text:
IMEvidence
Medicinal Herbs & Plant Database
Malaysian Herbal Monograph
Medicinal Herbs & Plants Monographs
Policy, Law, Standard and IPR
Trade & Business
Traditional Complementary Medicine (T&CM)
ASEAN Task Force on Traditional Medicines
Home Medicinal Herbs & Plant Database Medicinal Herbs & Plants Monographs
Carica papaya L
Carica papaya L. [1]
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]
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]
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
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]
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 findings
Reported clinical trials:
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].
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].
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].
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].
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].
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].
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
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].
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].
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
C. papaya diet; C. papaya flower essence; skin extract; homeopathic C. papaya D3 (3 times) [79].
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].
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
Fresh C. papaya juice: 1-3 teaspoonfuls (5-15 mL) of C. papaya juice three times daily after meals.
Fresh C. papaya pulp: 1-2 tablespoonfuls (15-30gm) C. papaya fruit three times daily after meals.
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.
No standardization known.
Poisonous Management
The Plant List. Ver1.1. Carica papaya L. [updated 2012 Apr 18; cited 2015 Jan 21]. c2013. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2700919
Villegas VN. Carica papaya L. In: Verheij E W M, Coronel R E, editors. Plant resources of South-East Asia no. 2: Edible fruits and nuts. The Netherlands: Backhuys Publishers, 1991; p. 108-112
Philippines medicinal plants. Carica papaya L. [homepage on the internet] c2014. [updated 2014, cited 2015 Jan 21] Available from http://www.stuartxchange.org/Papaya.html
Compendium of Medicinal Plants Used in Malaysia. Vol. 1. Kuala Lumpur: HMRC-IMR: 2002. p.148.
Burkill IH. A dictionary of the economic products of the Malay Peninsula. Vol 1. (A-H). Great Britain; 1935. p. 459.
Fuentes G, Santamaria JM. Papaya (Carica papaya L.): Origin, domestication, and production. In: Ming R, Moore PH, editors. Genetics and genomics: Crops and models. USA: Springer Science & Business Media; 2013. p.3.
Paull RE, Duarte O. Crop production science in horticulture 20: Tropical fruits. Vol 1. 2nd ed. USA: CABI; 2010. p.292.
Pantoja A, Follet PA, Villanueva-limenez JA. Pest of Papaya. In: Pena JE, Sharp JL, Wysoki M, editors. Tropical fruit pests and pollinator: biology, economic importance, natural enemies and control. UK: CABI; 2002. p. 131.
Jimenez V M, Mora-Newcomer E, Gutierrez-Soto M V. Biology of the papaya plant. In: Ming R, Moore P H, editors. Genetics and genomics of papaya. New York: Springer Science & Business Media, 2014; p. 17-33
Storey W B. Theory of the derivations of the unisexual flowers of caricaceae. Agronomia Tropical. 1967; 17:273-321
Zunjar V, Mammen D, Trivedi BM. Antioxidant activities and phenolics profiling of different parts of Carica papaya by LCMS-MS. Natural product research. 2014:1-3.
Canini A, Alesiani D, D'Arcangelo G, Tagliatesta P. Gas chromatography–mass spectrometry analysis of phenolic compounds from Carica papaya L. leaf. Journal of Food Composition and Analysis. 2007;20(7):584-90.
Juárez-Rojop IE, Tovilla-Zárate CA, Aguilar-Domínguez DE, et al. Phytochemical screening and hypoglycemic activity of Carica papaya leaf in streptozotocin-induced diabetic rats. Revista Brasileira de Farmacognosia. 2014;24(3):341-7.
Julianti T, De Mieri M, Zimmermann S, et al. HPLC-based activity profiling for antiplasmodial compounds in the traditional Indonesian medicinal plant Carica papaya L. Journal of ethnopharmacology. 2014;155(1):426-34.
Singh O, Ali M. Phytochemical and antifungal profiles of the seeds of Carica papaya L. Indian journal of pharmaceutical sciences. 2011;73(4):447-51.
Gayosso-García Sancho LE, Yahia EM, González-Aguilar GA. Identification and quantification of phenols, carotenoids, and vitamin C from papaya (Carica papaya L., cv. Maradol) fruit determined by HPLC-DAD-MS/MS-ESI. Food Research International. 2011;44(5):1284-91.
Gouado I, Schweigert FJ, Ejoh RA, Tchouanguep MF, Camp JV. Systemic levels of carotenoids from mangoes and papaya consumed in three forms (juice, fresh and dry slice). European journal of clinical nutrition. 2007;61(10):1180-8.
Abdelkafi S, Abousalham A, Fendri I, et al. Identification of a new phospholipase D in Carica papaya latex. Gene. 2012;499(2):243-9.
Abdelkafi S, Ogata H, Barouh N, et al. Identification and biochemical characterization of a GDSL-motif carboxylester hydrolase from Carica papaya latex. Biochimica et biophysica acta. 2009;1791(11):1048-56.
Mueller MS, Mechler E. Medicinal Plants in Tropical Countries: Traditional Use, Experience, Facts. Stuttgart (Germay): Thieme; 2011.
Iwu Maurice M. Handbook of African Medicinal Plants: Second Edition. Danver. 2014. p.171.
Quattrocchi U. CRC World Dictionary of Medicinal and Poisonous Plants: Common Names, Scientific Names, Eponyms, Synonyms, and Etymology. Florida: CRC Press Taylor & Francis Group. 2012.
