Current Research in Biotechnology 2 (2020) 145–160

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Current Research in Biotechnology

journal homepage: www.elsevier.com/locate/crbiot

Phytochemistry, pharmacological activities, nanoparticle fabrication,

commercial products and waste utilization of Carica papaya L.: A
comprehensive review
Ashutosh Sharma a, Archana Bachheti b, Priyanka Sharma c, Rakesh Kumar Bachheti d, Azamal Husen e,⇑
a
Department of Applied Science, Doon Institute of Engineering and Technology, Rishikesh, Uttarakhand, India
b
Department of Environment Science, Graphic Era University, Dehradun 248002, Uttarakhand, India
c
Department of Biology, The Indian Cambridge School, Dehradun 248001, Uttarakhand, India
d
Department of Industrial Chemistry, College of Applied Sciences, Addis Ababa Science and Technology University, P.O. Box: 16417, Addis Ababa, Ethiopia
e
Wolaita Sodo University, P.O. Box: 138, Wolaita, Ethiopia

A R T I C L E I N F O A B S T R A C T

Keywords: Fruits and vegetables are an important part of a healthy diet. In this regard, Carica papaya (papaya) is one of
Fruit them, a native to Mexico and northern South America, now naturalized in many parts of the world including
Leaves tropical and subtropical regions. The papaya fruit pulp is rich in minerals and many vitamins, while seed con-
Phytochemical constituents tains glucosinolates, tocopherols, carotenoids, and benzyl isothiocyanate. Papaya is known for numerous activ-
Pharmacological activities
ities such as antioxidant, antibacterial, anticancer activity, anti‐fertility agent, anti‐inflammatory, antiulcer,
Nanomaterial synthesis
Applications
antidiabetic, hepatoprotective, and many more due to the presence of phenolics, flavonoids, and alkaloids
as the key phytochemicals. Many commercial products obtained from different plant parts are available in
the market and are being utilized for various purposes. More specifically, papaya fruit is used to produce a large
number of processed foods such as jam, jelly, pickle, candied fruit, puree, concentrate, and canned slices/
chunks. Fruit peels find its application in cosmetics, in wastewater treatment, as animal feed, and as a binder
in ceramics. Papaya leaf, bark, root, and seeds have also shown the insecticidal and repellent activities. More
interestingly, in the recent past, papaya and different parts are used for nanoparticle synthesis which has shown
numerous applications. This review mainly focuses on the various phytochemicals present in different parts of
plant C. papaya, their pharmacological activities, and several other applications. For writing this review paper,
a literature survey was carried out via classic books of medicinal and fruit plants. Online scientific databases,
for instance, PubMed, Scopus, Sci Finder, Science Direct, the Web of Science, Wiley Online, Google Scholar,
ResearchGate, and other search engines were explored up to October 2020 to detect valid reports, studies,
and investigations. All literature on the proposed topics were analyzed and summarized in this review paper.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
2. Method for literature search. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
3. Morphological features of papaya . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
3.1. Geographical distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
4. Chemical composition and isolated compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
5. Pharmacological activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
5.1. Antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
5.2. Insecticidal and repellent responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
5.3. Antibacterial activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
5.4. Antidiarrheal responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
5.5. Wound-healing activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

⇑ Corresponding author.
E-mail address: [email protected] (A. Husen).

https://doi.org/10.1016/j.crbiot.2020.11.001
Received 20 September 2020; Revised 30 October 2020; Accepted 3 November 2020
Available online xxxx
2590-2628/© 2020 The Authors. Published by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
A. Sharma et al. Current Research in Biotechnology 2 (2020) 145–160

5.6. Anticancer activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152

5.7. Anti-malarial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
5.8. Anti-dengue activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
5.9. Anti-inflammatory and immunomodulatory responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
6. Nanoparticle fabrication from papaya and their applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
7. Use of papaya in processed food and beverages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
8. Use of papaya waste . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
9. Commercial products from papaya . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
10. Miscellaneous activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
11. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Declaration of Competing Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

1. Introduction tenderizing meat and pharmaceuticals. The raw fruit of papaya has
laxative property and along with the fruit, the leaves are also useful
Carica papaya L. (papaya) from family Caricaceae, a native to Mex- in pyrexia, diabetes, syphilis, and in the healing of wounds
ico and northern South America, is now naturalized in many parts of (Sudhakar and Theivanai Vidhya, 2014). Leaf and fruit extract of
the world including tropical and subtropical regions. According to papaya exhibit antimicrobial and antioxidant activity due to the pres-
the FAO (2020), global production of papaya is estimated to rise by ence of phenols, vitamins, and enzymes (Addai et al., 2013; Maisarah
2.1 percent each year, up to 16.6 million tonnes in 2029 (FAO, et al., 2013; Zuhair et al., 2013).
2020). India is the largest producer of papaya and its share of world Fruit and leaf extract papaya was reported to cure dengue fever and
production is expected to rise from 59% to 61% in 2029. In the year help to increase blood pallets count (Ahmad et al., 2011;
2017 and 2018, the export of C. papaya decreases due to bad Dharmarathna et al., 2013). The reported remedial properties of vari-
weather‐related issues but the global export of C. papaya is increased ous parts of C. papaya include anti‐hypertensive, antibacterial, diure-
by 8 percent in 2019, to approximately 310 000 tonnes. Mexico is tic, antifertility, antifungal, and antitumor effect (Vij and Pasha,
the largest exporter of papaya and it is estimated that during 2019, 2015; Singh et al., 2020a, 2020b, 2020c). Papaya plants have also
its export is increased by 7 percent, thus they share in the global trade shown a beneficial effect on wound healing, immunomodulation;
of over 50 percent (Fig. 1). It is a semi‐herbaceous tree‐like plant that hypolipidemic and hypoglycemic conditions (Nayak et al., 2007;
grows up to 8 feet with stem, hollow, and cylindrical. Papaya is known Juárez-Rojop et al., 2012; Pandey et al., 2016; Santana et al., 2019).
by various names in many parts of the world and different languages. Further, some recent reports have revealed the use of C. papaya in dif-
Papaya is a source of vitamins A, C, and E; minerals (viz., potassium, ferent discipline, for instance, corrosion inhibitor (Tan et al., 2020),
magnesium, etc.), carotenoids; phenolic compounds, fiber, and folate. multi dye degradation (Jain et al., 2020; Bhuiyan et al., 2020), biodie-
C. papaya is used traditionally by many countries due to its nutritional sel/diesel blends (Devarajan et al., 2020 Minakshi et al., 2020) and
and health benefits. Reports were available which showed that C. nanoparticle fabrication (Jain et al., 2020; Bhuiyan et al. 2020;
papaya is mixed with other herbs to treat diseases (Anuar et al., Singh et al., 2020a, 2020b, 2020c) and so on. The scattered reports
2008). In Nigeria, it is used to treatment of diabetes by traditional doc- (phytochemical/phytochemistry, pharmacological activities, nanopar-
tors (Gbolade, 2009), in malaria and fungal infections (Okpe et al., ticle fabrication from different plant parts, waste utilization, and some
2016), as an antimalarial herbal mixture with other herbs in Cameroon other miscellaneous uses of C. papaya) are collected and presented as
(Tarkang et al., 2013), decoctions of leaf reported as anticancer reme- inclusive information in this communication. Thus, taken together, we
dies by aboriginal Australians (Nguyen et al., 2016). herein review those findings, which highlighted the isolated phyto-
Papaya also reported being a rich source of the digestive enzyme chemical compounds present in C. papaya plants, their pharmacologi-
papain, which has applications in cosmetics, brewing industries, in cal activities, and various applications. Also, there is a focus on the

