Food Therapy: Fruits - Papaya

Kyle J. Norton(Scholar and Master of Nutrients, all right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.


                         Papaya


Papaya is a species of Carica Papaya, belongs to the family Caricaceae and native to the tropics of the Americas, and was first cultivated in Mexico and several centuries

Nutritients
1. Carbohydrates
2. Sugars
3. Fiber
4. Protein
5. Vitamin A
6. Thiamine (Vitamin B1)
7. Riboflavin (Vitamin B2)
8. Niacin (Vitamin B3)
9. Vitamin B6
10. Vitamin C
11. Vitamin E
12. Vitamin K
13. Calcium
14. Iron
15. Magnesium
16. Phosphorus
17. Potassium
18. Sodium
19. Etc.

Chemical constituents
Alkaloids, Cardenolides, Anthraquinones, Saponins, Tannin, phenol, flavonoid, anthocyanin, Benzyl glucosinolate, benzylisothiocyanate, 5-(Hydroxymethyl)-2-furancarboxaldehyde, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one and 1,3-dihydroxy-2-propanone, etc.(a)


1. Papaya and cancers
Although with no clinical or animal cancer studies but in vitro, papaya extract may be the next potential pharmacological target to identify the ingredients for treatment of cancers(2). According to the World center fund International, in 2012, there was 14.1 million cancer cases, affecting 7.4 million in men and 6.7 million in women. This number is expected to increase to 24 million by 2035(3).

Its nutrients including Vitamin A, Thiamine (Vitamin B1), Riboflavin (Vitamin B2), Niacin (Vitamin B3), Vitamin B6, Vitamin C, Iron, Magnesium, Phosphorus, Potassium, etc. and major chemical constituent and ethanol extract including benzylisothiocyanate are said to exhibit immunomodulatory, anti-inflammatory, anti hyperlipidemic, anti cellular oxidative stress, anti neural tube defect, etc. effects(1).

Papaya, a species of Carica Papaya, belonging to the family Caricaceae, native to the tropics of the Americas, has been used in traditional medicine as remedies for many various ailments, including gastric problems, inflammation, and cancer(12).

Aqueous extract, according to University of Tokyo, on various tumor cell lines, showed to inhibit significant growth activity, through immunomodulatory effects including, interleukin 12 (also known as natural killer cell stimulatory factor 2), IL-12p70(a heterodimer), IFN-gamma(regulation of immunologically relevant genes) and TNF-alpha(innate immune response against viral infection)(4).

Fermented papaya, a traditional dish of many Southeast Asian cultures, is said to process antioxidant and immune-modulating potentials, through influence of signaling cascades associated with cell growth and survival, from epidemiological and in-vitro studies of patient with diabetes(5). In Azoxymethane (AOM) induced colon cancer in rats, papaya peel extract (PapPE), showed a significantly ameliorated the cytotoxic effects of AOM, through its potent anti-oxidant activities in reduction of oxidative stress (glutathione depletion, lipid peroxidation)(6).

In cultured human lung cancer H69 cell, Benzyl glucosinolate (BG) found in the pulp and the seed of papaya, inhibit the cancer cell proliferation in an administration of doses of 6.5 μmol(7), probably through its effect in superoxide generation and apoptosis induction(8).
Benzylisothiocyanate (BITC) found in papaya, also mediated apoptosis of prostate and pancreasescancer cells through activation both procaspase-8 pathways(initiation of apoptosis) and cell cycle arrest(9), inhibited advanced ovarian cancer cell lines through activation of caspase-3(activation in the apoptotic cell) and -9(activation of apoptotic process), and cleavage of PARP-1(repair of DNA damage)(10) and breast cancer through generation of reactive oxygen species and cleavage of caspase-9, caspase-8, and caspase-3(11)

Taken altogether, fermented papaya and it major chemical constituents such as Benzyl glucosinolate (BG) and Benzylisothiocyanate (BITC) may be effective in reduced risk and treatment for certain types of cancer, but further studies with large sample size and muti centers are necessary to identify the main ingredients in comparison of currently pharmacological medicine use to improve its validation. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying

References
(1) #Healthy #Foods - Fruits - Papaya (Carica Papaya)(Better living and living health)
(2) Anticancer activity of Carica papaya: a review by Nguyen TT1, Shaw PN, Parat MO, Hewavitharana AK.(PubMed)
(3) Cancer statistics Worldwide(World center fund International)
(4) Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects by Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C.(PubMed)
(5) Diabetes as a risk factor to cancer: Functional role of fermented papaya preparation as phytonutraceutical adjunct in the treatment of diabetes and cancer by Aruoma OI, Somanah J, Bourdon E, Rondeau P, Bahorun T(PubMed)
(6) Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts by Waly MI, Al-Rawahi AS, Al Riyami M, Al-Kindi MA, Al-Issaei HK, Farooq SA, Al-Alawi A, Rahman MS.(PubMed)
(7) Content determination of benzyl glucosinolate and anti-cancer activity of its hydrolysis product inCarica papaya L, by Li ZY1, Wang Y, Shen WT, Zhou P.(PubMed)
(8) Papaya seed represents a rich source of biologically active isothiocyanate by Nakamura Y, Yoshimoto M, Murata Y, Shimoishi Y, Asai Y, Park EY, Sato K, Nakamura Y.(PubMed)
(9) Dietary isothiocyanate mediated apoptosis of human cancer cells is associated with Bcl-xL phosphorylation by Basu A, Haldar S.(PubMed)
(10) Benzyl isothiocyanate (BITC) induces apoptosis in ovarian cancer cells in vitro by Kalkunte S, Swamy N, Dizon DS, Brard L(PubMed)
(11) Benzyl isothiocyanate-induced apoptosis in human breast cancer cells is initiated by reactive oxygen species and regulated by Bax and Bak by Xiao D1, Vogel V, Singh SV.(PubMed)
(12) Ficus carica L. (Moraceae): Phytochemistry, Traditional Uses and Biological Activities by Mawa S, Husain K, Jantan I.(PubMed)


2. Carica papaya and diabetes
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

Water extract from papaya, through inhibition of enzymes, α-amylase and α-glucosidase linked to type 2 diabetes, in sodium nitroprusside (SNP)-induced lipid peroxidation in rat pancreas in vitro, and in a dose-dependent manner(1) and reduced oxidative stress in Fe²⁺-induced oxidative stress in rat pancreas(2). Carica papaya leaves in streptozotocin-induced diabetic rats, according to Universidad Juárez Autónoma de Tabasco (UJAT), not only exert hypoglycemic effects in both animals and humans studies, but also help islet regeneration manifested as preservation of cell size as well as prevented hepatocyte disruption(3), as well as controlled blood glucose levels and improved lipid profile in diabetic rats(4). In short term supplementation of a fermented papaya, showed to exhibit its effect in management of diabetes and for those at risk for cardiovascular disease, neurological disease and other conditions worsened by overt inflammation and oxidative stress(5).



References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR1, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water-extractable phytochemicals from unripe pawpaw fruit (Carica papaya). by Oboh G, Olabiyi AA, Akinyemi AJ, Ademiluyi AO.(PubMed)
(2) Inhibitory effect of aqueous extract of different parts of unripe pawpaw (Carica papaya) fruit on Fe²⁺-induced oxidative stress in rat pancreas in vitro by Oboh G1, Olabiyi AA, Akinyemi AJ.(PubMed)
(3) Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats by Juárez-Rojop IE1, Díaz-Zagoya JC, Ble-Castillo JL, Miranda-Osorio PH, Castell-Rodríguez AE, Tovilla-Zárate CA, Rodríguez-Hernández A, Aguilar-Mariscal H, Ramón-Frías T, Bermúdez-Ocaña DY.(PubMed)
(4) Antihyperglycemic and hypolipidemic activities of aqueous extract of Carica papaya Linn. leaves in alloxan-induced diabetic rats by Maniyar Y1, Bhixavatimath P(PubMed)
(5) Effects of a short term supplementation of a fermented papaya preparation on biomarkers ofdiabetes mellitus in a randomized Mauritian population by Somanah J1, Aruoma OI, Gunness TK, Kowelssur S, Dambala V, Murad F, Googoolye K, Daus D, Indelicato J, Bourdon E, Bahorun T.(PubMed)