Ong HC, Ruzaila BN, Milow P. Traditional knowledge of medicinal plants among the Malay villagers in Kampung Tanjung Sabtu, Terengganu, Malaysia. Indian Journal of Traditional Knowledge. 2011;10(3):460-465.
Ong HC, Norzalina J. Malay herbal medicine in Gemencheh, Negri Sembilan, Malaysia. Fitoterapia. 1999;70:10-14.
Ong HC, Rosnaini MZ, Millow P. Traditional knowledge of medicinal platns among the Malay villagers in Kampung Mak Kemas, Terengganu, Malaysia. Ethno. Med. 2011;5(3):175-185.
Aravind G, Debjit B, Harish G. Traditional and medicinal uses of Carica papaya. Journal of Medicinal Plants Studies. 2013;1(1):7-15.
Novy JW. Medicinal Plants of the Eastern Region of Madagascar. J Ethnopharmacol. 1997;55(2):119-126.
Khare CP. Indian Herbal Remedies: Rational Western Therapy, Ayurvedic, and Other Traditional Usage, Botany. New Delhi: Springer. 2004. p. 128-129
Food and Agriculture Oragnization (FAO) Food and Nutrition Paper. Traditional Food Plants. Rome: FAO of the United Nations. 1988. p. 136.
Mueller MS, Mechler E. Medicinal Plants in Tropical Countries: Traditional Use, Experience, Fact. Stuttgart: Thieme. 2005.
Hamzah RU, Jigam AA, Makun HA, Egwim EC. Antioxidant Properties of Selected African Vegetables, Fruits and Mushrooms: A Review (Chapter 9). In: Makun HA, editors. Mycotoxin and Food Safety in Developing Countries. Croatia: InTech Open; 2013. p. 221-222.
Isela EJ-R, Juan CD-Z, Jorge LB-C, et al. Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats. Biomedcentral Complementary and Alternative Medicine. 2012;12:236.
Yasmin M, Prabhu B. Antihyperglycemic and hypolipidemic activities of aqueous extract of Carica papaya Linn. leaves in alloxan-induced diabetic rats. Journal of Ayurveda and Integrated Medicine. 2012;3(2):70 -74.
Tan S-A, Ramos S, Martin MA, et al. Protective effects of papaya extracts on tert-butyl hydroperoxide mediated oxidative injury to human liver cells (An in-vitro study). Free Radicals and Antioxidants. 2012;2(3):10-9.
Indran M, Mahmood AA, Kuppusamy UR. Protective effect of Carica papaya L. leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats. West Indian Med Journal. 2008;57(4):323.
Okoko T, Ere D. Reduction of hydrogen peroxide-induced erythrocyte damage by Carica papaya leaf extract. Asian Pacific Journal of Tropical Biomedicine. 2012: 449-453.
Tan S-A, Goya L, Ramanathan S, Sulaiman SF, Alam M, Navaratnam V. Chemopreventive effects of standardized papaya leaf fraction on oxidatively stress human liver cells. Food Research International. 2014; 64: 387-395.
Zhang J, Mori A, Chen Q, Zhao B. Fermented papaya preparation attenuates beta-amyloid precursor protein: beta-amyloid-mediated copper neurotoxicity in beta-amyloid precursor protein and beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells. Neuroscience. 2006;143(1):63-72.
Tham CS, Chakravarthi S, Haleagrahara N, Alwis RD. Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract. Experimental and therapeutic medicine. 2013;5(2):648-52.
Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. Journal of Ethnopharmacology. 2010;127(3):760-7.
Kalil IC, Gibson BAV, Ribeiro CA, et al. Antimutagenic activity of Carica papaya L. assayed in vivo by micronucleus test. Journal of Basic and Applied Pharmaceutical Sciences. 2011;32(3):419-423.
Imaga NOA, Gbenle GO, Okochi VI, et al. Antisickling property of Carica papaya leaf extract. African Journal of Biochemistry Research. 2009;3(4): 102-106.
Mojica-Henshaw MP, Francisco AD, De Guzman F, Tigno XT. Possible immunomodulatory actions of Carica papaya seed extract. Clin Hemorheol Microcirc. 2003;29(3-4):219-229.
Hasimun P, Suwendar, Ernasari GI. Analgetic activity of papaya (Carica papaya L.) leaves Extract. Procedia Chemistry. 2014;13:147-9.
Lohiya NK, Mishra PK, Pathak N, et al. Efficacy trial on the purified compounds of the seeds of Carica papaya for male contraception in albino rat. Reproductive Toxicology. 2005;20(1): 135-148.
Manivannan B, Mittal R, Goyal S, Ansari AS, Lohiya NK. Sperm characteristics and ultrastructure of testes of rats after long-term treatment with the methanol subfraction of Carica papaya seeds.Asian J Androl. Sep2009;11(5):583-599.
Mikhal'chik EV, Ivanova AV, Anurov MV, et al. Wound-healing effect of papaya-based preparation in experimental thermal trauma. Bull Exp Biol Med. 2004;137(6):560-562.
Mahmood AA, Sidik K, Salmah I. Wound healing activity of Carica papaya L. aqueous leaf extract in rats. International Journal of Molecular Medicine and Advance Sciences. 2005;1(4):398-401.
Baskaran C, Bai VR, Velu S, Kumaran K. The efficacy of Carica papaya leaf extract on some bacterial and a fungal strain by well diffusion method. Asian Pacific Journal of Tropical Disease. 2012;2:S658-S62.
Dawkins G, Hewitt H, Wint Y, Obiefuna PC, Wint B. Antibacterial effects of Carica papaya fruit on common wound organisms. West Indian Med J. 2003;52(4):290-292.
Orhue PO, Momoh ARM. Antibacterial activities of different solvent extracts of Carica papaya fruit parts on some gram positive and gram negative organisms. International Journal of Herbs and Pharmacological Research. 2013;2(4):42-7.
Arise RO, Malomo SO, Lawal MM. Comparative antimalarial and toxicological effects of artemisinin with methanolic extract of Carica papaya leaves and bark of Alstoniabroonai in animal models. Advances in Natural and Applied Sciences. 2012;6(2):116-23.
Kovendan K, Murugan K, Panneerselvam C, et al. Antimalarial activity of Carica papaya (Family: Caricaceae) leaf extract against Plasmodium falciparum. Asian Pacific Journal of Tropical Disease. 2012;2:S306-S11.
