Annasaheb Dange College of B. Pharmacy, Ashta, Sangli.
Carica papaya L. is a widely cultivated plant valued for its nutritional richness, phytochemical diversity, and extensive ethnomedicinal applications. This review presents current evidence on its traditional uses, chemical composition, and pharmacological activities. Different parts of the plant, including leaves, fruits, seeds, roots, latex, and flowers, encompass bioactive substances such as papain, chymopapain, carotenoids, flavonoids, phenolics, alkaloids, and benzyl isothiocyanate, which combined provide a range of medicinal benefits. Traditional medicine systems across Asia, Africa, South America, and the Pacific employ papaya for digestive disorders, infections, inflammation, wound healing, metabolic disorders, and reproductive health. Experimental studies reveal substantial antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, antibacterial, antiviral, anticancer, cardioprotective, and wound-healing activities, corroborated by both in vitro and in vivo models. Notably, papaya leaf extracts have shown promising clinical benefits in improving platelet counts in dengue-associated thrombocytopenia. Mechanistic analyses reveal modulation of oxidative stress pathways, inflammatory mediators (NF-?B, TNF-?, IL-6), metabolic regulators (IRS-1/PI3K/Akt), and apoptotic signaling in cancer models. Despite robust preclinical evidence, standardized extraction methods, dosage optimization, and large-scale clinical trials remain limited. This review focuses on the therapeutic potential of Carica papaya as a multipurpose medicinal plant and emphasizes the need for further translational research to validate its clinical efficacy and develop phytopharmaceutical applications.
Carica papaya L. also known by other names such as papaw, paw-paw, papayao, papaya, papaia, papita, lechosa and tree melon in different parts of the world is an economically and medicinally important tropical plant frequently farmed in Asia, Africa, and South American countries other warm climatic regions. Previously categorized among many scientific families, including Passifloraceae, Cucurbitaceae, Bixaceae, and Papayaceae, it is currently classified within Caricaceae, which has 35 latex-producing species distributed over four genera: Carica, Jarilla, Jacaratia, and Cyclicomorpha. [1] The papaya plant is fast-growing, reaches reproductive maturity within a year, and is capable of year-round fruit production. It is a perennial, fruit-bearing tree that produces edible fruit when ripe; however, various components of the plant, including flowers, leaves, seeds, and roots, are utilized for their significant nutritional benefits. [2]
The origins of Carica papaya traces back to southern Mexico and Costa Rica, from where it spread to all over world across tropical and subtropical regions. Its highly adaptable nature has helped its cultivation to grow in Asia, Africa, South America, and other warm climates regions.[3] owing to its fast growth, early fruiting and high yield has made it economically important [4]. India is presently the top producer of papaya, producing approximately 13.9 million tons per year while its highest consumer market is in united states. [1]
Traditionally, almost every part of the papaya plant has been used in medical applications as its high in vitamins (A, C, E), minerals such as potassium, magnesium, calcium, phosphorus bioactive substances, and secondary metabolites. Because of high antioxidant property imparted by vitamins such as vitamin A (β-carotene and β-cryptoxanthin), vitamin C (Ascorbic acid), vitamin E (Tocopherol) [5] and presence of minerals [9] (potassium, calcium, magnesium, iron, phosphorus, etc) as well as bioactive secondary metabolites such as alkaloids, flavonoids, phenolics, tannins, and saponins [2] papaya has been in use and known for their therapeutic activity in malarial infections, inflammation and immunity enhancement. [6,7,8] These nutritional values contribute in the general health, immunity, vision, antioxidant activity and metabolic health. [5]
Botanically, papaya is an herbaceous, soft-stemmed tree that grows 2–10 meters tall. The stem of papaya plant is soft wooded, with hollow green trunk while its leaves are spirally arranged that are lobed and exude latex on cut. The plant is dioecious or polygamous and can bear male, female and hermaphrodite flowers separately. The fruit is large berry, ovoid to oblong shaped. Green when unripe, can exude latex on cut but when ripe, its color changes to yellowish and the latex disappears. Inside, the seeds are in numbers, black colored and round in shape. [10]
Fig. 1 carica papaya.