Fig. 1. Papaya development of volumes from the leading exporters 2009 to 2019 [adopted from FAO, 2020]

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utilization of papaya fruit for processed food; and its wastes for pro- are racemose type. The fruit is 5–30 cm long and yellowish‐orange
ducing various value‐added products. in colour. Fruit contains several black seeds and pulp is sweet
(Nadkarni, 1954).
2. Method for literature search

Online scientific databases, for instance, PubMed, Scopus, Sci Fin- 3.1. Geographical distribution
der, Science Direct, the Web of Science, Wiley Online, Google Scholar,
ResearchGate, and other search engines were explored up to October Papaya exotic ranges are United States of America, Mexico, Costa
2020 to detect the valid reports, studies, and investigations. All litera- Rica; while natives ranges are Grenada, Colombia, Democratic Repub-
ture on the proposed topics such as phytochemical constituents from lic of Congo, Nicaragua, Jamaica, Australia, Bahamas, Malaysia, Eri-
Carica papaya, pharmacological activities of Carica papaya, waste trea, Fiji, Ecuador, Guadeloupe, Netherlands Antilles, Dominica,
application of Carica papaya, nanomaterial synthesis and or fabrication Barbados, Brazil, Kenya, Indonesia, Martinique, India, Montserrat, Sin-
from Carica papaya and their application, Carica papaya uses, Carica gapore, Dominican Republic, Cambodia, Cameroon, Philippines, Peru,
papaya and therapeutic potentials, Carica papaya and future research, Puerto Rico, Antigua and Barbuda, New Zealand, Cuba, Sri Lanka,
etc. were analyzed and summarized in this review paper. Solomon Islands, Uganda, Chile, Haiti, Laos, St Lucia, Nigeria, Papua
New Guinea, Myanmar, Tonga, Samoa, Sudan, South Africa, Thailand,

3. Morphological features of papaya

Papaya is an herb in nature but its structure is not similar to herb

and looks somewhat like a tree. C. papaya is commonly called Papaya
(Yogiraj et al., 2014). Other names of this plant are Papye, Pawpaw,
Lapaya, Tapayas, Kapaya (Bhattachrjee, 2001). Papaya is erect, big
herbaceous plants look like trees but not woody. Leaves are of com- Neochlorogenic acid Apigenin

pound type. Leaves are very large and the morphology of leaves shows
palm shape and the average size of the leaf is 50–70 cm in diameter.
Papaya flowers are generally dioecious. The fruit that develops varies
in shape depending on the flower type. Male flowers are straw‐colored.
Corolla tube is cylindrical which is about 2 cm long. Female flowers

Kaempferol Papain

Quercetin-3-O-glucopyranoside Carpaine p-Hydroxybenzoic acid Salicylic acid Hyperoside

Quercetin Caffeic acid

Dehydrocarpaine I Dehydrocarpaine II

Benzyl isothiocyanate Oleic acid

Gentisyl alcohol Trigalloyl glucose

Kaempferol 3-O- rutinoside Quercetin-3-O-rutinoside

5, 7 Dimethoxycoumarin Protocatechuic acid Kaemferol hexoside Chrysin

Fig. 2. Phytochemicals present in different parts of Carica papaya. Fig. 2 (continued)

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extract of leaves showed the presence of different components such as

anthraquinone, glycoside, tannin, saponin, flavonoid, steroid and
resin. Chromatography (column chromatography) and spectroscopy
Beta- carotene Ferulic acid methods (NMR, IR and mass spectrometry) were used for the isola-
tion and characterization of carpaine from the leave. The amount
of carpaine in the leaves was 0.93 g/kg determined by HPLC‐ UV
method (Wang et al., 2015). According to a research study by El‐
Mesallamy et al. (2015), it was found that the methanolic leaves
extract of papaya contains phenolic compounds. Chromatography,
Lycopene p – Coumaric acid
spectroscopy analysis and mass spectrometry were used to establish
the structure of isolated phenolic compounds. The major isolated
compounds were protocatechuic acid, chlorogenic acid, caffeic acid,
quercetin, kaempferol, quercetin 3‐O‐α‐1C4‐ rhamnopyranoside,
quercetin ‐3‐O‐glucopyranuroside, quercetin‐3‐O‐rutinoside, p‐
Vanillic acid Beta- cryptoxanthin coumaric acid (Fig. 2). Quantitative HPTLC assessment of leaves
H aqueous extract showed the presence of compounds kaempferol,
N
H H H O
H trans‐ferulic acid, caffeic acid, and myricetin. These were recognized
O H by using Ultra‐performance liquid chromatography ‐quadruple
orthogonal acceleration time of flight tandem mass spectrometer
H H H H