Nunes NN, Santana LA, Sampaio MU, Lemos FJ, Oliva ML. The component of Carica papaya seed toxic to A. aegypti and the identification of tegupain, the enzyme that generates it. Chemosphere. 2013;92(4):413-20.
Patil S, Shetty S, Bhide R, Narayanan S. Evaluation of platelet augmentation activity of Carica papaya leaf aqueous extract in rats. Journal of Pharmacognosy and Phytochemistry. 2013;1(5):57-60.
Stepek G, Buttle DJ, Duce IR, Lowe A, Behnke JM. Assessment of the anthelmintic effect of natural plant cysteine proteinases against the gastrointestinal nematode, Heligmosomoides polygyrus, in vitro. Parasitology. 2005;130(2):203-211.
Halim SZ, Abdullah NR, Afzan A, Abdul Rashid A, Jantan I and Ismail Z. Acute toxicity study of Carica papaya leaf extract in Sprague Dawley rats. Journal of Medicinal Plants Research. 2011; 5:1867-1872
Ismail Z, Halim SZ, Abdullah NR, Afzan A, Abdul Rashid BA and Jantan I. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A subchronic toxicity study in Sprague Dawley rats. Evidence-Based Complementary and Alternative Medicine. 2014: 1-10
Ahmad N, Fazal H, Ayaz M, Abbasi BH, Mohammad I, Fazal L. Dengue fever treatment with Carica papaya leaves extracts. Asian Pacific Journal of Tropical Biomedicine. 2011; 1(4): 330-333.
Hettige S. Salutary effects of Carica papaya leaf extract in dengue fever patients – a pilot study. Sri Lankan Family Physician. 2008; 29: 17-19.
Yunita F, Hanani E, Kristianto J. The effect of Carica papaya L. leaves extract capsules on platelets count and hematocrit level in dengue fever patient. International Journal of Medicinal and Aromatic Plants. 2012; 2(4): 573-578.
Aruoma OI, Colognato R, Fontana I, et al. Molecular effects of fermented papaya preparation on oxidative damage, MAP Kinase activation and modulation of the benzo[a]pyrene mediated genotoxicity. Biofactors. 2006; 26(2): 147-159.
Amer J, Goldfarb A, Rachmilewitz EA, Fibach E. Fermented papaya preparation as redox regulator in blood cells of beta-thalassemic mice and patients. Phytotherapy Research. Jun 2008; 22(6): 820-828.
Marotta F, Weksler M, Naito Y, Yoshida C, Yoshioka M, Marandola P. Nutraceutical supplementation: effect of a fermented papaya preparation on redox status and DNA damage in healthy elderly individuals and relationship with GSTM1 genotype: a randomized, placebo-controlled, cross-over study. Annals of the New York Academy of Sciences. 2006; 1067: 400-407.
Krishna KL, Paridhavi M, Patel JA. Review on nutritional, medicinal and pharmacological properties of papaya (Carica papaya Linn.). Natural Product Radiance. 2008; 7(4): 364-373.
Danese C, Esposite D, D'Alfonso V, Cirene M, Ambrosino M, Colotto M. Plasma glucose level decreases as collateral effect of fermented papaya preparation use. La Clinica Terapeutica. 2006; 157(3): 195-198.
Starley IF, Mohammed P, Schneider G, Bickler SW. The treatment of paediatric burns using topical papaya. Burns. 1999; 25(7):636-639.
Troisier O, Gozlan E, Durey A, Rodineau J, Gounot-Halbout MC, Pelleray B. [The treatment of lumbosciatica by intra-discal injection of proteolytic enzymes (nucleolysis). 80 cases (author's transl)]. La Nouvelle Presse Médicale. 1980; 9(4): 227-230.
Oderinde O, Noronha C, Oremosu A, Kusemiju T, Okanlawon OA. Abortifacient properties of aqueous extract of Carica papaya (Linn) seeds on female Sprague-Dawley rats. Nigerian Postgraduate Medical Journal. 2002;9(2):95-98.
Ballot D, Baynes RD, Bothwell TH, et al. The effects of fruit juices and fruits on the absorption of iron from a rice meal. British Journal of Nutrition. 1987; 57(3): 331-343.
Choi JY, Neuhouser ML, Barnett MJ, et al. Iron intake, oxidative stress-related genes (MnSOD and MPO) and prostate cancer risk in CARET cohort. Carcinogenesis. 2008; 29(5): 964-970.
Afzan A, Abdullah NR, Halim SZ, et al. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats. Molecules. 2012;17(4): 4326-4342.
Okeniyi JA, Ogunlesi TA, Oyelami OA, Adeyemi LA. Effectiveness of dried Carica papaya seeds against human intestinal parasitosis: a pilot study. Journal of Medicinal Food. 2007; 10(1): 194-196.
Ologundudu A, Lawal AO, Ololade IA, Omonkhua AA, Obi FO. The antiulcerogenic activity of aqueous extract of Carica papaya fruits on aspirin induced ulcer in rats. International Journal of Toxicology. 2008; 5(2).
Shuid AN, Anwar MS, Yusof AA. The effects of Carica papaya Linn. latex on the healing of burn wounds in rats. Jurnal Sains Kesihatan Malaysia. 2005; 3(2): 39-47.
Gurung S, Škalko-Basnet N. Wound healing properties of Carica papaya latex: In vivo evaluation in mice burn model. Journal of Ethnopharmacology. 2009; 121(2): 338-341.
Fakeye TO, Oladipupo T, Showande O, Ogunremi Y. Effects of coadministration of extract of Carica papaya Linn (family Cariaceae) on activity of two oral hypoglycemic agents. Tropical Journal of Pharmaceutical Research. 2007; 6(1): 671-678.
Siddique O, Sundus A, Ibrahim MF. Effects of papaya leaves on thrombocyte counts in dengue-a case report. JPMA. The Journal of the Pakistan Medical Association. 2014; 64(3): 364-366.
Tietze HW. Papaya the medicine tree. Third edition. Bermagui, Australia: Harald W. Tietze Publishing PL: 2003; p. 116.
Imao K, Wang H, Komatsu M, Hiramatsu M. Free radical scavenging activity of fermented papaya preparation and its effect on lipid peroxide level and superoxide dismutase activity in iron‐induced epileptic foci of rats. IUBMB Life. 1998; 45(1): 11-23.
Copyright 2010-2018, All Rights Reserved - Global Information Hub On Integrated Medicine (Globinmed)


