. Symptoms include nausea, red skin, severe body ache and weakness. He reported that he used to visit friends and poorly managed tea stores after sunset every evening after his swimming sessions. He was bitten by a mosquito somewhere. After 2 days he had high-grade fever with severe body ache, weakness and nausea. He was admitted and tested for typhoid, malaria and dengue. Dengue Rapid N51 antigen was found to be positive. The haematological reports also revealed an abrupt decline in the patient's thrombocyte counts. Blood samples were tested for complete blood count before and after the administration of C. papaya leave extract. Thrombocyte count had increased from 28000/micro liter to 138000/micro liter at the end of five days [78].

A case was reported in which a 45 years old man has bitten by carrier mosquitoes that caused Dengue fever, has increased in platelet, leucocyte, and neutrophil count after given 25 mL water extract of C. papaya twice daily for five consecutive days, compared with before treatment [59].

In Sri Lanka, a case report of C. papaya for Dengue fever patient showed increased in platelet and leucocyte count of 12 patients in 24 hours after administration of 5 mL C. papaya leaves extract twice daily [60].

Dosage

C. papaya and the enzyme papain have been reported safe in recommended doses [69]. Two 5 mL doses at an 8 hour interval for adults and two 2.5 mL doses at an 8 hour interval for children <10 years [60].

Dosage Range

For Ulcers: Peptic and Stomach

  1. C. papaya diet; C. papaya flower essence; skin extract; homeopathic C. papaya D3 (3 times) [79].
  2. 1-3 teaspoonfuls (5-10gm) of dried C. papaya leaves in a cup of hot water. Drink 2-3 times daily.

For Ulcers: External

The skin is applied with the pulp side down on the ulcer. Green C. papaya is more effective than ripened C. papaya [79].

Worms-All & Other Intestinal Parasites of the Intestines

In India, treatment with C. papaya, will take for three days in a row. 1 tablespoon latex, one tablespoon honey and 4 tablespoons hot water are mixed together and taken on an empty stomach. Meals may be taken after taking this mixture. Two hours later a mixture of 50 mL castor oil and 300 mL warm milk are taken [79].

Topically For Wounds

C. papaya latex formulated in the Carbopol (hydroalcoholic) gel is effective in the treatment of burns [76]. C. papaya fruit is mashed and applied daily to full thickness and infected burns. There are pharmaceutical products for topical wound application (isolated papain usually combined with urea) [67]. From a study of the effects of C. papaya latex on the healing of burn wounds in rats found that the C. papaya latex contained digestive enzymes which might clean burn wounds [75].

Antioxidant Defence

As the fermented C. papaya fruit is a promising nutraceutical as an antioxidant, it improves the antioxidant defence in elderly patients even without any overt antioxidant deficiency state at the dose of 6-9g/day orally [65].

Immune Support

If taking the fermented C. papaya extract for immune support, start with 6-9 grams a day for the first 2-3 days (such as at the beginning of symptoms of a cold) and then decrease to 3 grams daily for 2-3 weeks.

As Digestive Enzyme

  1. Fresh C. papaya juice: 1-3 teaspoonfuls (5-15 mL) of C. papaya juice three times daily after meals.
  2. Fresh C. papaya pulp: 1-2 tablespoonfuls (15-30gm) C. papaya fruit three times daily after meals.
  3. Papain: 10-50mg up to three times daily after meals.

Most Common Dosage

Information and data have not been established. There is no common dosage for C. papaya due to the variety of preparations in use.

Standardisation

No standardization known.

Poisonous Management

No documentation.

Line drawing

carica papaya

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