Papaya: A Magical Tree with Medicinal, Nutritional and Pharmacological Properties

Carica papaya is a fruit tree of tropical and subtropical regions originating from America mainly central and south areas. Most of the world’s production of papaya belongs to Brazil. Majorly, Germany, Netherland and Canada import papaya species [1]. Worldwide production of papaya is shown in Figure 1. It is a multipurpose plant, and its benefits are widely ranging from nutrition to industrial uses like vitamins, minerals particularly folate compounds, proteins of both nutritional and commercial importance like papain and chymopapain, latex being used for healing wounds and other medicinal purposes and in construction too [2]. Spanish traders exported and cultivated it outside America. Mexico, and its neighboring Gulf states are the home to wild species of papaya particularly C. papaya L which is conserved only there. C. papaya L and other wild populations are dioecious whereas the cultivars are trioecious [3]. The successional subtropical and tropical forestation of wild papaya in Mesoamerica and particularly Mexico is due to the moist habitat and optimum biotic factors and most importantly large number of seeds production in the fruit. These marvelous factors led to its diversified evolution and genetic diversity around the continent [4].

Figure 1:Worldwide production of papaya (Statista, 2023).

Evolution and taxonomy

The family Caricaceae consists of 6 genera out of which Carica is the one consisting of only one species C. papaya [5]. Badillo had provided morphological, evolutionary and taxonomic studies of Caricaceae. Its species are herbs, shrubs and arborescent with complex lactifers [6] This family is widely distributed in the tropics of Africa and central and south of America. Its sister family is Moringaceae comprising thirteen tree and shrub species distributed in dry habitats of Africa, Madagascar and tropic Asia [7]. But phylogenetic dating of angiosperms and brassicales shows that during Paleocene era Caricaceae and Moringaceae slivered [8]. The molecular evolutionary studies using AFLPs, RFLPs, plastid sequences etc. could not specify representatives, so the relationship within this family is still ambiguous. The wild species are found in Mexico, Nicaragua, Belize, Guatemala and Costa Rica [9]. Vaconcellea is the largest genus of Caricaceae and is closely related to Carica along with Jarilla (3 herb species) and Jacaratia (7 species). Previously, “Carica L.” genus had been divided into two sub-genera by the taxonomists: Vaconcellea contain 1 locules in the ovary while Carica with 5 locules in the ovary [10].

Wild species and cultivars of papaya

The genera Vasconcellea of Caricaceae consists of 21 species called highland/mountain papayas i.e. wild ones. Most of these are edible and disease resistant [11]. Wild papaya species have shorter life span, are dioecious and sporadic due to natural or deliberate fragmentation of the rainforests like in Mexico and Cuba [12]. This habitat disturbance has caused loss of functional genes but not of local sex genes ratio, rapid genetic drifts [13]. Similarly, the continuous tropical habitats have higher richness in gene pool of wild populations as compared to the fragmented ones; some alleles are not passed on among the fragments due to hindered pollination and other habitat factors thus lesser gene flow and genetic structure does not diversify [14]. However; wild papayas’ resilience is due to seed dormancy thus showing low genetic variations and higher heterozygosity just like other pioneers. But heterozygosity is lower in wider areas like Venezuela, Costa Rica, Colombia and Antilles than in local populations like in Los Tuxtlas. Gene flow from undisturbed forests towards the fragments is much more than in the opposite direction due to suitable dispersal [15].

Wild papaya populations are now scarce, but still present in their originating areas where such crops are associated with cultural values and ethnicity like Mexico and Mayans from Yucatan Peninsula [16]. In these areas wild species grow spontaneously under perturbing humidity, uneven dispersal of seed and seed dormancy thereby. Wild species have shorter life span and are pioneer among natural canopies gaps of 1-5 years, man-made clearings and unplowed areas between tropics and also in secondary forests [17]. Wild species of Veracruz are placed in the same taxa as of cultivars. They survive under water stress conditions and transcriptomic, qRT PCR and RNA sequences analyses show that they can adapt to the water stress conditions by upregulating certain stress resistant genes and transcription factors, however the fruits and seeds are small and light [18]. But in such conditions cultivars’ yields are lowered due to low rate of photosynthesis, higher stomatal and other transpiration and also electrolytes osmosis is perturbed, but not in wild species. So, such evolving genes should be introduced in the cultivars for better yields [19].