text:
Sensor Product News, Tips, and learning resources for the Design Engineering Professional.
Sensor-specific software
Vision software
Creating cryogenic environments for electronics
November 4, 2020 By Jeff Shepard
This FAQ series has gone to extremes and looked at "electronics that operate in extreme heat" (up to 800°C) and "electronics that operate in extreme cold" at cryogenic temperatures. This third and final FAQ will consider the various methods available to create artificial cryogenic environments.
The temperature where refrigerated temperatures end and cryogenic temperatures begin is not universally defined. The U.S. National Institute of Standards and Technology considers cryogenic temperatures to be below −180°C (93K; −292°F). That temperature was selected because the normal boiling points of gases such as helium, hydrogen, neon, nitrogen, oxygen, and normal air, lie below −180°C. Simultaneously, Freon, hydrocarbons, and other common refrigerants have boiling points above −180°C.
In addition, there is often a distinction made between high-temperature cryogenics and low-temperature cryogenics. Liquid nitrogen with a boiling point of 77.09K is considered "high-temperature cryogenics" (as in "high-temperature superconductivity"). The use of liquid helium with a boiling point of 4.214K (3.19K for helium-3) is considered low-temperature cryogenics. It is often associated with noise-sensitive uses such as quantum computers, superconducting quantum interference devices (SQUIDs), nuclear magnetic resonance spectroscopy, magnetic resonance imaging, microwave preamplification, and so on.
Direct liquid cooling
There are several ways to produce a cryogenic environment; direct liquid cooling, the use of a cryocooler or cryogenic refrigerator, and various techniques that directly manipulate individual atoms to effect cooling. Liquefied gases, such as liquid nitrogen and liquid helium, are used directly in many cryogenic applications. Liquid nitrogen is the most commonly used and least expensive element used in cryogenics. Liquid helium is also commonly used. It is more expensive and difficult to handle than liquid nitrogen but allows for the lowest attainable temperatures to be reached.
This 320kVDC, 3.2GW, high-temperature superconductor cable system uses liquid nitrogen and carries currents up to 10kA over long distances with minimal resistive losses. (Image: Nexans)
For example, liquid nitrogen is used in superconducting power cables, for CCD cameras in astronomy, and to maintain a low temperature around the primary liquid helium cooling system of high-field superconducting magnets used in nuclear magnetic resonance spectrometers and magnetic resonance imaging systems.
These liquids may be stored in Dewar flasks, which are double-walled containers with a high vacuum between the walls to reduce heat transfer into the liquid. Typical laboratory Dewar flasks are spherical, made of glass, and protected in a metal outer container. Dewar flasks for extremely cold liquids such as liquid helium are inside another double-walled container filled with liquid nitrogen.
Cryocoolers and cryogenic refrigerators
A cryocooler is a specialized refrigerator designed to reach cryogenic temperatures. Cryocoolers tend to be smaller systems, typically up to about 20kW, but can be as small as 2W. Typical applications for cryocoolers include high-temperature superconductivity (HTS) filters, high altitude balloons, refrigeration, germanium detectors, IR detectors, radio telescopes, laser diode cooling, and general research, among others. Large systems, for example, MW-sized systems used to cool the superconducting magnets in particle accelerators, are generally referred to as cryogenic refrigerators.
This cryocooler handles a nominal heat load of 16W at 77K with a temperature stability of 0.1K (Image: Sunpower)
Cryocoolers use a cryogenic fluid as the working substance and employ moving parts to cycle the fluid around a thermodynamic cycle. The fluid is typically compressed at room temperature (300K), precooled in a heat exchanger, then expanded at some low temperature. The returning low-pressure fluid passes through the heat exchanger to precool the high-pressure fluid before entering the compressor intake. The cycle is then repeated. There are several physical embodiments of cryocoolers, but the general theory of operation is the same. Usually, helium is the working fluid, which can produce a temperature of about 4.2K, reducing almost 100:1 versus room temperature.
Laser, evaporative, RF, and magnetic cooling