Chlorogenic acid 1,2,3,4-tetrahydropyridin-3-yl-octanoate (UPLC‐qTOF/MS) technique which was twenty‐four in number

(Anjum et al., 2017). One research investigation concluded that
leaves contains various phytochemicals such as carpaine, kaempferol
3‐(2G‐glucosylrutinoside), kaempferol 3‐(2″‐rhamnosylgalactoside),
7‐rhamnoside, kaempferol 3‐rhamnosyl‐(1‐>2)‐galactoside‐7‐rhamno
Isochlorogenic acid Sinapic acid Malic acid side, luteolin 7‐galactosyl‐(1‐>6)‐galactoside, orientin 7‐O‐
rhamnoside, 11‐hydroperoxy‐12,13‐epoxy‐9‐octadecenoic acid, pal-
mitic amide, and 2‐hexaprenyl‐6‐methoxyphenol (Soib et al., 2020).
Benzyl glucosinolate and benzyl isothiocyanate have been found in
the seeds, pulp, and pericarp of the papaya (Nakamura et al., 2007;
Cinnamic acid Coumaric acid Rossetto et al., 2008). Ghosh et al. (2017) isolated oleic acid from
the seed. The structure of the isolated compound was examined by
Fig. 2 (continued) Fourier‐transform infrared spectroscopy (FTIR), Proton nuclear mag-
netic resonance (1HNMR) and Carbon‐13 (C13) nuclear magnetic res-
onance (13CNMR) spectroscopy along with mass spectrometry. The
Trinidad and Tobago, St Kitts and Nevis, St Vincent and the Grenadi-
Antifertility compound was isolated from ethyl acetate extract of seeds
nes, Tanzania, Venezuela, Vietnam, Virgin Islands (US) and Zanzibar
of C. papaya and the structure of this isolated compound was eluci-
(Orwa et al., 2009).
dated by spectroscopic methods The isolated compound was identified
as 1,2,3,4‐tetrahydropyridin‐3‐yl‐octanoate (Julaeha et al., 2015).
4. Chemical composition and isolated compounds From the ethanolic extracts of the seeds, two new compounds named
as glyceryl‐1‐(20 ,30 ,40 ‐trihydroxybenzoyl)‐2,3‐dioleate(papayaglycer
Papaya leaves contain tannin, saponin, alkaloid, flavonoid, and gly- ide) and 2,3,4‐trihydroxytoluene (caricaphenyltriol)were isolated.
coside; while shoots contain various minerals like Ca, Fe, Mg, K, Zn, The structure was examined by chemical and spectroscopic methods
Mn etc. Enzymes are present in the unripe fruit such as papain and (Singh and Ali, 2011). GC‐MS analysis of seed extract showed the pres-
chymopapain. Fruit also contains carotenoids β carotene and crytoxan- ence of fatty acid, amide, nitriles, sterol, fatty aldehydes, and organic
thin. The chemical composition of the root showed the presence of acids (Sani et al., 2020). One of the compounds termed as dilactone
benzyl isothiocyanate, glucosinolatescarposide. Papaya oil is found alkaloid, Carpaine was also isolated from the leaves (Teng et al.,
in seeds and also contains flavonoids, kaemferol, myricetin, and fruit 2019).
contains Linalool,4‐terpinol, monoterpenoids (Adachukwu et al., Gas chromatography‐mass spectrometry (GC–MS) technique was
2013). Enzymes were found in latex as well as in other parts of plants, used to recognize the phyto‐components present in unripe fruit aque-
for example, papain, chymopapain, caricain, and protease omega ous extract and showed the presence of fifteen phytochemical com-
(Azarkan et al., 2003; Brocklehurst et al., 1985; Dubois et al., 1988, pounds. The major phytochemical compounds were hexadecenoic
1989). Latex of C. papaya was also reported to have enzymes like cys- acid, Z‐11, methyl ester, and octadecanoic acid (Ezekwe and
teine endopeptidases, chitinase, and glutaminyl cyclase (Azarkan Chikezie, 2017). The GC–MS technique was used to identify phyto-
et al., 2006). components present in unripe fruit aqueous extract which showed that
Seven flavonoids were obtained from the papaya leaves, named as fifteen phytochemical components were present. The major phyto-
quercetin, kaempferolkaempferol 3‐rutinoside, quercetin3‐(2G‐rham chemical compounds were hexadecenoic acid, Z‐11, methyl ester,
nosylrutinoside), quercetin 3‐rutinoside, kaempferol 3‐(2G‐ and octadecanoic acid. Minor phytochemical compounds present in
rhamnosylrutinoside), myricetin 3‐rhamnoside (Nugroho et al., the unripe fruit aqueous extract of this plant was within the range of
2017) (Fig. 2). (Chandrika et al., 2003) reported that the fruit con- 0.78–5.38% (Ezekwe and Chikezie, 2017). Pino and Queris (2012)
tains phytochemicals flavonoids‐kaempferol, myricetin, quercetin used gas chromatography‐mass spectrometry to isolate the volatile
and carotenoids – lycopene, zeaxanthin, cryptoxanthin, β‐carotene compounds of papaya wine by continuous solvent extraction. The
and violaxanthin. (Canini et al., 2007) reported that the presence study showed that papaya wine contains two aldehydes, three ketones,
of the various phenolic compound in the leaves for example kaemp- five terpenes, five lactones, seven phenols, seven sulphur compounds,
ferol, protocatechuic acid, quercetin, 5,7‐dimethoxy coumarin, caffeic nine acids, twenty‐two alcohols, fifty‐three esters. Isolated compounds
acid, p‐coumaric acid, and chlorogenic acid in plant leaves. Another from different parts of C. papaya obtained by various techniques are
study by (Musa, 2015) reported that n‐hexane extract and methanolic summarized in Table 1.

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Table 1
Isolated compounds from Carica papaya.

