Nutritional and Phyto-Therapeutic Potential of Papaya (Carica Papaya Linn.): An Overview

Abstract

Carica papaya is an economically vivacious plant of tropical and subtropical regions, cultivated in over 50 countries across the world with 6.8 million tons production. Papaya holds a broad spectrum of phytochemicals, including polysaccharides, vitamins, minerals, enzymes, proteins, glycosides, saponins, flavonoids, and phytosterols. These bioactive components are responsible for the pharmacological properties of this auspicious plant and demonstrate its importance in daily intake and alimentation. Additionally, it is an excellent aid to digestion and also hydrolyzing gluten, which is an important aspect for dyspeptic and celiac disease patients. Papaya acts as an antioxidant, antimicrobial, anticarminative, anticancer, and has hepato-protective, immunological, and other therapeutic attributes. The seed and pulp of papaya have bacteriostatic effects against several enteropathogens, such as Bacillus subtilus and E. coli. In the current review, pharmacological attributes, nutritional value of papaya, and medicinal properties of its various parts have been elaborated to provide collective information on this multipurpose commercial plant. Moreover, its role in the production of alcohol and carboxymethyl cellulose is also the limelight of the article. Furthermore, the present review article summarizes the literature pertaining to its pharmakinetics and also allies its health claims. Yet, the authors are still of the view that further research needs to be conducted for meticulousness.

Keywords:

• Papaya
• Phytochemicals
• Functional food
• Anti-cancer
• Dengue fever

INTRODUCTION

The papaya (Carica papaya Linn.) is an evergreen plant found in tropical regions,^[1] originated from Central America and Mexico.^[2,3] Few reports support that it is originated from the northwest of South America.^[4,5] Papaya is a herbaceous succulent plant that possesses a self-supporting stalk.^[6] It may be male, female, or hermaphrodite,^[7] reproducing by self-pollination.^[8] Its fruit is a berry, produced from syncarpous superior ovary by parietal placentation.^[9,10] For being used as an edible fruit, it is extensively cultivated for export and household utilization.^[11]

Papaya, an economically imperative crop of tropical and subtropical regions,^[12] is cultivated in over 50 different countries of the world.^[13] It is estimated that over 6.8 million tonnes of fruit were produced worldwide in 2004 on about 389,990 hectares of land.^[14] Globally, production of papaya has been raised to about 40% in a decade (1998–2008), with 9.1 million tonnes production during the year 2008. The leading producers of papaya are Brazil (world’s biggest producer), Mexico, and Nigeria.^[11] Nigeria is the third largest producer worldwide with an estimated production of 765,000 metric tonnes.^[14] South America contributes 65% of the global production however; the remaining 35% is contributed by North Central America and Africa (Table 1).

Carica Papaya L. is pronounced differently in various localities. For instance, the Arabic name for papaya is “babaya,” while in English, French, German, and Hindi languages it is called pawpaw/papaya, papailler, melonenbraum, and papeeta, respectively.^[15] Moreover, nutritional and functional aspects of papaya related to diet therapy for various maladies and the findings on its medicinal properties have also been discussed.

NUTRITIONAL AND PHYTOCHEMICAL PROFILE

The chemical evaluation of papaya revealed the presence of potassium (223 mg/100 g of fresh fruit) along with sodium, calcium, phosphorus, zinc, iron, copper, manganese, and magnesium in appreciable amounts. Papaya occupies a key position among the fruits for vitamin A, C, B₁, and B₂, thiamine, folate, riboflavin, niacin, calcium, potassium, iron, and fiber contents. It is low in calories, but rich in vitamins and minerals. About 60% of the ripe fruit is edible per 100 g of fruit. The energy value of papaya is 200 kJ/100 g. The main sugars include glucose (29.8 g/100 g), fructose (21.9 g/100 g), and sucrose (48.3 g/100 g). About 100 g of fresh fruit endows with 108 mg of ascorbic acid; which is higher than oranges (67 mg/100 g of fresh fruit).^[16]