Laser cooling includes a number of techniques in which atomic and molecular samples are cooled down to near absolute zero. Laser cooling techniques rely on the fact that when an atom absorbs and re-emits a photon of light, its momentum changes. The first example of laser cooling and still the most common method (so much so that it is still often referred to simply as 'laser cooling') is Doppler cooling. Doppler cooling involves light with frequency tuned slightly below an electronic transition in an atom. Because the light is detuned to the "red" (i.e., at a lower frequency) of the transition, the atoms will absorb more photons if they move towards the light source due to the Doppler effect. An atom moving towards the laser sees it blue-shifted and absorbs the photon, slowing the atom. Slowing atoms reduces the temperature.
Evaporative cooling is an atomic physics technique to achieve high phase-space densities, which typically cannot reach optical cooling techniques. Atoms trapped in optical or magnetic traps are cooled as the trap depth is decreased, and the hottest atoms (with the highest kinetic energy) leave the trap. The hot atoms leaving the trap are on the tail of the Maxwell-Boltzmann distribution (which defines the particle speeds, and thereby the particle energies, in gas). Therefore, they carry away a significant amount of kinetic energy, mitigating the loss of atoms by an overall increase in phase space density.
Often RF energy is used to drive the hottest atoms from the trap. The RF radiation is commonly referred to as an RF knife because it cuts the hottest atoms out of the trap.
Magnetic refrigeration is a cooling technology based on the magnetocaloric effect. This technique can be used to attain extremely low temperatures and the ranges used in common refrigerators. The first working magnetic refrigerators were constructed by several groups beginning in 1933. Magnetic refrigeration was the first method developed for cooling below about 0.3K.
The magnetocaloric effect is a magneto-thermodynamic phenomenon in which a temperature change of a suitable material is caused by exposing the material to a changing magnetic field. Low-temperature physicists also know this as adiabatic demagnetization. In that part of the refrigeration process, a decrease in the strength of an externally applied magnetic field allows the magnetic domains of a magnetocaloric material to become disoriented from the magnetic field by the agitating action of the thermal energy (phonons) present in the material.
If the material is isolated so that no energy is allowed to (re)migrate into the material during this time (i.e., an adiabatic process), the temperature drops as the domains absorb the thermal energy to perform their reorientation. The randomization of the domains occurs in a similar fashion to the randomization at the curie temperature of a ferromagnetic material, except that magnetic dipoles overcome a decreasing external magnetic field. At the same time, energy remains constant, instead of magnetic domains being disrupted from internal ferromagnetism as energy is added.
In this magnetic cooling diagram, a Gadolinium alloy heats up inside the magnetic field. It loses thermal energy to the environment as it exits the field and becomes cooler than when it entered. (Image: Wikipedia)
One of the most notable examples of the magnetocaloric effect is in the chemical element gadolinium and some of its alloys. Gadolinium's temperature increases when it enters certain magnetic fields. When it leaves the magnetic field, the temperature drops. The effect is considerably stronger for the gadolinium alloy Praseodymium alloyed with nickel. It has such a strong magnetocaloric effect that it has allowed scientists to approach within one millikelvin, one-thousandth of a degree above absolute zero.
As shown, electronics is a versatile technology and can be designed for a wide range of environments. This FAQ series has gone to extremes and has looked at developments in electronic systems from +800°C in part one down to nearly absolute zero in part two.
Cryocooler, Wikipedia
Cryogenics, Wikipedia
Magnetic refrigeration, Wikipedia
Nexans completes successful qualification testing of 'Best Paths' superconductor cable for HVDC power links, Nexans
Electronics that operate in cryogenic cold
Electronics that operate in extreme heat to 800°C
LVDT position sensor, Part 2: Characteristics
What are cryogenic temperature measurements? Part 2
Thermocouples Take the Heat
Filed Under: Development Tools, Featured, Frequently Asked Question (FAQ), Temperature Tagged With: FAQ
Randy Frank delivers weekly sensor industry news, sensor resources, new sensor product innovations and more.
Implementing Position Sensors for Hazardous Areas & Safety
How New Rotary Sensor Technology Enables New Application Solutions
Magnetic sensor ensures safety features in depaneling machines
Tweets by SensorTips