Isolated compounds/phytoconstituents Parts Methods used Reference

investigated

Kaempferol 3‐O ‐α ‐L ‐arabinopyranoside, kaempferol 3‐O ‐α ‐L ‐rhamnopyranoside, kaempferol 3‐ Male flowers Extraction, chromatography, (Van et al., 2020)
O ‐β ‐D ‐glucopyranoside, myricitrin, quercetin and quercetin 3‐O ‐β ‐D ‐galactopyranoside of C. papaya spectroscopy, mass spectrometry
Myricetin, caffeic acid,trans-ferulic acid, and kaempferol Leaves Ultra-performance liquid (Anjum et al., 2017)
chromatography–mass
spectrometry
Carpaine Leaves Column chromatography, FTIR, (Wang et al., 2015)
MS, NMR spectroscopy
Lycopene, β-carotene and β -cryptoxanthin Fruit HPLC analysis (Sangsoy et al.,
2017)
Quercetin 3-O-[a-L-rhamnopyranosyl (1/2)] [a-L-rhamnopyranosyl (1/6)]-β-D-glucopyranoside, Leaves Chromatographic and (Nugroho et al.,
kaempferol 3-O-[a-L-rhamnopyranosyl (1/2)][a-L-rhamnopyranosyl (1/6)]-β-D- spectroscopic techniques 2017)
glucopyranoside, Quercetin 3-O-a-L-rhamnopyranosyl-(1/6)- β-D-glucopyranoside, Myricetin 3-
O-a-L-rhamnopyranosyl, kaempferol 3-O-a-L-rhamnopyranosyl-(1/6)-β-D-glucopyranoside,
quercetin and kaempferol
p-hydroxybenzoic acid, salicylic acid, hyperoxide, genteel alcohol, triallyl glucose and Seeds LC-MS analysis (Singh et al., 2020a,
kaemferolhexoside 2020b, 2020c)
Carpaine, kaempferol 3-(2G-glucosylrutinoside), kaempferol 3-(2″-rhamnosylgalactoside), 7- Leaves HPLC-MS/MS-QTOF analysis (Soib et al., 2020)
rhamnoside, kaempferol 3-rhamnosyl-(1->2)-galactoside-7-rhamnoside, luteolin 7-galactosyl-
(1->6)-galactoside, orientin 7-O-rhamnoside, 11-hydroperoxy-12,13-epoxy-9-octadecenoic
acid, palmitic amide and 2-hexaprenyl-6-methoxyphenol
Carpaine Leaves Bioassay-guided fractionation and (Teng et al., 2019)
LC-MS
Octadecanoic acid, hexadecenoic acid, Z-11 and hexadecanoic acid and methyl ester Unripe fruit GC–MS analysis (Ezekwe and
Chikezie, 2017)
1
Oleic acid Seeds GC–MS analysis, FTIR, HNMR and (Ghosh et al., 2017)
13
C NMR
Stigmast‐4‐ene‐3‐one, β‐sitosterol3‐O‐β‐D‐glucopyranoside,3‐O‐(6‐O‐tetradecanoyl‐β‐D‐ Flowers and Extraction, chromatography and (Nga et al., 2020)
glucopyranosyl)‐β‐sitosterol, benzyl β‐D‐glucopyranoside, uracil and palmitic acid petioles spectroscopic method
Carpaine Leaves HPTLC analysis (Haldar et al., 2020)
Ferulic acid, caffeic acid, p-coumaric acid, kaempferol-3-glucoside, p-hydroxybenzoic acid, Seeds LC–ESI–DAD–MS/MS analysis (Kadiri et al., 2017)
quercetin-3-galactoside
Oleic acid, n-hexadecanoic acid, octadecanoic acid, 11-octadecenoic acid, methyl ester, Seeds GCMS analysis (Agada et al., 2020)
pentadecanoic acid, 14- methyl-, methyl ester
Prunasin and sambunigrin Leaf and stem Extraction, chromatography, Mass (Seigler et al.,
spectrometry and 1H NMR 2002)
β-sitosterol and stigmasterol aerial parts Extraction, chromatography, 1H (Khaled and Gerda,
NMR 2013)
2-methoxy-4-vinylphenol Leaf GCMS analysis (Farida and
Iswahyuni, 2018)
Equisetin, 50 -epiequisetin and tenuazonic acid Leaves HPLC (Eze et al., 2019)
Quercetin and β-sitosterol Fruit HPLC (Oloyede et al.,
2016)
Carpaine Leaves HPLC (Vien and Loc,
2017)
Hexahydro-1-aH-naphtho[1,8a-b]oxiren-2(3H)-one, 3,7- dimethyloct-7-en-1-ol, 3-methyl-4- Leaves GCMS (Igwe, 2015)
(phenylthio)-2-enyl-2,5-dihydrothiophene-1,1-dioxide, cyclopentaneundecanoic acid methyl
ester, 3,7,11,15-tetramethyl-2- hexadecen-1-ol and 9-octadecenamide

5. Pharmacological activities (2016) reported that the ethyl acetate extract of unripe fruit containing
β ‐ sitosterol and quercetin are responsible for the antioxidant proper-
C. papaya is tremendously efficient in different types of ailment ties. Silver nanoparticles (Ag‐NPs) synthesized from C. papaya peel
cure due to availability of wide varieties of phytoconstituents in almost extract (CPPE), and was tested for their antioxidant activity. The result
all parts of plant. revealed that 56% average inhibition for synthesized Ag‐NPs and 38%
for CPPE at different concentrations and the activity is concentrations
5.1. Antioxidant activity dependent on Ag‐NPs (Kokila et al., 2016). One recent research inves-
tigation reported that the antioxidant activity of methanolic extract of
Free radical causes many chronic health problems. Antioxidants seeds was determined by DPPH free radical scavenging activity (Singh
can help us by preventing the formation of free radicals. Research is et al., 2020a, 2020b, 2020c). In another study, papaya seed extracts
going on to find new sources of antioxidants of natural origin which were used to examine the antioxidant activity and results revealed that
are safe and economically viable. According to a study hexane fraction the highest DPPH free radical scavenging ability was found in hexane
of C. papaya male flower shows a good antioxidant activity (IC50 = extract and the least activity in the aqueous extract (Agada et al.,
100.81 ± 1.180). Low IC50 value reflects a high antioxidant activity 2020). Nisa et al. (2019) study the antioxidant activity of papaya
of fractions (Chakraborty et al., 2015; Koleva et al., 2002). The antiox- leaves with different varieties, maturity, and solvent. The solvents
idant capacity of fruit extract in the ripening stage was determined by used for extraction were water, methanol, and ethanol 70%. Results
different methods (Ferric reducing antioxidant power, 2,2‐diphenyl‐1‐ showed that mature leaves extracted with water exhibited the highest
picrylhydrazyl (DPPH) and 2,2‐azinobis‐3‐ethylbenzothiazoline‐6‐sul antioxidant activity higher than others. According to Shen et al.
fonic acid) and result showed that the antioxidant activity papaya fruit (2018), the enzyme PaMsrB1 (Plant methionine sulfoxide reductase
increased in the ripening stage (Zuhair et al., 2013). Oloyede et al. B1) from papaya was examined with Escherichia coli which contain