The mating process of remote species causes transitional attributes among both wild and cultivated species. Selective breeding under environmental conditions different than natural ones consequently brings drastic variations in the successors. Beneficial modifications include less harsh conditions for seed germination and larger seeds (even in dark, fluctuating temperature and perturbed humidity); which get into the genomes [20]. But such cultivations require handsome gibberellin treatments and/or culturing seeds without sarcotesta showed results exactly like the cultivars of other pioneer plants like rose etc [21]. Introduction of marketable phenotypes like larger, heavier and massive fruits and seeds have compromised environmental stress dealing mechanisms particularly drought controls in these cultivars [22].

Optimum conditions for papaya plants are temperature of 21- 33 °C and cannot bear cold temperatures, humid environment, highmoderate light intensity because low light can reduce vitamin C and sugar concentrations, plenty of timely irrigation, loamed and sandy soil. Different cultivars have different fruits like green to red color flesh with rich taste and aroma and high phenol content, different shapes like long or oval [23]. All these properties also depend upon climatic and harvesting conditions. Similarly, nutritional contents like antioxidants, aromatic compounds, soluble solids, organic acids etc. also vary. For example, 2 cultivars of Bangladesh vary in fibers, carbs, vitamins and minerals [24]. Also, ripen fruits have higher content of proteins and other nutrients than the mature fruits. Cultivars are grown preferably to be hermaphrodite. They produce a variety of flowers and hence give quality fruits particularly in the lower tropics, with high photo intensity and humidity, 1200mm rain per annum and elevated temperature 21- 33 °C [25]. Using sigmoid curve models and preferably Gompertz’ equation model (based on quartiles and quadratic models) rate of growth of fruits of different cultivars can easily be analyzed [26]. Harvesting season affects the fruits ripening. For example, fruits of autumn grown crops ripen after 8 months, whereas winter grown papayas ripen during spring after 6 months and those of spring grow and ripen in 5 months; varying with the temperature of the areas. Although cultivars production depends upon climate and do vary but the small fruited and large fruiting crops need same harvesting time and other conditions [27]. Growing Degree Days GDD calculations are done to forecast the harvesting time by knowing the temperature requirements at different stages of life cycle. Different types of papaya cultivars are grown around the world including hybrids (cross pollination between wild or any cultivar naturally or artificially) with different varieties like yellow to reddish orange pulp, varying fruit size, seeds, varying colors of peel or genetically modified cultivars grown in open farms or greenhouses [28]. Worldwide cultivars include Red Lady, Golden THB, Skybury, Subang, Sekaki, Khaek Dam, Maradol, Star Papayas, Singapore Pink, Higgins, Eksotica, Honey Gold, Hybrids like Coorg Honey Dew, Washington, Ranchi, Taiwan’ hybrids, Sinta, Waimanalo, Hybrid 13 [29].

Morphology and composition

Its plants are either dioecious (individual flowers either male or female) or hermaphrodite/bisexual 20-30ft. high [30]. Some cultivars might be grown triocious meaning flowers of a single plant may contain male, female and hermaphroditic flowers. Stem with diameter of almost 1ft. are hollow, soft, fleshy, green or brown colored with blemishes and are not branched and contain fistulas at internodes [31]. Leaves are wider, lobed with 11 or 7-9 weak venations. Leaves have marginal incisions and are 2.5ft. in width. Flowers are pentamer having corolla and calyx. Male flowers are multi layered, shorter and covered with hair grown on Long Branch. Female and hermaphrodite flowers are waxy and white, grown with stem on leaf axils. Hermaphrodite buds are cylindrical, and their fruits are self-pollinating and female buds are pearshaped [32]. Corolla is tubular, anthers are adnate with 2 thecae with long connective tissue exceeding anther apex. Female flowers are larger and paucifloral. Ovaries are larger, contain 1 locule, styles are usually absent, there are five branched stigmas. Berrylike fruits, green when unripe and yellow and reddish orange when fully ripened, are found in different shapes also known as pepo like berries with hollow center containing seeds like melons. Main stem contains single axillary fruits or in clusters, each weighing 225gm to almost 1kg. Plants grow fruits after 5 to 9 months [33].