redpajama_set_name: RedPajamaCommonCrawl


Seasoned hunters looking to expand their kitchen repertoire will certainly be pointed in the right direction with this comprehensive guide.
For the true gourmet, nothing beats the freshest cuts of meat, especially when it is free-range and naturally fed. But this can also be a prohibitively expensive way to eat. The alternative to store-bought meats is, of course, hunting. Hunters have access to what is essentially the freshest and healthiest meat, poultry, and fish available; they just have to get it themselves. Wild Gourmet merges the worlds of hunting and culinary excellence in a thorough and beautifully illustrated book. Compiled by the Boone and Crocket Club (a hunting club formed by Teddy Roosevelt), it is an excellent source of otherwise difficult-to-find information.
The chefs involved in Wild Gourmet present not only dishes inspired by a wide variety of culinary traditions (including Mexican, Indian, Japanese, Italian, and others) but also an intriguing assortment of meat. Everything from salmon to squirrel turns up here. A substantial portion of the book is dedicated to processing the meat. Since the average American cook knows little of this beyond skinning the occasional chicken or deveining shrimp, this section is highly informative. Processing is meticulously documented, so much so that the less dedicated chef may find the photographs a bit disturbing. Hunters, on the other hand, are not generally a squeamish bunch, and it is hunters, after all, for whom the book is written.
Most of the recipes involve straightforward, uncomplicated, and clearly explained techniques. Wild Gourmet may become daunting for most home cooks insofar as the equipment needed to process venison, elk, or other large game, in addition to the storage space required once the game is processed. The same goes for smoking or cooking on a spit. But for a hunter and chef with an outfitted cabin out in the country, this is all quite feasible.
Wild Gourmet is a colorful, visually appealing hardcover volume with an elegant cover. Given the popularity of Paleo diets and the farm-to-table movement, this book provides a wealth of information for those wanting to go one step further.


With its cosiness the Anantara Veli Maldives will offer you one of the best and most outstanding stays you ever experienced. For online reservation please use booking form and experience the hotel's unique cosiness.
Located within the South Malé Atoll, Anantara Veli Maldives offers over water bungalows. It features a water sports and diving centre and 5 dining options with views of the ocean. Anantara Veli Maldives features accommodation surrounded by blue waters and white sands. Each room comes with 24-hour room service and has a flat-screen TV, DVD player and an espresso machine. Guests can enjoy a workout at the fully equipped fitness centre or swim in the infinity edge pool. Massage, facial and body treatments are offered at the Anantara Spa. A breakfast buffet and fresh seafood is served at the 73 Degrees Restaurant. Other food options include Thai and Japanese cuisines. Drinks are available at the poolside bar, Dhoni. Anantara Veli Maldives is a 30-minute speed boat ride away from Malé International Airport. Boat transfers are provided for a fee.
Guests must advise return flight details at the time of making their reservations, at least 72 hours prior to their arrival. The resort will be arranging roundtrip speedboat transfers (available anytime of the day) at an additional cost to be paid directly by guest to the hotel.


Pentax 645Z will use Sony's 100 MP Medium Format sensor?
Pentax K80 is expected to be announced in Q2, 2018?
Can we expect Mega Zoom camera from Canon in 2018?
Tamron 24-70mm f/2.8 VC G2 - Still waiting to be announced?
Is Canon 1400D/T7 coming in 2017?
Canon SX70 HS coming in September, 2016?
Canon SX70 HS, when will it announce?