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Table 2
Antioxidant activities of Carica papaya.

Parts used Type of extract Method used Responsible phytochemicals Reference

G
Leaf MeOH Peroxynitrite scavenging assay Kaempferol 3-(2 rhamnosylrutinoside) (Nugroho et al.,
2017)
Stem Papayasayanam Hydrogen peroxide scavenging – (Sivasankari et al.,
activity, reducing power assay 2019)
Leaves Ethanol, Methanol and water DPPH, FRAP Flavonoids (Nisa et al., 2019)
Seeds Hexane, chloroform, diethyl DPPH p-hydroxybenzoic acid, salicylic acid, hyperoside, gentisyl alcohol, (Singh et al.,
ether, and methanol trigalloyl glucose, kaemferol hexoside 2020a, 2020b,
2020c)
Leaves Methanol DPPH Carpaine, kaempferol 3-(2G-glucosylrutinoside), kaempferol 3-(2″- (Soib et al., 2020)
rhamnosylgalactoside), 7-rhamnoside, kaempferol 3-rhamnosyl-(1-
>2)-galactoside-7-rhamnoside, luteolin 7-galactosyl-(1->6)-
galactoside, orientin 7-O-rhamnoside, 11-hydroperoxy-12,13-epoxy-9-
octadecenoic acid, palmitic amide, and 2-hexaprenyl-6-methoxyphenol
Leaves Methanol DPPH – (Mohansrinivasan
et al., 2017)
Fruit Methanol DPPH – (Setiadi and
Anindia, 2018)
Leaves, n-hexane, dichloromethane, DPPH Phenolics and flavonoids (Asghar et al.,
bark, ethyl acetate, ethanol, methanol, 2016)
roots n-butanol and water
and
pulp
Seeds Petroleum ether, ethanol and DPPH, FRAP, ABTS•+, Metal Phenolics and flavonoids (Sofi et al., 2016)
aqueous chelating activity, Lipid
peroxidation inhibition
Seeds Methanol DPPH, FRAP, TEAC Carotenoids and α-tocopherol (Ghosh et al.,
2017)
Flower Ethanol DPPH Triterpenoid/steroids (Sianipar et al.,
2018)
Seeds Methanol DPPH, FRAP Total phenolic content (Omar et al.,
2020)
Leaves Aqueous DPPH, ABTS Polyphenols (Yap et al., 2020)
Leaves Methanol Phosphomolybdenum method Flavonoids (Ibrahim and
Ghareeb, 2020)
Fruit Papaya juice powder FRAP, ORAC, specific ROS – (Jarisarapurin
scavenging activities et al., 2019)
Seeds Methanol DPPH, FRAP, Metal chelating Kaempferol-3-glucoside, p-coumaric acid ferulic acid, caffeic acid, p- (Kadiri et al.,
assay hydroxybenzoic acid, quercetin-3-galactoside 2017)
Seeds Hexane, ethyl acetate, methanol DPPH, FRAP, TBARS Octadecanoic acid, oleic acid, n-hexadecanoic acid, 14- methyl-, (Agada et al.,
and aqueous methyl ester, 11-octadecenoic acid, methyl ester, and pentadecanoic 2020)
acid
Peel Aqueous DPPH, ABTS+ assay Proteins and phenolic groups (Kokila et al.,
2016)

MBP (Maltose binding protein) at its N terminal protease activity helps mosquitoes of C. quinquefasciatus, out of 200 mosquitoes, died after
in the digestion of MBP‐tag and leads to the isolation of recombinant 5 h of smoke. IR study provides information about the nature of the
PaMsrB1. The purified recombinant protein PaMsrB1 showed the active component, polyhydroxy aliphatic amide (Rawani et al.,
reductase activity against methionine sulfoxide (MetSO), Dabsyl 2012). One research study showed that peel and seed aqueous extract
MetSO in the presence of dithiothreitol. Various proteins that interact of papaya has a larvicidal activity for Aedes aegypti. It was also found
with PaMsrB1 were obtained and identified by affinity chromatogra- that seed extract has higher larvicidal activity in comparison to peel
phy and LC‐MS/MS. These results provide a platform to understand extract. Perhaps, due to the presence of phytochemicals in extract such
the defense mechanism of PaMsrB1 against anti‐oxidative stress Fur- as flavonoids, tannins, and alkaloids (Hayatie et al., 2015). Another
ther, details of the antioxidant activities of C. papaya is summarized study showed that leaf, bark, root, and seeds possess insect repellent
in Table 2. activity against Aedes aegypti. It was also found that crude ethanol
extract was much effective in controlling the vector as compared to
aqueous extract (Malathi and Vasugi, 2015). Also, it was found that
5.2. Insecticidal and repellent responses C. papaya leaf extract has the potential to develop as a source of natu-
ral insecticide against chikungunya (Kovendan et al., 2012a, 2012b),
The seed extract of C. papaya (petroleum‐ether, benzene, ethyl filaria (Rawani et al., 2009) and malaria vector mosquito (Sesanti
acetate, chloroform: methanol (1:1 v/v) and crude extract can be use- et al., 2014; Kovendan et al., 2012a, 2012b). Leaf extract of papaya
ful for their larvicidal, pupicidal, adulticidal, repellent effects and in ethanol has the potential to act as natural insecticides to control
smoke toxicity against Culex quinquefasciatus, malaria and Anopheles the population of German cockroaches which are known to resistant
stephensi, respectively. The mortality rate of A. stephensi and C. quinque- against synthetic insecticides (Rahayu et al., 2020). Another research
fasciatus at 0.5% concentration is more effective. It was found that the study revealed the toxic effect of leaf extract against Mustard aphid
repellant effect against both female mosquitoes with protection per- which is an important insect pest of various mustard species (Ujjan
centages 78 and 92 respectively. Protection time against biting was et al., 2014). Papain (enzyme) found in papaya has also been reported
4 h for C. quinquefasciatus and 5 h for A. stephensi. One research study for its insecticidal activity (Konno et al., 2004).
showed toxic smoke test, 186 mosquitoes of An. stephensi and 190