3. Carica papaya and cholesterol
Cholesterol is needed for our body to build cell walls, make hormones and vitamin D, and create bile salts that help you digest fat. However too much of it can be dangerous because cholesterol cannot dissolve in your blood
Ficus carica leaf extract modulates, on hyperlipidemia in high fat diet (HFD)-induced obese male rats, showed to improve the lipid profile and decreased adipogenic risk factors, most likely mediated through an increase in HDL-C levels(1) and streptozotocin-induced diabetic rats, it also exerted hypoglycemic and antioxidant effect;, through improved the lipid profile and affected integrity and function of both liver and pancreas(2). Ether- and water-soluble fractions of Carica papaya ethanol extract, on the other hand, in dose-dependent manner inhibited the total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL) level, and significantly increased high-density lipoprotein (HDL) level(3). Unfortunately, according to the Institute for Medical Research, C. papayaleaf extract at a dose over fourteen times the levels employed in practical use in traditional medicine may induce toxicity(4).


References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR1, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Ficus carica leaf extract modulates the lipid profile of rats fed with a high-fat diet through an increase of HDL-C by Joerin L1, Kauschka M, Bonnländer B, Pischel I, Benedek B, Butterweck V.(PubMed)
(2) Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats by Juárez-Rojop IE1, Díaz-Zagoya JC, Ble-Castillo JL, Miranda-Osorio PH, Castell-Rodríguez AE, Tovilla-Zárate CA, Rodríguez-Hernández A, Aguilar-Mariscal H, Ramón-Frías T, Bermúdez-Ocaña DY.(PubMed)
(3) Effect of ether- and water-soluble fractions of Carica papaya ethanol extract in experimentally induced hyperlipidemia in rats by Iyer D1, Sharma BK, Patil UK.(PubMed)
(4) Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats by Afzan A1, Abdullah NR, Halim SZ, Rashid BA, Semail RH, Abdullah N, Jantan I, Muhammad H, Ismail Z.(PubMed)

4. Papaya and hypertension
Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. High blood pressure means raising pressure in your heart.If it stays high over time it can damage the body in many ways.
Carica papaya, according to the Faculty of Medicine and Health Sciences Universiti Putra Malaysia, in alpha-amylase inhibition assay, may consist a nutraceutical potential ofor hyperglycemia andhypertension prevention associated with type 2 diabetes(1). Fruit juice of Carica papaya (L.) study, in the testing of Male albino Wistar rats, exhibited anti hypertensive effective through activation of alpha-adrenoceptor(2). According to University of Naples "Federico II", papaya might interact with Warfarin, the most common cardiovascular drug(3).

References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR1, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) In vitro inhibitory potential of selected Malaysian plants against key enzymes involved in hyperglycemia and hypertension by Loh SP1, Hadira O.(PubMed)
(2) Blood pressure depression by the fruit juice of Carica papaya (L.) in renal and DOCA-inducedhypertension in the rat by Eno AE1, Owo OI, Itam EH, Konya RS.(PubMed)
(3) Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction by Izzo AA1, Di Carlo G, Borrelli F, Ernst E.(PubMed)


5. Papaya and Cellular oxidative stress
In Azoxymethane (AOM) induced oxidative stress and carcinogenesis in rat colon and oxidative stress-induced insult in human SH-SY5Y neuronal cells, papaya peel extract (PapPE) and papayaepicarp extract (PEE) showed to significantly ameliorated the cytotoxic effects through its potent anti-oxidant activities(1)(2)as well as in reducing the neurological health diseases associated with various oxidative stress insults(3). Fermented papaya preparation (FPP), according to Hadassah-Hebrew University Medical Center, exhibited ROS scavenging effect on blood cells in vitro or in vivo (in thalassemic patients and experimental animals), through its related antioxidant mechanism, at least in part, to iron chelation(4).