text:
SouthworldNews June 2012Madagascar – Worrying signs
Thursday, 24 May 2012 9:49
Written by:	Fr.Carmine
Category:	News June 2012
Africa, Madagascar
Madagascar is on edge. Some insiders predict that the unity government headed by the prime minister Jean Omer Beriziky could collapse soon. It could also be the case of all other transitional institutions. Further complex issues have emerged while the solution to the political crisis is moving at slow pace. Observers express concern about the situation prevailing in Madagascar.
Not a week passes by without annoying events occurring. The most bizarre one is the linking of Sylvain Manoriky – acting minister for fishing and marine resources – to sorcery against interim president Andry Rajoelina. The claim comes from the DTS, a police unit under direct control of the presidency. The peculiar event made headlines early in May. The episode resulted in much ado, and was widely condemned, even by the unity government.
The agreements for transition call for fresh elections this year, but the government seems unable to address the issue. Talking to Ban Ki-moon at the UN headquarters in New York early in May, Malagasy leaders spoke of their special focus on polls preparations and asked for more UN support. Yet, the recently formed Malagasy electoral commission is slow in communicating its agenda. The timid approach to the issue of elections pushed supporters of ousted president Marc Ravalomanana – in exile in South Africa since 2009 – to suspend participation in the transitional institutions.
Ministers faithful to Ravalomanana have not showed up for the weekly Cabinet meetings and the Ministers Councils since mid April. Accordingly, parliamentarians loyal to the former president refuse to take part in the current parliamentary session. Beriziky tried in vain to convince them to return to their duties. Meanwhile, their counterparts continue to discuss and adopt new measures to be applied under the transition. The debate is now focusing on revamping the electoral code and the creation of the Malagasy Council for Reconciliation. Parliament is discussing and approving new laws in that regard.
To overcome the political impasse, all leading forces in the country accepted to support a transitional journey based on consensus. A new government and other institutions have been formed with the support and presence of the opposition, giving an illusion of inclusiveness. In reality, President Ratsiraka's party has to date ignored the wishes of all the factions supporting the transition. Besides, there are other political forces that refuse to participate in the debate because they feel it misleading. "The current government should stop existing as it is neither consensual nor inclusive," said Brigitte Rasamoelina, chairwoman of the Malagasy Women Doing Politics party.
T he regime has snubbed the international community that brokered the roadmap agreed last year. Authorities have shown willingness to comply only partially with the agreement. For example, the accord urges the government to create favourable conditions for national reconciliation. It calls thus for the cessation of any unjust judicial pursuit, immediate release of political detainees, respect of the freedom of speech and press freedom, among others. There is no much evidence of anything happening in this neighbourhood.
Arrests, abusive detentions, trials followed by condemnations never stopped. Crackdowns against media houses were particularly frequent over the last weeks. Lalatiana Rakotondrazafy and Fidèle Razara Pierre, co-owners of Free FM radio, were kept incommunicado at a police station on 3 May: the World Press Freedom Day. Events like this raise questions about the seriousness of the establishment to walk the path of democratic debate and reconciliation.
Harassment continues against Rajoelina's allies. Some have been accused to plotting a coup against the regime. The situation is such that many decided to stand up and publicly ask for change. On May 19, a pacific rally gathering thousands of people in conflict with the regime took place in Antananarivo. As usual, military chiefs were zealous in ordering the security forces to disperse the crowd, claiming they have to protect persons and goods, and bring order in the capital. It is impossible for Madagascar to head for free and democratic elections if crackdowns on groups desiring to express their opinion continue. "An election is an occasion for people to defend their idea, to express their opinion. I'm worried as, even during the electoral campaign, the police will be ordered to disperse the crowd," sociologist André Rasolo said.
T he impoverished nation is indeed sinking further into a great socioeconomic crisis. Obvious signs are perceptible. Since January, people have protested against uncertainty and neglect with uncountable strikes. A relevant example comes from the education sector. Teachers have been protesting about the poor work conditions and falling value of salaries. They asked for a budgetary allocation of about € 50 millions. The government responded promising no more than € 6 millions, claiming the cut on the lack of financial backing from donors affected the state budget. At the same time, the state paid € 14 million to Air France for a second hand Airbus destined to Air Madagascar. In the wile, about 700,000 children cannot go to school because of poverty.
Repetitive violation of human rights lately pushed the Confederation of Christian Churches in Madagascar to express major concerns about abuses, corruption, and police violence. The body called for the respect of the fundamental values and life, a refrain repeated by the international community. It is clear that Madagascar is not walking along the way that would lead to free, transparent and credible elections.
Imalagasy Ratsimiahotra


Description: Two volumes, 12mo, 256 pp. & 251 pp. Early printing. Boards sunned, stained and worn, with some loss at edges and corners; spine soiled, chipped; corners of boards bumped; foxing to interior; dampstain affecting boards and endpapers.


text:
Q: Unable to connect to Mongodb database from heroku I created a strapi website using yarn create strapi-app velankannimatha and chose the mongo as the database. I created a DB in MongoDB atlas called velankannimathadb.
I pushed the site to Heroku after setting the config vars (i.e. DATABASE_URI and DATABASE_NAME).
But the application keeps crashing. When I checked the logs it says

Server wasn't able to start properly.
Error connecting to the Mongo database. Server selection timed out after 30000 ms

I am able to access DB locally (in development mode). It only fails when running from Heroku.
Any help is much appreciated

A: This is likely due to Mongo Atlas only allowing connections from specific IP addresses. See the docs. Although not recommended, you could make the cluster available to any IP with 0.0.0.0/0. You may also find the troubleshooting docs helpful as well.

A: You need to change the config/server.js host key from localhost to 0.0.0.0 as Strapi is trying to bind to localhost and Heroku is looking for an exposed server to "proxy"
The previous answer also is likely that your Mongo cluster does need to allow access on 0.0.0.0/0 as heroku dynos change over time and use different IPs each time.

