Medicinal Properties of Carica papaya
Plants with healing properties are utilized in folk medicine and, since remote times, have been considered traditional therapeutic approaches that have effects on health. They are also advantageous from a cost–benefit point of view. Synthetic drugs used to be the first option for the treatment of several diseases. However, because of the adverse effects shown by long- or even short-term consumption, studies aiming at the use of alternative therapies in the treatment and prevention of diseases have increased considerably.
One alternative therapy includes the use of nutraceuticals, which, in turn, according to the existing regulations, cannot be categorized or defined either as food or a drug, but can be understood in the category of food supplements, with beneficial properties for health maintenance, in particular for some pathologic conditions. Therefore, a therapeutic approach, based on nutraceuticals for maintenance of health, resulted in a worldwide “nutraceutical revolution”.
Among plants with beneficial properties on health is Carica papaya, the well-known papaya. This fruit contains considerable concentrations of vitamins, bioactive compounds and a lipidic composition that reduces inflammatory markers and anti-platelet aggregation, protects against thrombogenesis and oxidative stress, and prevents hypercholesterolemia—factors that can be triggered by obesity.
Carica papaya is a popular fruit, and its largest production occurs in tropical and subtropical regions. According to the Food and Agriculture Organization of the United Nations (FAO), over 6.8 million tons of the fruit are produced in the world annually, ca. 440 thousand ha. Central and South America, especially Brazil, are responsible for 47% of the fruit yield, produced year round, being an important source of nutrients with a low cost and great availability in the market.
Carica papaya is consumed worldwide, either in natura or processed as jam, sweets and pulp, and to aggregate the nutritional value, other parts of the plant (leaves and seeds) are added to some products in the form of teas and flours. The pulp composition presents three important sources of vitamins with potential antioxidant action, A, C and E, besides minerals, such as magnesium and potassium, and B complex vitamins, such as pantothenic acid and folate, as well as the presence of food fibers. Besides these nutrients, papaya contains the enzyme papain, effective in increasing intestinal motility and transit time, and is also utilized in the treatment of traumas, allergies and sport lesions. Some studies observed the presence of proteolytic enzymes, such as chymopapain, with anti-viral, antifungal and antibacterial properties.
The seed contains phenolic compounds, such as benzyl isothiocyanate, glucosinolates, tocopherols (α and δ), β-cryptoxanthin, β-carotene and carotenoids, while the seed oil principally presents oleic fatty acid, followed by palmitic, linoleic and stearic acids. The leaves have a high content of food fibers and polyphenolic compounds, such as flavonoids, saponins, pro-anthocyanins, tocopherol and benzyl isothiocyanate.
The tree C. papaya is native to Central and South America and is one of the most cultivated fruit plants in the world, especially in tropical and subtropical areas. It is a herbaceous perennial plant, with a milky latex that can reach 12 m in height. It has a year-round fruit production, and each fruit weighs between 1000 and 3000 g.
The fruit of C. papaya is considered one of the most common fruits in relation to human consumption and provides a favorable cost benefit in consideration of its nutritional value, with a low caloric content and rich concentration of vitamins and minerals.
Different parts of the C. papaya plant, such as the fruits, seeds, roots, leaves, stem and latex were found to have important bioactive compounds, which, in turn, may exert medicinal effects. The methanolic extract of unripe fruits exerted antioxidant activity in vivo, for the presence of compounds, such as quercetin and β−sitosterol. Other studies detected considerable quantities of total phenols (203 mg·100 g−1 extract) in the methanolic extract of the papaya pulp, while terpenoids, alkaloids, flavonoids and saponins were identified in the water extract. Besides, in papaya seed extracts, the presence of benzyl isothiocyanate and expressive quantities of glucosinolates were observed.
Evaluating the oil extracted from the seeds, the main quantified fatty acid was oleic acid (71.30%), followed by palmitic (16.16%), linoleic (6.06%), and stearic acids (4.73%). The predominant tocopherols were α and δ-tocopherol, with 51.85 and 18.9 mg·kg–1, respectively. The β-cryptoxanthin (4.29 mg·kg–1) and β-carotene (2.76 mg·kg–1) were the quantified carotenoids, and the content of total phenolic compounds was 957.60 mg·kg–1 .