Botanical Classification
Its medicinal role varies across cultures. In Ayurveda, leaves and latex are used as digestive stimulants, anthelmintics, and wound-healing agents. African communities employ papaya for malaria, jaundice, and inflammatory conditions, while Southeast Asian practices use leaf juice to manage dengue and elevate platelet counts. These long-standing uses reflect the plant’s broad therapeutic potential [11].
Phytochemicals such as carpaine, pseudocarpaine, quercetin, kaempferol, papain, chymopapain, benzyl isothiocyanate, and tannins are largely responsible for the pharmacological profile of C. papaya, contributing to antioxidant, antimicrobial, hepatoprotective, anticancer, and immunomodulatory properties [2]. It’s not only valued for its pharmacological properties but also has wide range of nutritional and industrial uses such that for Papin enzyme obtained from the carica papaya. It’s an excellent source for natural sugars, digestive enzymes and fibers making it useful in nutraceutical and food industries. Papin enzyme is one of the most known enzyme from papaya used in food, leather, pharmaceuticals, and cosmetic industries. India, Brazil, Indonesia, and Nigeria are among the top producers of papaya, whose market worth is still rising. [12,13]
Extensive in-vitro, in-vivo, and clinical investigations have revealed several biological activities of C. papaya including, antioxidant [15], anti-inflammatory [14], antibacterial [15], antimicrobial [15], antimalarial [15], antidiabetic [15], hepatoprotective [15], anticancer [15], and immunomodulatory properties [14]. These biological effects are attributed to multiple vitamins, minerals and bioactive phytoconstituents.
2. PHYTOCONSTITUENTS IN DIFFERENT PARTS OF CARICA PAPAYA
Table 1 Phytoconstituents in different parts of carica papaya [16]
|
No. |
Phytochemical Class |
Major Identified Compounds |
Source Plant Part |
|
1 |
Proteolytic Enzymes |
Papain, chymopapain (A & B), papain III & IV, peptidases A and B, glutamine cyclotransferase, lysozyme |
Latex of unripe fruit |
|
2 |
Pigments (Carotenoids) |
β-carotene, β-cryptoxanthin, violaxanthin, zeaxanthin |
Ripe fruit pulp |
|
3 |
Alkaloids & Enzymatic Components |
Carposide, myrosinase |
Roots |
|
4 |
Glucosinolate Derivatives |
Benzyl isothiocyanate, benzyl thiourea, β-sitosterol, papaya seed oil, caricin, myrosin |
Seeds |
|
5 |
Essential Minerals |
Calcium, potassium, magnesium, iron, copper, zinc |
Leaves and young shoots |
|
6 |
Volatile Monoterpenes |
Linalool, linalool oxide, 4-terpineol |
Fruits |
|
7 |
Polyphenolic Flavonoids |
Quercetin, kaempferol, myricetin |
Shoots |
|
8 |
Bioactive Alkaloids & Antioxidants |
Carpain, carpipine, pseudocarpine, carposide, choline, vitamins C and E |
Leaves and heartwood |
|
9 |
Vitamin Constituents |
Thiamine, riboflavin, niacin, ascorbic acid, α-tocopherol |
Leaves and shoots |
|
10 |
Simple Sugars |
Glucose, fructose, sucrose |
Fruits |
Fig. 2 Different structures of phytoconstituents in carica papaya
3. MAJOR BIOACTIVE CONSTITUENTS
3.1 Proteolytic enzymes:
Papain and chymopapain are abundantly present in unrip fruit, latex and leaves. Acts as a potent proteolytic enzyme exhibiting strong protein-digesting capabilities and form the biochemical basis for papaya’s traditional use in digestion, wound debridement, and anti-inflammatory applications. [10] These enzymes hydrolyze peptide bonds, facilitate enzymatic debridement, and modulate inflammatory mediators.