The sensory traits, like taste and aroma, are due to volatile compounds, i.e., hydrocarbons, alcohols, terpenes, aldehydes, ketones, esters, benzyl isothiocyanate, and organic acids.^[17,18] However, fruit aroma is related to ethyl hexaonate, ethyl 2-methylbutanoate and ethyl acetate.^[19,20] Aliphatic and aromatic hydrocarbons are those groups that are found to be present at higher levels and are major contributors for aroma.^[21] Linalool is the papaya’s highly abundant volatile^[21] and 94% in Solo papaya varieties. On the other hand, in Taiwan varieties the oxide cis-linalool is abundant; linalool ranks second highest in concentration.^[22] It has been investigated that aromatic compounds, such as 3-methylbutanol, butanol, terpineol, and benzyl alcohol, become abundant at the ripe stage.^[17] It has been noted that among 103 esters, methyl butyrate is the peak in papaya.^[23] A variety of compounds other than linalool, are also present in fruit, i.e., benzyl isothiocyanate^[21,24] and terpene hydrocarbons. Butanol, 3-methylbutanol, benzyl alcohol, and α-terpineol show maximum concentration in the third maturation stage, in connection with fruit ripeness.^[25]

The flesh color of papaya fruit is considered to be a significant nutritional quality attribute.^[26] Softness and development of amber to orange color are characteristics of ripe fruit. Its flavor is alike to cantaloupe; it is sweet and juicy, includes some muskiness,^[27] and its pulp can achieve 10–11.5% total soluble solids (TSS). Phenolic compounds that are present in the fruit skin are likely to decrease as ripening progresses. The following compounds have been identified, i.e., ferulic acid (277.49 to 186.63 mg/100 g of fresh fruit), p-coumaric acid (229.59 to 135.64 mg/100 g fresh fruit), and caffeic acid (175.51 to 112.89 mg/100 g). On the other hand, the following carotenoids in flesh along with vitamin C increases with ripening; lycopene (0.36 to 3.40 mg/100 g), β-criptoxanthin (0.28 to 1.06 mg/100 g), β-carotene (0.23 to 0.50 mg/100 g), and vitamin C (25.07 to 58.59 mg/100 g) are also present.

Many scientific studies have been conducted to evaluate biological activities of various parts of papaya, including fruits, shoots, leaves, seeds, latex, and roots (Figure 1). An array of dynamic compounds with versatile action are present in various tissues of the plant, i.e., linalool in fruit pulp;^[28] dehydrocarpaine I and II, alkaloids, carpaine, and pseudocarpaine in leaves;^[29] glutaminyl cyclase in the latex; cysteine endopeptidases and class-II and III chitinase,^[30] quercetin, and kaempferol in shoots;^[31] cyanogenic compounds in roots; and benzyl glucosinolate and its degradation product benzyl iso-thiocyanate in all tissues cumulatively. All of these compounds are identified by chemical characterization of extracted metabolite.^[32]

ENZYMES: BIOACTIVE MOIETIES IN PAPAYA

Numerous biologically active moieties are present in papaya. Papaya latex is a sap that is exuded from the point of plant damage caused either mechanically or by insect herbivory^[33] and has been known to contain strong lipase activity. It is rich in cysteine endopeptidases having glycyl endopeptidase, cysteine proteinases, serine proteinase inhibitor, glutaminyl cyclase caricain, class II chitinase, papain, and chymopapain.^[34,35] Recent studies report the identification of putative homologous lipase (a hydrolase and naturally immobilized biocatalyst) that is liable for the vital lipolytic activity of papaya latex.^[36] Carica papaya lipase (CPL) has emerged as a protease having versatile biocatalytic properties;^[37] it finds abundant applications, such as fats and oils modification, facilitating a wide array of acids and alcohols as substrates for esterification and inter-esterification reactions and asymmetric resolution of different non-steroidal anti-inflammatory drugs (NSAIDs) and non-natural amino acids.

Four types of cysteine proteases are present in papaya proteases, i.e., papain (less than 10%), chymopapain A and B (26–30%), glycyl endopeptidase III and IV (23–28%), and caricain (14–26%). These form 69–89% of its total protein content.^[38] These proteases find wide application in medicine and the food industry. The method of three phase partitioning (TPP) can be effectively utilized for the extraction of proteases from papaya peels.^[39] Proteases extracted from papaya exhibit a broad specificity and thermo stability thus utilized in the meat industry for meat tenderization. Papaya proteases are of medicinal significance especially for gastroenterology, wound healing, anti-inflammatory, antitumoral, anthelmintic, neurosurgery, ophthalmology, urology, and phlebology properties.^[15,40,41] Anti-inflammatory properties of papaya proteases help to reduce pain and suffering from arthritis, edema, and osteoporosis. Papain is a non-specific thiol protease with an action similar to that of pepsin in gastric juice, an excellent aid to digestion and pepsin dilapidation.^[34,43] Endopeptidase is a minor constituent (5–8%).^[40]