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5.3. Antibacterial activity Table 3

Antimicrobial activities of Carica papaya.
Published reports are available which showed that the various parts Parts Type of extract Activity against Reference
of papaya have significant antimicrobial activity. Oleic acid isolated used
from the seed and was tested for its chemo‐preventive action on live
Seeds Methanol E. coli, K. pneumonia, P. (Singh et al.,
fish which was infected with pathogenic bacteria named Klebsiella vulgaris 2020a, 2020b,
PKBSG14 and it was found that drug bioavailability increases with 2020c)
an increase in oleic acid (Ghosh et al., 2017). Research investigation Seeds and leaves n-hexane, ethanol, ethyl E. coli, S. aureus,
was carried out to check the antimicrobial activity of fresh and dried acetate and diethyl ether Bacillus subtilis and
C. albicans
leaves extracts (acetone, aqueous, and ethanol) of papaya by disc dif- (Prasetya et al.,
fusion method. Results exhibited that aqueous extracts were less effec- 2018)
tive as compared to organic extracts. It was also found that a fresh Leaves Methanol and E. coli, S. aureus and C. albicans (Callixte et al.,
sample was more efficient against Gram‐negative bacteria and the aqueous 2020)
Seeds Methanolic E. coli, S. aureus, B. subtilis and (Sahni, 2020)
dry sample showed great efficiency against both Gram‐positive and
P. aeruginosa
Gram‐negative bacteria (Alabi et al., 2012). Research investigation Seeds Petroleum ether, E. coli, S. aureus, B. subtilis, (Sofi et al., 2016)
reported that ethyl acetate, chloroform, hexane, methanol, acetone, ethanol and Salmonella typhium and
hot water, ethanol and petroleum ether leaf extracts of papaya extract aqueous Pseudomonas fluroscens
exhibited antibacterial activity (Baskaran et al., 2012). Adejuwon et al. Seeds Chloroform Klebsiella PKBSG14 (Ghosh et al., 2017)
Peel Aqueous E. coli, S. aureus, B. subtilis and (Kokila et al., 2016)
(2011) also reported antimicrobial activity of that methanolic and
K. pneumonia
aqueous root extract papaya against seven were bacteria and four were Fruit Aqueous S. aureus and P. aeruginosa (Sasirekha et al.,
fungi. Anibijuwon and Udeze (2009) reported that papaya leaf extract 2018)
showed antimicrobial activity against Pseudomonas aeruginosa. The leaf Leaves Aqueous E. coli and Bacillus cereus (Syafiuddin et al.,
2017)
extract showed superior effects against all Gram‐positive bacteria as
Leaves Aqueous E. coli, S. aureus, B. subtilis and (Muthukumar
compared to Gram‐negative bacteria. P. vulgaris et al., 2016)
Callixte et al. (2020) also reported the antibacterial activity of Leaves Aqueous E. coli, S. aureus and B. subtilis (Anantharaman
papaya leaf aqueous and methanolic extracts against Escherichia coli, and George, 2016)
Staphylococcus aureus, and Candida albicans. The antibacterial activity Leaves Ethanolic and E. coli, Coliform bacillus, (Airaodion et al.,
aqueous Staphylococcus epidermidis, 2020)
of the methanolic extract was significant compared to aqueous extract.
Streptococcus viridans and
Another report showed that methanolic seed extract was examined for Salmonella typhi
the antibacterial activity by using Agar well diffusion method. This Peel Aqueous E. coli, S. aureus, B. subtilis, B. (Tripathi and
activity was tested against S. aureus, Bacillus subtilis, E. coli, and P. pumilus, K. pneumonia, Sirohi, 2016)
Aspergillus niger and Candida
aeruginosa (Sahni, 2020). The maximum zone of inhibition was against
tropicalis
S. aureus 16 mm followed by P. aeruginosa 14 mm. Recent research Peel Aqueous S. aureus (Agarwal et al.,
investigation reported that methanolic extract of papaya seed was 2015)
tested for its antibacterial activity against E. coli, Klebsiella pneumonia, Peel Aqueous E. coli and S. aureus (Balavijayalakshmi
and Pseudomonas vulgaris by using the Agar disc diffusion method. The and Ramalakshmi,
2017)
extract showed antimicrobial activity in the following order E. coli >
Latex Aqueous S. aureus, P. aeruginosa, K. (Sharma, 2016)
P. vulgaris > K. pneumonia (Singh et al., 2020a, 2020b, 2020c). NPs aerogenes and Pseudomonas
prepared different plant parts have also shown antimicrobial activity desmolyticum
for example silver nanoparticles (Ag‐NPs) were obtained fruit extract Leaves Aqueous E. coli, P. fluorescens, B. subtilis (Gupta et al., 2017)
and Salmonella typhi
exhibited a dose‐dependent manner antibacterial activity against P.
aeruginosa and S. aureus (Sasirekha et al., 2018). Renganathan et al.
(2019) used leaf extract for the synthesis of Ag‐NPs and these NPs per-
formed excellent antimicrobial activity against P. aeruginosa and E. coli.
Ag‐NPs prepared from the peel of C. papaya were tested for antimicro- indica) effective in the treatment of diarrhoea. DAS‐77 was tested on
bial activity against two bacterial strains E. coli and S. aureus. The zone mice and the result showed that DAS‐77 possesses antidiarrhoeal activ-
of inhibition was greater for Gram‐negative (bacteria in comparison to ity. In another study antidiarrheal activity of leaf aqueous extract of C.
Gram‐positive bacteria (Balavijayalakshmi and Ramalakshmi, 2017). papaya was tested in rats’ model and found that extract has good
Ag‐NPs were fabricated from leaf extract showed antibacterial activity antidiarrheal activity and the extract was observed to be safe at
(Banala et al., 2015). Kalpana et al. (2018) have also synthesized Ag‐ 200 mg/kg in the case of rats model (Zanna et al., 2017).
NPs from leaf extract and reported their antimicrobial activity against
S. aureus and P. aeruginosa (Kalpana et al., 2018). Jain et al. (2009) 5.5. Wound-healing activity
used green un‐ripened papaya fruit extract for Ag‐NPs and these NPs
showed antibacterial activity against E. coli and P. aeruginosa. Antimi- Various skin disorders as well as wounds can be cured by papaya.
crobial activities of C. papaya against various types microorganisms The ethanolic papaya seed extract was tested in Sprague‐Dawley rats,
are presented Table 3. for its wound‐healing activity. Results showed that the seed extract
assists wound healing in rats (Nayak et al., 2012). C. papaya loaded
5.4. Antidiarrheal responses PVA/Gelatin nanofibrous was prepared from leaves of C. papaya by
electrospinning process. The fabricated nanofibers were hydrophilic
Prabhu et al. (2017) reported that the chloroform extract (25 mg/ and showed wound healing activity. It also exhibited strong antibacte-
mL) of raw C. papaya and acetone extract (25–0.39 mg/mL) of ripe C. rial activity against both S. aureus (Gram‐positive) and E. coli (Gram‐
papaya had essential antidiarrheal activity against the gut pathogens. negative) (Ahlawat et al., 2019). In a research investigation, the effect
The antidiarrheal activity of ripe C. papaya extract was extensively of aqueous extract of the root of C. papaya on wound healing in albino
seen against Plesiomonas shigelloides with ranges from 50 mg/mL rats was checked and root extract showed wound healing activity. It
0.39 mg/mL. Akindele et al. (2011) reported that DAS‐77 (herbal mix- was concluded that the extract‐treated wound shows remarkable
ture prepared dried root of C. papaya with young bark of Mangifera wound healing activity like standard FSC (Framycetin sulphate