3.2 Carotenoids:
Papaya fruits contain abundant carotenoid pigments, including β-carotene, lycopene, lutein, and zeaxanthin, which exhibit potent antioxidant properties. These compounds play an important role in neutralizing oxidative stress, thereby contributing to cellular protection as well as supporting visual function and overall metabolic health. [10]
3.3 Phenolics & flavonoids:
Phenolic compounds and flavonoids, including quercetin, kaempferol, caffeic acid, and ferulic acid, play a major role in enhancing antioxidant activity, regulating inflammatory signaling pathways, and providing hepatoprotective effects. [17]
3.4 Isothiocyanates & benzyl glucosinolates
Papaya seeds are rich in benzyl isothiocyanate (BITC) and glucosinolates, compounds with potent antimicrobial, antiparasitic, and anticancer activity demonstrated in several experimental models [18].
4. TRADITIONAL AND ETHNOBOTANICAL USES
Carica papaya L. has long been recognized as an important medicinal plant in traditional healthcare practices of tropical and subtropical regions. Nearly all parts of the plant, including the leaves, fruits, seeds, latex, roots, and flowers, are extensively utilized in ethnomedicinal applications. Traditional knowledge from Africa, Asia, South America, and the Caribbean highlights its versatile role in healing, nutrition, and ritual practices.
4.1 Traditional Medicinal Uses:
4.1.1 Digestive aid: The ripe fruit and latex of Carica papaya are traditionally used in the management of indigestion, dyspepsia, constipation, and intestinal worm infestations, largely attributed to the activity of proteolytic enzymes such as papain and chymopapain. [19]
4.1.2 Treatment of malaria and dengue: Leaf decoctions traditionally used in India, Sri Lanka, Malaysia, and Nigeria for fever and malaria [20].
4.1.3 Anti-inflammatory and analgesic uses: Leaf paste and seed preparations are applied topically to reduce pain, swelling, and rheumatism [19]
4.1.4 Wound healing: Crushed leaves and latex are applied to wounds, burns, and ulcers to enhance tissue regeneration and prevent infection [21]
4.1.5 Women's reproductive health: Traditional use includes inducing menstruation, relieving menstrual cramps, and promoting lactation [22]
4.1.6 Diabetes management: Decoctions from leaves are used to reduce blood glucose in Indian Ayurveda and African folk medicine [23]
4.1.7 Anthelmintic use: Seeds are known for expelling intestinal worms, especially in African and Filipino traditional medicine [24]
4.1.8 Treatment of skin ailments: Latex and green fruit extracts are used for eczema, ringworm, warts, and acne [23]
4.2 Nutritional and Dietary Uses
4.2.1 Ripe fruit as a nutritive tonic: Used to treat vitamin deficiencies and improve digestion due to high levels of vitamins A, C, folate, and antioxidants [25]
4.2.2 Papaya seeds: Consumed as a natural spice and digestive stimulant; also used for detoxification in several Caribbean cultures [26]
4.2.3 Green papaya: Used in soups and salads to improve lactation and enhance immunity [27]
4.3 Regional Practices
4.3.1 Africa: Leaves used for jaundice, fever, malaria, and hypertension [28]
4.3.2 India & Ayurveda:
Latex used for digestive disorders; fruits used for wound care and menstrual issues [28]
4.3.3 South America:
Indigenous groups use latex for snakebites and seeds for parasitic infections [28]
4.3.4 Pacific Islands:
Green leaves used as postpartum tonic and to improve energy [28]
5. THERAPEUTIC USES OF CARICA PAPAYA
Carica papaya L. possesses a broad spectrum of therapeutic properties supported by in-vitro, in-vivo, and limited clinical investigations. These activities are primarily attributed to its rich phytochemical profile, including flavonoids, alkaloids, phenolic acids, isothiocyanates, and proteolytic enzymes such as papain and chymopapain.
