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Papaya

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Background & General Info

Papaya, scientifically called Carica papaya, is considered one of the most common and economically important plants worldwide, with its sweet and nutritious fruits being a widely known delicacy. Papaya originated from tropical Central America (from southern Mexico to the Andes) but has been transported to a number of regions of the tropics, principally because of Spanish exploration. [1][2] Its specialized cells termed lactifers are widespread and dispersed throughout majority of the plant’s tissues and secrete white milky latex. [3] Lately, papaya has received attention from print media, social network, and blogs as an interesting natural remedy of dengue with perceived beneficial effect on the platelet count. [4]



Botany

Papaya is a soft-wooded single-stemmed perennial tree that can attain a height of about 2–10 meters. It forms a crown consisting of large palmate leaves that arise from the apex of the trunk and has a soft, hollow, cylindrical trunk that is light green to tan brown in color and is marked with conspicuous “leaf scars”. [1][2] The large leaves are palmately lobed or deeply incised with long petioles. Borne axillary on the main stem and hanging near the trunk’s top, the green to orange fruit is a large, ellipsoidal to oblong berry that is distally rounded and contains several black seeds at its center when ripe.

History & Traditional Use

Various parts of papaya have long been traditionally used in alternative medicine for numerous ailments, including its fruit, leaves, stems, seeds, and roots. Papaya latex is prescribed in folk medicine as a remedy for dyspepsia and can be applied on external burns and scalds. Papaya fruit and its seeds are also used to eliminate helminths (i.e., worms) and amoeba. [5] As a crop, papaya is the first fruit genetically modified for human consumption. [2]

General Herbal Uses

In several tropical and industrialized countries, papaya has been widely used as a natural treatment for impaired digestion. [6] Its leaves are dried and pulverized, which are then marketed as therapeutic tea; a decoction can also be prepared from the leaves, which can be administered as treatment for disorders related to the genitourinary system. [7] Additionally, the leaves are employed as treatment for fever, diabetes, gonorrhea, syphilis, and inflammation and can be applied as a dressing for septic wounds. [1] The seeds are used to expel parasitic worms, and the roots and seeds are abortifacient. [1] In general, the latex, ripe and unripe fruits, seeds and seed juice, roots, leaves, flower, and stem bark of papaya are employed as a natural remedy with antimicrobial, anthelmentic, antimalarial, antifungal, antiamoebic, hepatoprotective, antifertility, and immunomodulatory properties. [7]



Constituents/Active Components

The latex from the stems, unripe fruits, petioles, and leaves of papaya contains a wealth of cysteine endopeptidases, namely, papain, chymopapain, glycyl endopeptidase, and caricain, with the tissues from the leaves and fruits having the highest protein contents among all by-products of papaya. [3] Rivera-Pastrana et al. (2010) identified ferulic acid (1.33–1.62 g/kg dry weight), caffeic acid (0.46–0.68 g/kg dry weight), and rutin (0.10–0.16 g/kg dry weight) as the most abundant phenolic compounds in the exocarp of ‘Maradol’ papaya fruit and lycopene (0.0015–0.012 g/kg fresh weight), β-cryptoxanthin (0.0031–0.0080 g/kg fresh weight), and β-carotene as the major carotenoids in the mesocarp. Lycopene and β-cryptoxanthin in papaya fruits stored at 25°C tend to increase during ripening. [8]

Medicinal/Scientific Research

Anticancer

Aqueous papaya leaf fraction has been shown in the study of Otsuki et al. (2010) to significantly deter the growth of numerous tumor cell lines and to exert anticancer activity. As evaluated using [(3)H]-thymidine incorporation, the addition of papaya extract enhanced the cytotoxicity of activated human peripheral blood mononuclear cells against K562 cells (human myelogenous leukemia cell line). [9] Results from a recent 2017 study demonstrated the anticancer potency of aqueous extract from papaya leaves against MCF-7 cells (human breast cancer cell line) via induction of anti-proliferation and apoptotic mechanisms. Papaya extract prevented the multiplication of human breast cancer cells and trigged their apoptosis (22.54% and 20.73% at extract concentrations of 659.63 μg/mL and 329.81 μg/mL, respectively). [10] Owing to their high polyphenol content, the black seeds of papaya have also been noted by Alotaibi et al. (2017) to diminish the growth of PC-3 cells (prostate cancer cell line). As tested using a WST-1 proliferation assay, the methanol extract obtained from the black seeds of ripe papaya had been found to reduce the proliferation of PC-3 cells. [11]