NUTRITIONAL STATUS

Among fruits, papaya is greatly esteemed worldwide owing to its distinct pharmacological and functional attributes. It is an imperative fruit that reveals unique and exceptional nutritional worth.^[3,42] Hence, as a nutraceutical, its consumption may exert an anti-inflammatory response.^[43,44] In contrast to various other fruits, papaya holds a higher quantity of carotene. The comparative low calories content (32 kcal/100 g of ripe fruit) and high in nutritive value makes papaya a preferred and excellent dietary article for obese and those who are on a weight reducing regime.

Figure 1  Papaya fruit and seeds.

Figure 2  Papaya leaf.

Table 1  Area and production of papaya

Region	Area harvested (Ha)	Production (Mt)
Brazil	178,607	1,871,300
Indonesia	107,813	695,214
Australia	403	5027
India	298,984	4,713,800
Mexico	3889	616,215
Philippines	2067	165,981

Source: FAOSTAT.^[13]

Table 2  Papaya fruit nutritional value (per 100 g edible portion)

	Value—USDA		Value—USDA
Nutrient	nutrient database	Nutrient	nutrient database
Water	88.83 g	Calcium	24 mg
Energy	163 kJ/39 kcal	Magnesium	10 mg
Protein	0.61 g	Iron	0.1 mg
Fat	0.14 g	Zinc	0.07 mg
Carbohydrate (total)	9.81 g	Beta-carotene	276 μg
Carbohydrate (sugar)	5.9 g	Thiamin	0.027 mg
Dietary fiber	1.8 g	Riboflavin	0.032 mg
Cholesterol	Nil	Niacin	0.338 mg
Sodium	3 mg	Vitamin C	61.8 mg
Potassium	257 mg	Vitamin A Eq	150 μg

Source: USDA national nutrient database for reference (2006).

Table 3  General composition of FPP

Component	Level of component/100 g FPP
Moisture	8.4 g
Protein	0.3 g
Fat	Less than 0.1 g
Ash	Less than 0.1 g
Carbohydrates	91.3 g
Energy	366 kcal
Amino acids
Arginine	16 mg
Tyrosine	8 mg
Leucine	18 mg
Methionine	5 mg

Papaya is placed in the top five fruits with guava, watermelon, grapefruit, and kiwifruit, based on nutritional scores (Table 2). It is at second position owing to hydrogen peroxide and hydroxyl radical scavenging activity.^[45] Unfortunately, these nutritional aspects are exclusively ascribed to fresh fruit. Its seeds are edible with a sharp and spicy taste and are often found as a replacement for black pepper as an adulteration tactic.

Papaya delivers a broad spectrum of phytochemicals together with polysaccharides, glycosides, enzymes, flavonoids, lectins, saponins, vitamins, steroids, etc.^[46] These fundamental nutritional facts reveal that papaya contains an assay of dietary articles that may be precious for fulfilling body nutritional needs and, hence, considered beneficial for overall health.

ETHANOL PRODUCTION

There exists a huge competition involving ethanol production by fermentation process and petroleum-based products although, on escalating the value of these petrochemicals production of ethanol by process of fermentation, it has attained high interest.^[47] Owing to the fact that usage of renewable materials is proven to be particularly cheaper as these are low in cost and easily accessible. Hence, its disposal might be problematic and challenging. However, this agro-waste can be converted into alcohol, which has vast industrial applications. It has been reported that the utilization of brewer’s yeast significantly increases ethanol yield as compared to baker’s yeast. The amount of yeast prejudices ethanol production.^[48] Additionally, saccharification of waste significantly increases the reducing sugars from 7.6 to 13.6 g/100 g after 48 h, while fresh waste has the lowest.