5.1. Antioxidant Activity
Phenolics, flavonoids, and carotenoids demonstrates potent antioxidant activity of papaya leaves, seeds, and fruit extracts demonstrated by DPPH, ABTS, FRAP, and nitric oxide scavenging assays [29] Experimental animal studies further corroborate these observations, demonstrating a significant increase in endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), along with a marked reduction in lipid peroxidation levels in hepatic, pancreatic, and blood tissues. [29,30]
5.2. Anti-Inflammatory and Immunomodulatory Effects
Papaya extracts exhibit pronounced anti-inflammatory effects in macrophage, neutrophil, and lymphocyte-based experimental models. In lipopolysaccharide (LPS)-activated macrophages, leaf extracts significantly suppress the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E?, mainly by inhibiting nuclear factor-κB (NF-κB) signaling, leading to reduced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). [31,40]
Animal experiments employing carrageenan-induced paw edema, formalin-induced inflammatory models, and cotton-pellet–induced granuloma formation demonstrate a dose-dependent suppression of inflammatory responses. In addition to anti-inflammatory effects, papaya shows immunomodulatory potential, evident from enhanced phagocytic activity, improved lymphocyte proliferation, and modulation of Th1/Th2 cytokine balance. These effects are attributed to flavonoids, alkaloids, and proteolytic enzymes like papain, which synergistically regulate inflammatory signaling cascades.[29]
5.3. Antiviral and Platelet-Protective Activity:
Among the diverse pharmacological properties, the antiviral and hematopoietic activities of Carica papaya leaf extract in the management of dengue fever have attracted the greatest scientific interest. Several controlled clinical and randomized studies report that papaya leaf juice markedly increases platelet counts, shortens the duration of thrombocytopenia, and reduces hospitalization time. [31] Experimental evidence suggests multiple mechanisms:
Although direct antiviral targets remain under investigation but flavonoids, alkaloids, and unidentified bioactive peptides are suspected to contribute to these effects, with some studies suggesting modulation of immune pathways rather than direct action. Thus, papaya leaf extract represents one of the few plant-based therapies with supportive clinical evidence in dengue management.[32]
5.4. Antidiabetic Activity:
The antidiabetic potential of papaya leaf, seed, and fruit extracts has been extensively demonstrated in streptozotocin- and alloxan-induced diabetic rodent models. Oral treatment results in marked decreases in fasting blood glucose levels, enhanced glucose tolerance, recovery of pancreatic β-cell architecture, and beneficial modulation of lipid parameters. [33] At the mechanistic level, papaya phytoconstituents enhance glucose uptake by improving insulin sensitivity and regulating insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways in peripheral tissues. In addition, certain extracts inhibit α-glucosidase and α-amylase activities, thereby attenuating postprandial hyperglycemia. The antioxidant constituents protect pancreatic β-cells against oxidative stress–induced apoptosis, while phenolic compounds and flavonoids enhance mitochondrial function and glucose utilization in hepatocytes and myocytes. These findings establish C. papaya as a promising source of antidiabetic Phyto-therapeutics. [33]
5.5. Wound-Healing and Proteolytic Effects:
The wound-healing activity of Carica papaya is mainly attributed to its proteolytic enzymes -papain, chymopapain, and caricain along with its antioxidant and anti-inflammatory phytoconstituents. In experimental animal wound models, including excision, incision, and burn injuries, topical application of papaya extracts or latex results in accelerated wound contraction, increased collagen synthesis, and rapid epithelialization. Proteolytic enzymes facilitate enzymatic debridement by digesting necrotic tissue and reducing microbial load, thereby creating a conducive environment for regeneration. Clinical case series and small trials report improved healing outcomes in chronic ulcers and postoperative wounds compared with conventional dressings. Mechanistically, papaya enhances fibroblast proliferation, angiogenesis, and extracellular matrix remodeling, supporting its integration into wound-care therapeutics. [35]