References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR1, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts by Waly MI, Al-Rawahi AS, Al Riyami M, Al-Kindi MA, Al-Issaei HK, Farooq SA, Al-Alawi A, Rahman MS1.(PubMed)
(2) Papaya epicarp extract protects against aluminum-induced neurotoxicity by Waly MI1, Guizani N, Ali A, Rahman MS.(PubMed)
(3) Papaya epicarp extract protects against hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuronal cells by Guizani N1, Waly MI, Ali A, Al-Saidi G, Singh V, Bhatt N, Rahman MS.(PubMed)
(3) The antioxidant effect of fermented papaya preparation involves iron chelation by Prus E1, Fibach E.(PubMed)

6. Papaya and Anemia
Anemia is characterized by deficiency in the hemoglobin of the red blood cells diminishing the ability of the blood to transport oxygen to our cells and to removing carbon dioxide.
Sickle cell disease (SCD) is a genetic disease associated with unusually large numbers of immature blood cells. According to Covenant University, Methanolic extracts from S. monostachyus, C. papaya seed oil, exhibited particular antisickling properties coupled with the potential to reduce stress in sickle cell patients(1). In In beta-hemoglobinopathies, fermentedpapaya preparation (FPP), increased the content of reduced glutathione (GSH) in red blood cells(RBC), and decreased their reactive oxygen species (ROS) generation, membrane lipid peroxidation, and externalization of phosphatidylserine (PS), indicating amelioration of their oxidative status, without a significant change in the hematological parameters, probably through addition of an iron chelator(2) and alleviated symptoms associated with oxidative stress in severe forms of thalassemia(3) as well as significant reduction in the number of sickle cells(4).

References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR1, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Solenostemon monostachyus, Ipomoea involucrata and Carica papaya seed oil versus Glutathione, or Vernonia amygdalina: methanolic extracts of novel plants for the management of sickle cell anemia disease by Afolabi IS1, Osikoya IO, Fajimi OD, Usoro PI, Ogunleye DO, Bisi-Adeniyi T, Adeyemi AO, Adekeye BT.(PubMed)
(2) Amelioration of oxidative stress in red blood cells from patients with beta-thalassemia major and intermedia and E-beta-thalassemia following administration of a fermented papaya preparation by Fibach E1, Tan ES, Jamuar S, Ng I, Amer J, Rachmilewitz EA.(PubMed)(3) Fermented papayapreparation as redox regulator in blood cells of beta-thalassemic mice and patients by Amer J1, Goldfarb A, Rachmilewitz EA, Fibach E(PubMed)
(4) Preliminary in vitro antisickilng properties of crude juice extracts of Persia Americana, Citrus sinensis, Carica papaya and Ciklavit® by Iweala EE1, Uhegbu FO, Ogu GN.(PubMed)

7. Papaya and anti inflammatory effects
The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases.
According to Universiti Putra Malaysia, papaya exhibited anti inflammatory effects through T cells
regulated regulation through suppression of inflammatory cytokines(1). Mangiferin (MF), a natural glucosyl xanthone found in papaya showed a significant protection against sepsis-induced ALI through inhibiting inflammatory signaling and proinflammatory mediators(2). Fermented papayapreparation, a functional food supplement, in the study of Touro College of Pharmacy exhibited anti-inflammatory, antioxidant, immunostimulatory (at the level of the mucus membrane) and induction of antioxidant enzymes(3).

References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR1, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)(1) Carica papaya increases regulatory T cells and reduces IFN-γ+ CD4+ T cells in healthy human subjects by Abdullah M1, Chai PS, Loh CY, Chong MY, Quay HW, Vidyadaran S, Seman Z, Kandiah M, Seow HF.(PubMed)
(2) Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1 by Gong X1, Zhang L, Jiang R, Ye M, Yin X, Wan J.(PubMed)
(3) Applications and bioefficacy of the functional food supplement fermented papaya preparation by Aruoma OI1, Hayashi Y, Marotta F, Mantello P, Rachmilewitz E, Montagnier L.(PubMed)
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