A: It's working now. What went wrong was that I was using MongoDB version 2.2.12 or later (as per documentation). When I switched to version 3.6 or later and used the updated connection string, everything worked.
Also, adding the connection string as config vars from terminal causes issues, even if it gets saved, some characters are missing. So I added them from the browser.
This article on medium helped a lot too.

redpajama_set_name: RedPajamaStackExchange


As a junior, Maggie Tirrell was sitting in the library along the long, rectangular tables with her fellow classmates while her teacher talked about a recent book they would be reading for English. The library was a large, spacious room where many classes were held to provide more space for the lack of classrooms available at Four Rivers Charter Public School. It was a beautiful space with large rows of books to separate a class of fewer than 20 students and provide a space for diligent students at the other side of the library.
However, the shortage of classrooms was causing a undersupply of classes students could take. The only math classes that senior students could take were online or at a local community college, which was paid out-of-pocket by the student. Later that day, the school would be having an alumni/parents night to raise funding to build two more classrooms in the school.
Since 1992, charter schools have been an opportunity for disadvantaged students who lack access to quality education. They also are more effective educating students than public schools. Unfortunately, people don't realize how significantly the shortage of funding affects charter schools.
Shortage of funding is a severe problem in New York state. Researchers at the University of Arkansas discovered from their study in 2017 that New York City charter schools received less than 20 percent of funding than public schools. More research has been done to determine more recent data.
According to the Northeast Charter School Network, New York state receives 25 percent less funding than public schools. Western New York has the biggest disparity throughout the rest of the state. In Buffalo, charter schools receive less than 40 percent of funding than their public school counterparts.
Why do charter schools receive less funding?
Charter schools receive less money because public schools enroll more disabled students, who costs more money to effectively educate. In the 2009-2010 school year, charter schools had 8.2 percent of disabled students while public schools held 11.2 percent. From the University of Arkansas report, 16 percent of disabled children accounted for charter school enrollment while they accounted for 18 percent in public schools. But the enrollment numbers don't explain the funding disparity.
Low funding for charter schools has caused surprisingly significant issues for facility resources in the last few years. Most charter schools and all Western New York charter schools have to pay 12 to 15 percent of their funds toward facilities that are provided to them. According to a survey released in 10 states by the Charter Schools Facilities Initiative in 2013, about 50 percent of charter schools lack a kitchen that meets health standards to prepare meals. Half of all charter schools in Indiana, Texas and Tennessee lacked access to a gym. Tirrell's charter school is also another example that lacks a gym for physical education.
Action has been taken to provide more funding to charter schools to increase school performance. Bill Gates is one of many billionaires to give money to boost charter schools since 2006. The Bill and Melinda Gates Foundation gave the Washington Charter Schools Association $25 million to keep struggling charter schools open.
There is also a new program called the New Capital Funds Sharing program that will fund Florida charter schools $91.2 million.
With more funding, students like Tirrell will have more resources for better education.
We need to be on top of where our taxes are going if we want every child to get equal funding for their education. Charter school students need more funding for resources for easier and effective education.
Charter Schools: Efficient Education or Financial Mess?


As the name might imply, this tiny, sparsely decorated restaurant serves a mix of cuisines: Japanese, Chinese and Thai. Judging from a recent visit, it's hard to go wrong when ordering here—everything comes out of the kitchen fresh and impeccably plated. Start with one or two creative rolls, like the Crazy Tuna (black pepper tuna and avocado) or the Golden Angel (yellowtail tuna and salmon with bonito flakes), then move on to one of the delicately flavored entrées such as tender, flaky Chilean sea bass or crispy rock shrimp tempura nuggets sprinkled with roe and tossed in a creamy and spicy sauce. Desserts, including a deep-fried banana spring roll and a chocolate-fondue plate, are equally delectable.
Average main course: $13. AmEx, MC, V.


text:
Blennerhasset and Torpenhow is a civil parish in the Borough of Allerdale in Cumbria, England.  It contains 15 buildings that are recorded in the National Heritage List for England as designated listed buildings.  Of these, one is listed at Grade I, the highest of the three grades, and the others are at Grade II, the lowest grade.  The parish contains the villages of Blennerhasset and Torpenhow, and the smaller settlements of Kirkland Guards and Whitrigg, and is otherwise rural.  Most of the listed buildings are houses, cottages, farmhouses and farm buildings, the latter including buildings on a model farm.  The other listed buildings are a church, a milestone, and two war memorials.

Key

Buildings

References

Citations

Sources

Lists of listed buildings in Cumbria

redpajama_set_name: RedPajamaWikipedia


text:
APLI newsletter Vol. 18, No 1, February 2014
[gview file="http://apli.net.au/wp-content/uploads/2014/02/N1959-APLI_020114_V3-final.pdf"]
APLI newsletter, Vol 18, Issue 2, June 2014
[gview file="http://apli.net.au/wp-content/uploads/2014/06/APLI-JUNE-2014.pdf"]
APLI newsletter, Vol 3, No 2, December 2000
[gview file="http://apli.net.au/wp-content/uploads/2013/01/APLInewsltrDec20001.pdf"][gview file="http://apli.net.au/wp-content/uploads/2013/01/APLInewsltrDec2000.pdf"][gview file="http://apli.net.au/wp-content/uploads/2013/01/APLInewsltrDec2000.pdf"]
APLI newsletter, Vol 1, No 4, April 2000
[gview file="http://apli.net.au/wp-content/uploads/2013/01/April-2000.pdf"]
previous post: APLI newsletter Vol 17, No 2, Sept 2013
next post: APLI newsletter, Vol 18, Issue 2, June 2014