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Table 4
Effect of Carica papaya extract on various cancer cell lines.

Cancer cell lines Preparation – plant part Effects Reference

Prostate cancer cell Use of papaya leaf juice Anti-proliferative effect on prostate cancer cell (Pandey et al.,
2018)
Prostate cancer cells Methanolic extract of black seed Inhibition of prostate cancer cell line (Alotaibi et al.,
2017)
MCF7 breast cancer cell line Petroleum ether extract of aerial Inhibition of MCF7 (breast) cancer cell line (Khaled and
part of C. papaya Gerda, 2013)
MCF7 breast cancer cell line Aqueous extract of C. papaya Antiproliferative effect on MCF7 breast cancer cell line (García-Sols
flesh et al., 2009)
Breast cancer (MCF-7) C. papaya extract with ethanol Inhibition of MCF-7 cell line (Jayakumar
(50–640 g/mL) and
Kanthimathi,
2011)
Leukemia cell line HL-60 Aqueous extract of C. papaya Induce apoptosis (Nakamura
seed et al., 2007)
Human colon CCD-18Co cells Aqueous extract of C. papaya Cytotoxic effect (Miyoshi et al.,
fruit 2007)
Cancerous cell lines of lung, colon, ovarian, Aqueous extract of papaya Concentration-dependent anticancer effect on each of the cancerous (Morimoto and
lymphoma, breast, neuroblastoma, uterine, liver, leaves cell lines and by suppressing DNA synthesis. Dang, 2006)
Pancreatic and stomach cancer
Leukemia HL-60 cells Use of extract of papaya seed or Use of Extract of seed: superoxide generation is inhibited in a dose- (Nakamura
pulp with n-hexane and pure dependent manner in comparison with pure benzyl isothiocyanate. and Miyoshi,
benzyl isothiocyanate. No change showed at 100 g/mL by pulp extract 2006)
Breast cancer cell line (T47D) Protein fraction containing RIPs Cytotoxic effect: IC50 = 2.8 mg/mL (Hirose et al.,
isolated from leaves 1998)