Studies showed that C. papaya leaves present tocopherol, lycopene, flavonoids and benzyl isothiocyanate. Another important study demonstrated that the phytochemical composition of ethanolic, methanolic, acetate and water extracts of C. papaya leaves is independent of the type of extract, detecting polyphenols, flavonoids, saponins and pro-anthocyanins, besides the antioxidant activity, evaluated by the method 1,1-diphenyl-2-picrylhydrazyl (DPPH). However, the water extract had superior values of polyphenols (23.1 mgGAE/g) and antioxidant activity (166 µgTE/g), while the ethanolic extract had the highest concentrations of flavonoids (17.1 mgCE/g), saponins (82.8 mgAes/g) and pro-anthocyanins (7.91 mgCE/g)
Carica papaya contains important nutrients and bioactive compounds, such as antioxidants, vitamins, and minerals, with nutraceutical characteristics and potential beneficial effects on health . Studies evaluated the actions of C. papaya in recovery from drug-induced hepatoxicity in rodents , e.g., by carbon tetrachloride (CCl4), considered a potent inducer of toxic effects in the liver for being highly metabolized in bodily tissues because of the high reactivity of halogenated metabolites (CCl3 and Cl), and such activation of metabolites liberate the active oxygen species (ROS). Another drug in question was acetaminophen (600 mg·100 g−1 ), an analgesic and anti-pyretic, which causes acute hepatocellular damage that can be lethal if not treated .
Among the main effects that extracts of different parts of C. papaya demonstrated, in recovery from toxic effects on the liver, are the decrease in hepatic damage with the increase in antioxidant enzymes such as superoxide dismutase (SOD), glutathione (GSH), and catalase in the liver and decreases in the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Similar data were observed in nephrotoxicity induced by CCl4 in rats treated with C. papaya seed water extract, depending on the dose and time of treatment. The results showed a drop in biochemical parameters, such as the serum levels of uric acid, urea, and creatinine, besides the renal protecting ion, constated by histological evaluation after recovery from renal lesions.
Besides the effects on hepatic and renal toxicity, C. papaya displayed antimicrobial , anti-amoebic , anti-parasitic , and anti-malaria actions. The use of C. papaya leaf water extract at different concentrations (25, 50, 100, 200 mg·mL−1 ) had antimicrobial activity on the inhibition of some human pathogens, such as Escherichia coli, Pseudomonas aeruginosa, Kleibseilla pneumoniae, Staphylococcus aureus, and Proteus mirabilis . Another study, utilizing the same type of extract at the dose of 100 mg·mL−1 found anti-amebic activity against Entamoeba histolytica . Furthermore, C. papaya seeds had an activity on human intestinal parasites (Caernorhabditis elegans), without considerable side effects, owing to the presence of B-benzylisothiocyanate, a potent anti-helminthic . Studies have shown the inhibitory effects on Plasmodium falciparum (malaria) in vitro, while the extract from the green fruit pulp of C. papaya demonstrated the highest anti-malaria activity, in comparison with different extracts of other tested plants.
Other studies showed the action of the water extract of C. papaya leaves (20 mg·mL−1 ) on proliferation inhibition in strains of solid tumor cells in trials in vitro, e.g., cervical carcinoma (Hela), breast adenocarcinoma (MCF-7), hepatocellular carcinoma (HepG2), lung adenocarcinoma (PC14), pancreatic carcinoma (Panc-1) and mesothelioma (H2452) in a dose-dependent manner, suggesting the anti-tumoral action of the extract. To determine whether the proliferation inhibition was associated with decreased cell viability, the water extract of C. papaya leaves was shown to inhibit proliferation responses of hematopoietic cell strains, including T-cell lymphoma (Jurkat), plasma cell leukemia (ARH77), Burkitt’s lymphoma (Raji), and large-cell anaplastic lymphoma (Karpas-299). In addition, the C. papaya leaf extract showed immunomodulatory activity on peripheral human blood mononuclear cells.
Antiulcerogenic actions were verified with the use of C. papaya seed water extract (50–100 mg/kg), the same action being observed using the methanolic extract, showing gastro-protective activity in animals, in both prevention and treatment models of gastric ulcer. In addition, the C. papaya seed extract was able to reduce the contractility of rabbit jejunum smooth muscle—the responsible compound being benzyl isothiocyanate.
Effective anti-inflammatory actions were verified by applying C. papaya leaf ethanolic extract (25–250 mg·kg−1 ) on carrageenan-induced paw edema in rats. However, after the ulcerogenic activity tests, the extract with the highest concentration produced a mild irritation of the gastric mucosa. Besides the effects on inflammation, C. papaya showed wound healing properties. It is known that diabetic patients often have persistent difficulty in healing and require the delicate handling of wounds, demanding appropriate care. The topical use of the water extract of green fruits of C. papaya on wounds in diabetic rats, induced by streptozotocin (STPZ, 50 mg·kg−1 ), exhibited a 77% reduction of the wound, induced by excision, with faster epithelization, compared with the control group, which received Vaseline