The chemical analysis of papaya fruit extract reveals that it is a good source of energy and nutrients for the purpose of formation of cell mass with 9.8% saccharide content. Hence, by using it as a substrate the single cell protein can be produced by employing Saccharomyces cerevisiae, which is biochemically active to produce wine.^[49] The fermentation products of its seed may be beneficial for medicinal, industrial, and bio-fuel production.^[42]

MEDICINAL PROPERTIES

Papaya has been known as a food or as a quasi drug. It has wide consumption owing to its pharmacological properties^[50] and can be used as a folk remedy for various disorders. It contains different kinds of immuno-stimulating agents and antioxidants,^[51,52] Its pulp is utilized in hospitals of Africa for wounds healing as well as curing burns^[53] because management of chronic non-healing ulcers poses difficulty and many clinical problems. An amalgamation of papain-urea has been proven effective in conducting enzymatic wound debridement.^[54] According to Reed,^[55] papaya latex is very useful for curing dyspepsia and is externally applied to burns and scalds; it also cures diarrhea, bleeding haemorrhoids, and whooping cough. Papaya juice helps in alleviating infections of the colon by clearing away infection, pus, and mucus. Its ripe fruit is a carminative, diuretic, expectorant, sedative, and has preventive action against dysentery, skin diseases, psoriasis, and ringworm. Papaya also exhibits therapeutic assets against various pathological disorders. The unripe fruit is used as a remedy for ulcers and impotence;^[56] it has the ability to exhibit bacteriostatic activity against human enteric pathogens;^[57] and it aids in reducing menstrual irregularities and promotes natural menstruation flow in women. It has been recommended for controlling the most ubiquitous problem of hair dandruff. The green leaf presents an imitable source of vital and essential nutrients while the yellow one provides iron.^[58] It may have a synergistic action to reduce enlarged spleen and liver and it is used in snakebite to remove poison. Papaya fruit is thought to contain some immuno-stimulating and antioxidant agents;^[51,52] its juice is prescribed to cure gastrointestinal maladies.

DIGESTIVE HEALTH AND CELIAC DISEASE ELIMINATION

Celiac disease, a multisystem and an immune-mediated enteropathy^[59] of the small bowel, is caused by permanent sensitivity to dietary prolamins (proteic and alcohol-soluble fraction of cereals) present in gluten,^[60] in genetically susceptible individuals. It is one of the most common food intolerances found in cereal-based communities globally.^[61] The gliadin (a glycoprotein) fraction of gluten is accountable for the development of intestinal damage.^[62] Typically, in celiac disease, an immune response against cereal-derived proteins affects the absorption of nutrients by the small intestine and leads towards loss of normal mucosal architecture, and consequently, subsequent clinical and metabolic complications occur.^[63] Its ingestion provokes a persistent inflammatory response that induces flattening of intestinal villi.

Enzyme supplementation plays a vital role in the management of numerous digestive disorders, primarily with regard to protein intolerance.^[64] Recently, it is the fundamental hypothesis behind the alleviation of celiac disease symptoms by utilizing enzyme therapy.^[65] Plant-based enzymes, like papain from papaya, serve as an effective digestive aid in the breakdown of proteins. It is a complex of various enzymes that have proteolytic, amylolytic, and weak lipolytic activity. From a therapeutic point of view, papain is highly esteemed for its digestive properties, which help to digest the protein in food. Moreover, it has an action similar to that of pepsin in gastric juice. The observation that crude papain obliterates the celiac activity of gluten had earlier been made by Krainick and Mohn.^[66] The toxic exploitation of gluten is annihilated when it is digested with crude papain. Thus, it can be prescribed for dyspeptic and celiac disease patients, who cannot digest wheat protein gliadin but can tolerate it if it is treated with crude papain. The pure papain activity was rather low, in agreement with the work carried out by Messer et al.^[67] They reported that crude papain is responsible for giladin detoxification.^[68] Additionally, utilization of crude papain for hydrolyzing gluten is an appropriate and economic approach. It is observed that glutamine cyclotransferase is the factor in crude papain that abolishes celiac activity of gluten.^[65]