5.6. Anticancer and Chemopreventive Activity:
Papaya constituents, especially benzyl isothiocyanate (BITC) found in seeds, exhibit potent anticancer effects in a range of in-vitro cell lines and animal tumor models. The extracts trigger apoptotic cell death via mitochondrial membrane depolarization, release of cytochrome-c, activation of caspase-9 and caspase-3, and elevation of intracellular reactive oxygen species (ROS) levels.[38] Additionally, benzyl isothiocyanate (BITC) inhibits cancer cell proliferation by inducing G?/M phase cell-cycle arrest and suppressing pro-survival signaling pathways, including phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and nuclear factor-κB (NF-κB). Moreover, in vivo studies have documented notable anti-angiogenic and anti-metastatic effects. Flavonoids from papaya leaves contribute to chemoprevention by reducing chronic inflammation and oxidative DNA damage. Although promising, anticancer findings are currently limited to preclinical models, and clinical validation remains necessary.[37]
5.7. Antimicrobial Activity:
Papaya leaf, seed, and fruit extracts display broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacterial strains, in addition to a range of pathogenic fungi. [38] The antimicrobial mechanism involves membrane disruption, leakage of cellular components, inhibition of microbial enzymes, and interference with quorum-sensing pathways. BITC demonstrates strong bactericidal and fungicidal activity, while phenolics and alkaloids augment these effects. Experimental studies using disc diffusion, broth dilution, and biofilm-inhibition assays consistently support the antimicrobial potential of papaya, although potency varies with extraction solvent and plant part.[39]
5.8. Cardioprotective and Vasoactive Effects
Preclinical investigations reveal cardioprotective effects of papaya extracts, including lipid-lowering, antihypertensive, and anti-atherogenic properties. In experimental hyperlipidemic animal models, papaya treatment significantly lowers total cholesterol, low-density lipoprotein (LDL), and triglyceride levels, while concurrently elevating high-density lipoprotein (HDL) concentrations. Seed extracts and BITC have shown vasodilatory effects mediated through modulation of endothelial nitric oxide production and calcium influx in vascular smooth muscle. Antioxidant actions also contribute to reduced oxidative stress in cardiac tissues. However, clinical evidence supporting cardiovascular benefits remains sparse. [40]
6. CONCLUSION
Carica papaya L. is a nutrient-dense and pharmacologically diverse plant, recognized for its extensive applications in both traditional medicine and modern scientific research. Its diverse phytoconstituents-including proteolytic enzymes (papain, chymopapain), flavonoids, phenolics, carotenoids, alkaloids, and benzyl isothiocyanate-contribute to a wide spectrum of therapeutic activities. Experimental studies consistently highlight the antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, antimicrobial, antiviral, anticancer, cardioprotective, and wound-healing activities of various Carica papaya plant parts. While traditional medicine systems have long employed papaya for managing digestive issues, infections, pain, inflammation, reproductive health, and metabolic disorders, contemporary research increasingly validates these therapeutic uses. Notably, papaya leaf extract shows promising clinical benefits in dengue-associated thrombocytopenia, highlighting its translational potential.
Despite substantial preclinical data, challenges remain in standardization of extracts, phytochemical profiling, dosage optimization, toxicity evaluation, and clinical validation. Future investigations should prioritize rigorously designed clinical trials, detailed characterization of bioactive constituents, and the development of standardized formulations to fully harness the therapeutic potential of Carica papaya. Overall, Carica papaya represents a valuable medicinal resource with significant promise for phytopharmaceutical and nutraceutical applications.
REFERENCES
Mahesh Saralaya, Vishal Dhakne, Uncovering the Therapeutic Potential of Carica papaya L.: Traditional Uses, Phytochemistry, and Pharmacological Insights, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 1, 216-225. https://doi.org/10.5281/zenodo.18137926
10.5281/zenodo.18137926