On average 100g of fresh fruit gives 179kJ of energy, 1.7g fibers, 11g carbohydrate and <1g protein or fat, 7-11g primary sugars. High concentrations of folate and minerals are present in ripened fruits. Papayas have the highest concentrations of vitamin C 35-142mg per 100g. It also contains precursors of vitamin A carotenoids. Inorganic nutrients include Potassium 3-7%, Magnesium 6-8%, Copper 9% [34].

Fruit contains variety of organic and inorganic components like citric acids and molic acid, dietary fibers, carbs, protein, salts like P, Ca and Fe; vitamin C, cofactors like thiamine, niacin, and caroxene, volatile compounds like linalol, 2,6-dimethyl-3,6expoxy- 7octen-2-ol, benzylisothiocynate and alkaloids like α-carpaine, 2-phenylethyl-β-D-glucoside, benzyl-β-d glucoside, 4-hydroxylphenyl- 2ethyl-B-D-glucoside and four isomers of benzyl-β-D malonate glucosides [35]. Juice contains lipids like stearic acid, myristic acid, palmitic acid, linolenic acid etc. Seeds contain fatty acids, crude raw material like proteins, fibers, papaya oil, carpaine, caricin, glucotropacolin, hentriacontane, benzylglucosinolate, benzylisothiocynate, benzylthiourea, β-sistosterol, and an enzyme nyrosin [36]. Roots contain an enzyme myrosin and arposide. Leaves contain alkaloids like carpain, dehydrocarpaine I and II, pseudocarpain choline and carposide, vitamin C and E. Barks contain glucose, fructose, sucrose, galactose, β-sitosterol and xylitol. Latex obtained from barks contains proteolytic enzymes like glutamine cyclotransferase, peptidases and lysozymes and most importantly papain and chemopapain [37].

Nutritional attributes

Papaya is a cheap and healthy fruit with high nutrient content as can be inferred from its chemical composition. It’s low in calories 32Kcal per 100g is a favorable diet for obesity problems. Low carotene content prevents free radical formation [38]. However dark colored pulp contains high content of beta carotene; a precursor of vitamin A; hence improves eyesight. It’s rich in proteolytic enzymes which improve digestion in any media particularly papain (vegetable pepsin), which also helps treat ulcers and bacterial infections particularly gram negative [39]. Even crude papain can tenderize meat. Celiac patients cannot digest wheat but with papain they can eat wheat. Fermented papaya products, if taken in prescribed amount, are good nutraceutical antioxidants. Papain linked lipase, a natural biocatalyst, can serve different purposes [40]. Papaya helps absorption of iron from rice when eaten with rice. Seeds have a sharp pungent taste like black peppers and can be used as a healthy spice. Its leaves are also used as spinach in some parts of Asia [41].