ANTIOXIDANT POTENTIAL

Free radicals generate in the human body and possibly their production rate increases in a majority of diseases.^[69–71] A synthetic amino-tricarboxilic acid, nitrilotriacetic acid (NTA), produces water-soluble composites in combination with iron. However, this complex is nephrotoxic and provokes renal proximal tubular damage linked with oxidative damage that ultimately leads to a high prevalence of renal cell carcinoma.^[72] Fe–NTA in company with H₂O₂ in vitro, leads increased oxidative DNA damage and in vivo.^[73] Fermented papaya preparation (FPP) (Table 3) defends super-coiled plasmid DNA against Fe–NTA and H₂O₂ persuaded single and double strand breaks. Fe–NTA induces a dose-dependent fragmentation of bovine serum albumin in vitro and diminishes cellular GSH levels in lymphocytes. Rimbach et al.^[74] conducted electron paramagnetic resonance (EPR) spin trapping studies, which indicate that antioxidant assets of FPP are associated with both hydroxyl scavenging as well as iron chelating perspectives.^[75,76] A high concentration of copper has been found in amyloid deposits in Alzheimer’s diseased brains^[77] and in the postmortem brains of Parkinson disease patients. On the other hand, FPP has also been shown to calm the apoptosis stress.^[78]

PAPAYA AND DIABETES

Globally, 90% of diabetics are suffering from type-II diabetes. This is very familiar in ethnic as well as minority groups.^[79,80] Diabetes causes oxidative stress in patients encompassing a huge risk of developing lethal diseases like neuropathy disorders, retinopathy, cardiovascular risks, and inborn malformations. Glucose oxidation results in oxidative stress that is largely augmented in diabetics. Certain other issues involved are cellular redox imbalances and attenuation of antioxidant defense bearing a small level of antioxidants in cells along with a harnessed enzymatic activity, which takes part in scavenging free radicals.^[81,82] Diabetes can be remedied by adopting certain nutritional recommendations like increased intake of fiber, weight reducing strategies,^[83] and functional food incorporation in diet plans, e.g., pycnogenols,^[84] fruits, vegetables, and legumes^[85] that have greater aptitude towards forcing the action of insulin. Recent epidemiological studies indicate that supplementation of FPP being a novel, may cater to this problem. It has been envisaged that the oral administration of FPP has the ability to produce a considerable decline in the level of plasma sugar in healthy persons as well as in patients with type-II diabetes,^[86] along with improvement of lipid profile. Many efficacy studies demonstrated that administration of diabetic mice with FPP can exhibit an elevated profusion of not only CD₆₈ but also CD₃₁ on the site of wounds, which may propose efficient monocytes recruitment as well as the superior pro-angiogenic response. It may also be visualized that FPP can alter genes controlling action and role for these proteins.^[87,88]

INFLAMMATION AND THE IMMUNE SYSTEM

Nitric oxide synthase, that is macrophage inducible, has the ability of creating nitric oxide (NO), which can take part in the immune defense system of a host in opposition to bacteria and viruses. Monocyte macrophages can be triggered by the help of a bacterial wall constituent called lipopolysaccharide (LPS) and cytokines like interferon (IFN)-inducible type of nitric oxide synthase enzyme; tumor necrosis factor (TNF) is a different central regulatory cytokines in macrophage antimicrobial action and synergy with IFN in nitric oxide (NO) amalgamation induction. FPP exerts both immunomodulatory and antioxidant action.^[89] Supplementation on FPP up-regulates the IFN-induced NO production in a precise conduct, which is dose-dependent.^[90] Ethanol-induced gastric mucosal troubles can be effectively defended by supplementation of food with FPP.^[91] It has been observed that FPP affects redox status as well as on DNA smash-up in healthy persons.^[92,93]

ANTICANCER PERSPECTIVES

Apart from its apparent nutritional portrayal, papaya may also have divergent therapeutic and chemopreventive properties owing to antioxidants or cytotoxic phytochemicals that may prove effective against some forms of cancer. Otsuki et al.^[94] demonstrated that papaya has been utilized for its indigenous activity and purported for the ostensible anti-cancer properties. Some constituents of its leaf include the fermenting agent myrosin, alkaloids, rutin, resin, tannins, carpaine, dehydrocarpaines and pseudocarpaine enzymes, ascorbic acid, and saponins that can be potentially exploited as having immunomodulatory and dramatic cancer-fighting properties against a broad spectrum of tumors; it acquires a status as a tumor-destroying agent.^[95] The presence of saponins supports the fact that papaya leaf has cytotoxic effects,^[96] while ascorbic acid leads the plant to be used in herbal medicine for treatment of prostate cancer.^[97] Moreover, its juice has been shown to have an antiproliferative effect on liver cancer cells. According to an anticipated biosynthetic trail, lycopene is the central and key compound (the most abundant carotenoids), which indicates high stimulation of its upstream steps during the stage of ripening.^[98] Likewise, Armando^[100] illustrated the protective action of papaya against rheumatoid arthritis, kidney failure, and prostate cancer. It exhibits a potent antioxidant action that has the ability to neutralize free radicals, thereby conferring defense against different kinds of cancer like breast cancer, prostate cancer, atherosclerosis, and associated coronary artery disease as well.^[99]