Anti-inflammatory And Immunomodulatory

Through a literature search, Pandy et al. (2016) found evidence from both in vitro and in vivo investigations regarding the anti-inflammatory and immunomodulatory properties of papaya extracts and their phytochemicals. [12] Findings from a 2010 study indicated the anti-inflammatory activity of the methanol extract from papaya seeds in experimental rats. At all doses tested, the extract effectively inhibited the inflammation (edema) induced via injection of fresh egg albumin into the hind paws of adult Wistar rats in a dose- and time-dependent manner. [13] In a 2010 Japanese study, the addition of papaya extract in human peripheral blood mononuclear cells resulted in a reduced production of interleukin-2 and interleukin-4; a boosted production of interleukin-12p40, interleukin-12p70, interferon-γ, and tumor necrosis factor-α; and an enhanced expression of 23 immunomodulatory genes. [9]

Another 2012 study orally administered a concentrate of fresh mature papaya leaves to adult Wistar rats with thrombocytopenia once daily for 3 consecutive days at doses of 0.18, 0.36, and 0.72 mL/100 g. Administration of papaya leaf concentrate at a high dose resulted in a significant inhibition of carrageenan-induced rat paw edema and impairment of vascular permeability in mice (by 82%). It also stimulated erythrocyte membrane stabilization (maximum of 10.11%) at a concentration of 8 mg/mL, suggesting effective anti-inflammatory activity. Overall, concentrate of freshly prepared mature papaya leaves has been concluded by the study to effectively but safely increase platelet, white blood cell (WBC), and red blood cell (RBC) counts in rats and to exert anti-inflammatory activity. [14]

Antibacterial

Dawkins et al. (2003) verified the antibacterial activity of ripe and unripe papaya on selected common wound bacteria. With antibacterial activity evaluated with respect to the radius of zone of inhibition, it was observed that the extract from papaya seeds inhibited the growth of the following Gram-positive and Gram-negative bacteria (ordered from the most sensitive to the least): Bacillus cereus, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, Proteus vulgaris, and Shigella flexneri. [15] A 2010 study also demonstrated the antibacterial activity of extracts derived from papaya seed, endocarp, and epicarp against isolates of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Proteus sp. in wound culture. With the antibacterial activity similarly examined in terms of zones of inhibition, Staphylococcus aureus was determined to be the most susceptible. [16]

Antiparasitic

Owing to the antihelminthic and antiamoebic activities of papaya and its seeds, air-dried papaya seeds have been advocated by Okeniyi et al. (2007) as a cheap monotherapy and preventive strategy against human intestinal parasites. In their pilot study, an elixir consisting of papaya seeds and honey, at a dose of 20 mL, was proven effective against intestinal parasitosis in 60 asymptomatic Nigerian children. Results of microscopic examinations of stools 7 days after the administration of papaya elixir indicated a clearance of parasites in the stools of 76.7% study participants, with a 71.4–100% stool clearance rate for various types of parasites. [5]

Hepatoprotective

Mohammed et al. (2011) demonstrated the ability of aqueous papaya leaf extract to protect the liver against injury induced by carbon tetrachloride in rats. Its oral administration at doses of 200 mg/kg and 400 mg/kg caused a significant dose-dependent reduction of elevated levels of serum liver enzyme markers of acute hepatocellular injury (serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), serum malondialdehyde, and bilirubin. Maximum hepatoprotection was achieved when the extract was provided at a dose of 400 mg/kg/day, which ameliorated histological changes in the liver induced by carbon tetrachloride. [17]

Impaired Digestion

In some studies, the consumption of papaya and its preparations has been clinically noted to produce favorable effects in patients suffering from constipation, heartburn, and symptoms of irritable bowel syndrome after eating papaya preparations. [6] The biologically active compounds in papaya such as papain, caricain, chymopapain, and glycine endopeptidase have been noted to improve acidic pH conditions and augment the degradation of the stomach enzyme pepsin. [7] A 2013 double-blind placebo-controlled study reported findings that indicated the clinical effects of a papaya preparation (Caricol®) and suggested its ability to support normal digestive tract physiology and to ameliorate numerous functional disturbances such as symptoms of irritable bowel syndrome. In this study, volunteers with chronic indigestion and gastrointestinal tract dysfunctions were orally administered with 20 mL of papaya preparation daily for 40 days. The intake of papaya resulted in a statistically significant improvement in constipation and bloating symptoms among study participants considered “early returnees”. [6]