Pharmacological attributes

The seed extracted benzyl isothiocyanate is an antibacterial and fungicide. Its vitamins, enzymes and other components show marvelous antioxidant and anti-inflammatory effects [42]. Papaya leaves extracts have scientifically proven diverse medicinal and therapeutic value in different fevers, jaundice etc.so have seeds, fruit pulp, latex, flowers and barks in different criteria like anticancer, in pregnancy, anti-infection activities [43]. Medicinal and therapeutic uses of different parts of papaya are given below:
Leaf extracts: Papaya leaf components contain flavonoids, tannins, saponins, alkaloids, phenolics and steroids in minute percentages [44]. They interact with different metabolic targets like with DNA topoisomerase I/II, disrupting the pathogenic signaling pathway, inhibiting the expression of Bcl-2 and Bcl-XL genes or enhancing the expression of Bax, cleaved caspase 3 and P53 genes to produce anticancer effect [45]. They can increase TNF α, cytokines like IFN-γ, IL-6, IL-12p40, IL-12p70, and can decrease or modulate the secretion of pro-inflammatory cytokines and chemokines like: IL-1β, IL-6, IL-1α, IL-2, IL-4, IL-8, and CCL2, CCL7, CCL8. In dengue, papaya leaf extract juice has been successful by activating PTAFR and ALOX 12 gene. Frozen leaves extracts have been successfully tried on lab mice and rats against dengue and diabetes [46].

Due to a number of raising concern of toxicity of synthetic anticancer drugs, researchers are now working on nutraceuticalphytochemical anticancer therapies with least adversities, papaya grinded extracts particularly leave aqueous extracts are one such best example [47]. This extraction method shows cytotoxicity against benign, malignant and normal cells of cancer. Blood, pulmonary, renal, pancreatic and stomach cancer patients of varying severity survived after intake of aqueous extracts [48]. Crude extracts change their biochemical properties during digestion a little as compared to the in-vitro digested extract. They have stopped proliferation of prostate cancer cells by apoptosis. Their antitumor activity is owed to activation of mitochondrial pathway via activation of caspase three-sevenths and p53 and also in other cancers like breast cancer. As a rough estimate, papaya leaf extracts can stop metastasis by reduction in ECM around malignant cells [49].

Papaya leaf extracts have been shown to protect against dengue, cancers, cardiac disease, healing, allergic disorders like asthma etc. due to immune modulation as described above. For example, in dengue, papaya can control bleeding and can normalize platelets count and has been clinically shown [50]. Different minute concentrations of crude extracts have been shown to inhibit the sickle cells, but processed leaves extract with HbSSsodium metabisulphite gave the highest results. Osmotic control and hemoglobin polymerization is also decreased in RBC [51]. The benefits of papaya leaf extract are shown in Figure 2 [52].

Figure 2:Benefits of papaya leaf extract [52].

Seeds extracts: Papaya seeds treated under different conditions have shown like aqueous or alcoholic extracts, seed oils have proven antioxidant, immune-modulatory effect [53]. Likewise, mixture of dried seeds and honey has an excellent relieving effect against intestinal helminths. The alkaloid Benzyl isothiocyanate BITC is the major anti-helminthic shown in different studies e.g. against C. elegans, ascaris infections [54]. Seeds extracted in ethanol can relieve smooth muscles’ contractility. Their aqueous solutions have shown antioxidant activity against hydrogen peroxide in skin fibroblasts and can also scavenge other free radicals. They treated with H2O2 can do so more efficiently than ascorbic acid as it stops catalase activity C thus cytochrome C is so not released thus maintaining the mitochondrial membrane potential [55]. The benefits of papaya seed extract are shown in Figure 3 [56].

Figure 3:Benefits of papaya leaf extract [52].

Papaya is one of the most grown plants worldwide. It has a variety of qualities ranging from economic to nutritional. There are numberless studies done on traits of natural and cultivated types of papaya and on their botanical, economical and nutritional qualities. It suggests a need of research over its several aspects for production and farming of papaya in Pakistan since we too have a favorable climate and soil conditions that can bear valuable papaya cultivars. Genetic comparative studies show that cross cohort studies to be conducted for attaining hybrids of having best traits of both wild species and cultivars. Genetic engineering-based research in this regard to have optimum yields should be increased. Papaya has innumerable nutritional and medicinal benefits. In recent years, a lot of studies have been performed on papaya leaves extract particularly as anticancer therapies and as adjuvants. Similarly, papaya seeds and latex have equal benefits and studies are being conducted day by day. No doubt papaya is a magical plant and its increased production round the year is needed for welfare of humankind.