MALARIA AND DENGUE FEVER TREATMENT

Malaria, being one of the most prevalent disorders throughout the world, is caused by the parasites of genus plasmodium and can present itself with a myriad of distracted symptom.^[101] Recently, Saotoing et al.^[102] has reported that malaria can be effectively treated by using papaya leaves. This beneficial action is due to the presence of alkaloids in the leaves since quinine is present in alkaloids, which proves to be an anti-malarial agent.^[103]

Dengue fever, on the other hand, is the most up-and-coming viral disease of human beings, which has recently become an alarming global public health concern. It is anticipated that about 50 to 100 million cases of dengue fever occur every year that direly needs hospitalization. Dengue fever, caused by the dengue virus (belonging to the Flaviviridae family), is a mosquito-borne (Aedes aegypti) malady;^[104] it gets spread when a mosquito bites a tainted individual.^[105] Up till now, its remedy has been a serious concern to health professionals since no vaccine is present. However, Nisar et al.^[106] recently conducted a scientific study whose results reveal that dengue fever can be ameliorated by using papaya leaf extract.

Another infective agent, chikungunya vector, is also a potential risk to health so the use of papaya leaf extract in combination with spinosad (a bacterial insecticide) may have been proven to be a beneficial and eco-friendly approach for its remedy. It shows larvicidal and pupicidal action against this vector. Kalimuthu et al.^[107] explicated that leaf extract of methanol papaya has the highest larval and pupal mortality.

PAPAYA LEAF EXTRACT AGAINST VARIOUS MALADIES

Carica papaya leaves (Figure 2) are popularly used as food and have many traditional claims for herbal medicine. Phenolic compounds are important components in plant-derived foods for their beneficial effects on human health. A multitude of reports related to glucosides, allosides, phenolics, and composition of fruit and leaves of the papaya are present in the literature.^[108−113]

In addition to these, it may contain various dynamic constituents, such as rutin, methyl salicylate, pseudocarpaine, benzylglucosinolate, tocopherol, linalool, resins, dehydrocarpaines, tannins, chymopapain, papain, cyanogenic glucosides, carposide, glucosinolates, beta-carotene, cystatin, malic acid, myrosin, alkaloids, rutins, flavonoids, carpaine, and some fermenting agents. In addition, carapine is an alkaloid that has the capability to act as a heart depressant, amoebicide, and diuretic. It proves handy in the coagulation of blood, the apt functioning of heart and nervous system, and normal movement of muscles. Flavonoids are a group of widespread plant constituents. There is evidence that flavonoid-rich products contribute to the protection of skin against UV-induced damage at the molecular and cellular level. These attributes are comparable to those described for other dietary constituents, such as carotenoids and antioxidants.^[114] There regular use makes the skin supple. The role of antioxidants and phenolic compounds has been supported by epidemiological facts that these compounds show greater activity to relieve the symptoms of asthma,^[55] nervous pains, gastric troubles, amoebic dysentery and cure sores, elephantoid growth, act as vermifuge, heal wounds, and are a remedy for various disorders and infectious diseases.^[94] It also plays a vital role in prevention of various chronic diseases, including cardiovascular problems, parasitic and bacterial disorders, diabetes, and cancer.^[115,116] The composition of leaves consists of the following: calories (74 g), water (77.5 g), protein (7 g), fat (2 g), total carbohydrates (11.3), fiber (1.8 g), ash (2.2 g), calcium (344 mg), phosphorous (142 mg), iron (0.8 mg), sodium (16 mg), potassium (652 mg), β-carotene equivalent (11,565 ug), thiamine (0.09 mg), riboflavin (0.48 mg), niacin (2.1 mg), ascorbic acid (140 mg) and vitamin E (136 mg) per 100 g. The presence of iron signifies that the leaves can be used against anemia, tuberculosis, and growth disorders.^[117] As a rich source of phytochemicals, they can be used as a cleanser in herbal remedies,^[118] coupled with the presence of essential vitamins and minerals, such as Ca, Mg, Mn, Fe, Zn, K, P, and vitamins like A, C, E, and B.^108] The high concentration of Vitamins A and C is good for better eye-sight, prevention of early age blindness in children, and for those who frequently suffer from cold, cough, or flu, because intake of papaya boosts their immune system. Moreover, its regular consumption helps to relieve morning sickness, nausea, and overcomes constipation, while vitamin B₁ fights against beriberi. It is eluded that its infusion may eradicate symptoms of gonorrhea. On the other hand, freshly obtained leaf latex contains 75% water, 4.5% caoutchouc-like substances, 7% pectinous matter, 0.44% salts, 5.3% papain, 2.4% fat, 2.9% resins, and a significant amount of malic acid. The methanolic leaf extract reveals antioxidant and vasodilatatory characteristics; both of these properties are obliging in confiscating the cardiovascular risks.^[119] Moreover, its antioxidants diminish the level of lipid peroxidation. Fresh, green papaya leaf is an antiseptic, while the brown dried leaf is the best tonic as a blood purifier.^[118]