Dengue

Current investigations have demonstrated the efficacy of papaya leaves in the management of dengue fever, although such purported property is still heatedly debated and discussed by the biomedical community. A recent 2016 systematic review and meta-analysis had accumulated evidence on the effectiveness and safety of papaya leaf extract in improving the clinical conditions of patients with dengue fever and hence concluded that it can be regarded as a promising natural alternative for elevating the platelet count of patients. This review analyzed the findings from four randomized controlled trials that enrolled a total of 439 subjects. In the overall analysis and analysis after the fourth day, papaya leaf extract was shown to increase platelet count, and its administration was associated with a significant decrease in hospitalization days of patients. [4]

A 2013 trial demonstrated that treatment using fresh papaya leaf extracts at a concentration of 0.2 mL significantly elevated the platelet and RBC counts in in mice. Specifically, the platelet count in the treated mice began to significantly increase at the third day (3.4 ± 0.18 × 105/µL), achieving a fourfold elevation at the 21th day (11.3 × 105/µL). The RBC count in the treated mice increased from 6 × 106/µL to 9 × 106/µL at the 21th day. [1] Admad et al. (2011) reported a case of dengue fever being effectively treated by aqueous extract obtained from papaya leaves in a 45-year-old patient. Daily administration of 25 mL of papaya leaf aqueous extract in the patient with dengue fever for 5 consecutive days led to an increase in platelet, WBC, and neutrophil count (from 55 × 103/µL to 168 × 103/µL for platelet count, from 3.7 × 103/µL to 7.7 × 103/µL for WBC count, and from 46.0% to 78.3% for neutrophil count). [7]

Contraindications, Interactions, And Safety

According to the American Herbal Products Association’s Botanical Safety Handbook, papaya is categorized as an ethnomedicine with safety class 2B status (an herb not to be used during pregnancy), with no known drug and supplement interactions or associated adverse events. [18] In the study of Okeniyi et al. (2007), papaya elixir administration produced no harmful effects. [5] Findings from a 2012 study also associated the 3-day administration of mature papaya leaf concentrate at a high dose with an absence of overt signs of toxicity. [14] In some Asian countries, the consumption of papaya is contraindicated during pregnancy, especially the unripe or semi-ripe papaya, which contains copious amounts of latex that can trigger marked uterine contractions in a pregnant woman. The roots and seeds of papaya can also induce abortion. [1] However, a 2002 Singaporean study provided results that confirmed the safety of normal consumption of ripe papaya during pregnancy. Groups of Sprague-Dawley rats at different stages of gestation (days 1–5, 6–11, 12–17, and 18–20 that freely received ripe papaya blend at a concentration of 500 mL for every liter of water manifested no signs of fetal or maternal toxicity. Papaya consumption did not also significantly affect the number of implantation sites and viable fetuses in rats. The in vitro study also confirmed that consumption of 0.1–0.8 mL ripe papaya juice did not lead to any significant contractile effect on the uterine smooth muscles of pregnant and non-pregnant rats. [19]

References:

[1] S. L. C. A. Dharmarathna, S. Wickramasinghe, R. N. Waduge, et al., "Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model," Asian Pacific Journal of Tropical Biomedicine, vol. 3, no. 9, p. 720–724, 2013. http://www.sciencedirect.com/science/article/pii/S2221169113601458

[2] M. Rieger, "Papaya - Carica papaya," Fruit Crops. www.fruit-crops.com/papaya-carica-papaya/

[3] G.-E. Thomás, H.-G. Rodolfo, M.-D. Juan, et al., "Proteolytic activity in enzymatic extracts from Carica papaya L. cv. Maradol harvest by-products," Process Biochemistry, vol. 44, no. 1, p. 77–82, 2009. http://www.sciencedirect.com/science/article/pii/S1359511308002900

[4] J. Charan, D. Saxena, J. P. Goyal and S. Yasobant, "Efficacy and safety of Carica papaya leaf extract in the dengue: A systematic review and meta-analysis," International Journal of Applied and Basic Medical Research, vol. 6, no. 4, p. 249–254, 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108100/

[5] J. Okeniyi, T. Ogunlesi, O. Oyelami and L. Adeyemi, "Effectiveness of dried Carica papaya seeds against human intestinal parasitosis: a pilot study," Journal of Medicinal Food, vol. 10, no. 1, p. 194–196, 2007. https://www.ncbi.nlm.nih.gov/pubmed/17472487

[6] C. Muss, W. Mosgoeller and T. Endler, "Papaya preparation (Caricol®) in digestive disorders," Neuroendocrinology Letters, vol. 34, no. 1, p. 38–46, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23524622

[7] N. Ahmad, H. Fazal, M. Ayaz, et al., "Dengue fever treatment with Carica papaya leaves extracts," Asian Pacific Journal of Tropical Biomedicine, vol. 1, no. 4, p. 330–33, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614241/

[8] D. Rivera-Pastrana, E. Yahia and G. González-Aguilar, "Phenolic and carotenoid profiles of papaya fruit (Carica papaya L.) and their contents under low temperature storage," Journal of the Science of Food and Agriculture, vol. 90, no. 14, p. 2358–2365, 2010. https://www.ncbi.nlm.nih.gov/pubmed/20632382

[9] N. Otsuki, N. Dang, E. Kumagai, A. Kondo, et al., "Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects," Journal of Ethnopharmacology, vol. 127, no. 3, p. 760–767, 2010. https://www.ncbi.nlm.nih.gov/pubmed/19961915

[10] F. Z. Nisa, M. Astuti, A. Murdiati and S. M. Haryana, "Anti-proliferation and apoptosis induction of aqueous leaf extract of Carica papaya L. on human breast cancer cells MCF-7," Pakistan Journal of Biological Sciences, vol. 20, no. 1, p. 36–41, 2017. https://www.ncbi.nlm.nih.gov/pubmed/29023013

[11] K. Alotaibi, H. Li, R. Rafi and R. Siddiqui, "Papaya black seeds have beneficial anticancer effects on PC-3 prostate cancer cells," Journal of Cancer Metastasis and Treatment, vol. 3, p. 161–168, 2017. http://jcmtjournal.com/article/view/2224

[12] S. Pandey, P. J. Cabot, et al., "Anti-inflammatory and immunomodulatory properties of Carica papaya," Journal of Immunotoxicology, vol. 13, no. 4, p. 590–602, 2016. https://www.ncbi.nlm.nih.gov/pubmed/27416522

[13] L. Amazu, C. Azikiwe, C. Njoku, et al., "Antiinflammatory activity of the methanolic extract of the seeds of Carica papaya in experimental animals," Asian Pacific Journal of Tropical Medicine, vol. 3, no. 11, p. 884–886, 2010. http://www.sciencedirect.com/science/article/pii/S199576451060212X

[14] A. Gammulle, W. Ratnasooriya, J. Jayakody, et al., "Thrombocytosis and anti-inflammatory properties, and toxicological evaluation of Carica papaya mature leaf concentrate in a murine model," International Journal of Medicinal Plants Research, vol. 1, no. 2, p. 21–30, 2012. https://www.researchgate.net/profile/Preethi_Udagama2/publication/251237485_Thrombocytosis_and_Anti-inflammatory_Properties_and_Toxicological_Evaluation_of_Carica_papaya_Mature_Leaf_Concentrate_in_a_Murine_ModelLinkEditRe-order_section/links/0a85e537b53ec86b63000000/Thrombocytosis-and-Anti-inflammatory-Properties-and-Toxicological-Evaluation-of-Carica-papaya-Mature-Leaf-Concentrate-in-a-Murine-ModelLinkEditRe-order-section.pdf

[15] G. Dawkins, H. Hewitt, Y. Wint, et al., "Antibacterial effects of Carica papaya fruit on common wound organisms," West Indian Medical Journal, vol. 52, no. 4, p. 290–292, 2003. https://www.ncbi.nlm.nih.gov/pubmed/15040064

[16] C. Akujobi, C. Ofodeme and C. Enweani, "Determination of antibacterial activity of Carica papaya (pawpaw) extracts," Nigerian Journal of Clinical Practice, vol. 13, no. 1, 2010. https://www.ajol.info/index.php/njcp/article/view/53187

[17] A. Mohammed, S. Abubakar and M. Sule, "Hepatoprotective effect of aqueous leaf extract of Carica papaya Linn. against CCL 4-induced hepatic damage in rats," International Journal of Pharmaceutical Sciences Review and Research, vol. 11, p. 13–16, 2011. https://www.researchgate.net/publication/287883795_Hepatoprotective_effect_of_aqueous_leaf_extract_of_Carica_papaya_Linn_against_CCL_4-induced_hepatic_damage_in_rats

[18] Z. Gardner and M. McGuffin, American Herbal Products Association’s Botanical Safety Handbook, Boca Raton: CRC Press, 2013.

Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018

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