Papaya roots demonstrate abortifacient action^[120,121] and act as a generative toxin to cure piles; they also show antibacterial and antifungal activity^[122] and purgative effect.^[123] Fresh roots are administered orally with sugarcane alcohol for alleviating rheumatism. Additionally, various parts of this precious species can be effectively utilized against viral contagion. The stem and bark can fight against jaundice and exhibit anti-hemolytic activity while its flowers are febrifuge and may show pectoral properties.

BENZYL ISOTHIOCYANATE (BITC) AND CYSTEINE PROTEINASE AS ANTHELMINTICS

Okeniyi et al.^[124] reported that papaya seed extract has anti-amoebic and anthelmintic activity. Anthelmintics often affect neurotransmitter receptors that are different in the parasite and host.^[125] It has been verified through laboratory investigations that papaya seeds are effective against helminths efficiently in vitro.^[126] The anthelmintic activity is attributed to the presence of carpaine (an alkaloid) and carpasemine (later identified as benzyl thiourea by Panse and Paranjpe^[127]), and BITC.^[128,129] BITC is derived from the action of enzyme myrosinase on benzyl glucosinolate^[130] that are found in separate compartments in the seed; enzyme is brought into contact with benzyl glusosinolate. It is considered to be a principal volatile compound^[131] and is found in papaya seeds, which shows profound activity against C. elegans in vitro,^[132] and is accountable for cytotoxic effect on vascular contraction.^[133] It may inhibit movement and produce relaxation of strips of earthworm and at high doses may cause complete paralysis.^[134] Moreover, cysteine proteinase is found in papaya latex that has a potential anthelmintic property in monogastric hosts. Recently, David et al.^[139] conducted a study that provides support for the thought that cysteine proteinases may be modified to show anthelmintic properties for the remedy of lumenal stages of gastro-intestinal nematode infection in sheep.

CONCLUSION

Papaya, popularly recognized as a food article, is a terrific variety of compounds with extraordinary diverse composition. A significant number of experimentations on its biological activity and promising application of these compounds have been executed. Hence, an extensive investigation on its kinetics, pharmacodynamic properties, proper standardization as well as clinical trials is direly needed to exploit its therapeutic utility and effectiveness to fight against various maladies and conquer deficiency symptoms. It demonstrates astonishing levels of frequently cited nutritional characteristics. Clinical trials needed to have been carried out to validate the research findings and gain confidence with papain enzyme to open the way for enzyme therapy for palliative care of celiac patients. In conclusion, extracts from its different parts continue to be used in herbal medicine practice for the treatment of chronic or acute diseases, viral pathologies, and as immune modulators. Due attention should be paid to its nutraceutical, functional, and medicinal assets; its food therapy for prevention and cure of various maladies and disorders. The seeds of papaya fruits are generally discarded, however, in order to make a more efficient use of papaya, it is worth investigating the use of its seeds as a source of oil. The extraction and use of vegetable oils has for centuries played an important role in the manufacture of a large number of industrial products and food items.