cream). In comparison with control (80.38%), tested animals reveal prostate cancer cells (Alotaibi et al., 2017). Another research study
89.40% reduction in wound part after treated by latex of C. papaya reported that papaya leaf juice has also an anti‐proliferative effect on
(Tiwari et al., 2011). In one research study, C. papaya stem was ana- prostate cancer cells (Pandey et al., 2018). Anticancer activities of C.
lyzed for its wound healing property in albino rats. Ten albino rats papaya against various cancer cell line are presented Table 4.
were used as experimental animals in two groups. The first group of
five animals was treated with an antiseptic named Betadine, whereas
5.7. Anti-malarial activity
other groups of five animals were treated with ointment obtained from
C. papaya. Initial and mean size of the wound every two days interval
There were several reports available that support the anti‐malarial
showed no major effect. The final wound size in millimeters after fif-
activity of C. papaya. According to Suleman et al. (2018) papaya along
teen days showed a major effect. This result suggested the wound heal-
with other plants used by peoples in the treatment of malaria and
ing activity of C. papaya in albino rats (Ancheta and Acero, 2016).
related symptoms. Another study also revealed about antimalarial
effect of methanolic extract of C. papaya in mice on Plasmodium berghei
NK65 strain (Longdet and Adoga, 2017). Also, leaf extract was tested
5.6. Anticancer activity
against Plasmodium falciparum 3D7 and Dd2 strains. Carpaine was the
most active alkaloid extract in dichloromethane leaf extract and dis-
In vitro investigation of C. papaya suggested that it has anti‐cancer
played good activity against both strain of Plasmodium falciparum
properties. The plant contains an enzyme, namely papain which is a con-
IC50 of 2.01 ± 0.18 μg/mL (4.21 μM) and 2.19 ± 0.60 μg/mL
stituent of papaya and very helpful in cancer treatment. Fibrin breaks
(4.57 μM). This alkaloid is highly selective against the parasite and
down by papain which coats the tumor cells into amino acid. The pig-
non‐toxic to healthy uninfected R.B.C (Teng et al., 2019). Further,
ment lycopene is found inside the papain which is highly reactive
methanol, chloroform, petroleum ether extract of fruit rind, and roots
towards free radical and oxygen. Papaya also contains isothyocynate
of papaya were tested against Plasmodium berghei in mice for their
which protects the breast, prostate, pancreas, lung, leukemia, and colon
antiplasmodial activity. The result showed that petroleum ether and
cancer (Fauziya and Krishnamurthy, 2013). In a research study, it was
chloroform extract of C. papaya fruit rind has considerable antiplas-
revealed that the leaf extract of C. papaya can prevent the progression
modial activity in a dose‐dependent manner but petroleum ether
of cancerous cells. Various markers such as CA15‐3 and LDH are the
extract had the highest antimalarial activity (Zeleke et al., 2017).
important biochemical parameter for the detection of cancerous cells;
and it was found that the leaf extract in a dose of 200 mg/kg body weight
has a significant effect to decrease both markers in the treatment of can- 5.8. Anti-dengue activity
cer (Gurudatta et al., 2015). Petroleum ether, ethyl acetate, chloroform,
and methanol (80%) extracts of aerial parts C. papaya were analyzed Chandrasekaran et al. (2018) have reported that the larvicidal effi-
for their anticancer effect against three types of cancer cells such as ciency of chloroform, methanol and aqueous extracts of C. papaya
UACC62 (melanoma) TK10 (renal) and MCF7 (breast) cancer cells. It latex against larvae of C. quinquefasciatus and A. aegypti which were
was concluded that the petroleum extract of papaya aerial parts had a effective in a was dose‐dependent manner. Order of toxicity effect is
significant effect on MCF7 (breast) cancer cells (Khaled and Gerda, as chloroform extract > methanol extract > aqueous extract. One
2013). One research report concluded that black seed from yellow ripe report on the clinical trial of C. papaya suggested that improve in pla-
papaya has a direct effect to reduce the growth of prostate cancer cells. telet count of dengue patients and faster improvement (Singh and
Methanolic extract of black seed (ripe papaya) and white seed (unripe Rawat, 2017). C. papaya leaf juice prepared by the traditional method;
papaya) was tested against the prostate cancer cell line. It has been and two tablespoons of juice were given to 5 dengue patients three
reported that the black seed extract is effective against prostate cancer times/day after 6 h. It was found that leaf juice causes a significant
cells whereas the white seed shows a stimulating effect on pre‐existing intensification in the platelet counts within 24 h of treatment (Kala,

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Table 5
Nanoparticle fabrication from Carica papaya and their applications.

Nanoparticle Characterization techniques Shape Size (nm) Applications Reference

Ag UV–Vis, FTIR, XRD and HRTEM FCC 12 ± 6 Anticancer and antibacterial activities (Chandrasekaran et al., 2016)
Ag UV–Vis, FTIR and XRD FCC 28 Antioxidant activity (Kokila et al., 2016)
Ag UV–Vis, FTIR, XRD, FESEM, _ 50–70 Antibacterial activity (Sasirekha et al., 2018)
Fluorescence
Ag FTIR, XRD, SEM, TEM and EDS/EDX Spherical 5–50 Bactericidal activity (Banala et al., 2015)
Ag UV–Vis, FTIR – 35–50 Mercury analysis (Firdaus et al., 2016)
Ag UV–Vis, FTIR, XRD, AFM and DLS Spherical 7–32 Antimicrobial activity and anti-dengue (Renganathan et al., 2019)
agent
Ag UV–Vis Spherical – Antimicrobial activities (Tripathi and Sirohi, 2016)
Ag UV–Vis, XRD and DLS _ 20 Antibacterial activity (Agarwal et al., 2015)
Ag UV–Vis, FTIR, XRD, SEM, TEM and Spherical 16–20 Antibacterial activity (Balavijayalakshmi and Ramalakshmi,
SAED 2017)
Ag FTIR, FESEM, SEM and EDX Spherical 13–69 Antibacterial activity (Syafiuddin et al., 2017)
Au UV–Vis, XRD and TEM _ 150 ± 1.02 Cytotoxic and proliferative activities (Princely et al., 2020)
Au UV–Vis, FTIR, XRD, SEM and HRTEM Spherical and 2–20 Antimicrobial and anticancer activities (Muthukumar et al., 2016)
triangular
Ca FTIR, XRD and SEM _ 89–148 Antibacterial and photocatalytic (Anantharaman and George, 2016)
activities
Cu UV–Vis, FTIR, XRD, SEM and DLS Rod 140 Photocatalytic degradation (Sankar et al., 2014)
Sn FTIR, XRD, SEM, TEM, EDS and XPS __ 7.10 LPG gas sensing (Jadhav and Kokate, 2019)
Ti FTIR, XRD and FESEM Spherical 15.6 Photocatalytic activity (Kaur et al., 2019)
Zn UV–Vis, FTIR, PXRD, FESEM, TEM Spherical ~50 Photocatalytic activity (Rathnasamy et al., 2017)
and EDS
Zn FT-IR, XRD, SEM, TEM and XPS Flower like 10.2 ± 0.6 Catalytic activity (Saikia et al., 2015)
morphology
Zn UV–Vis, FTIR, XRD, SEM, TEM and Hexagonal 11–26 Photocatalytic and antibacterial (Sharma, 2016)
HRTEM activities

2012). An increase in platelet count was observed when a patient was pliment mediated hemolytic assay and lymphocyte proliferation assays
given C. papaya leaf extract tablet three times daily for five days and it (Mojica‐Henshaw et al., 2003). Further, leaf extract was examined for
was suggested that this effect may be due to the expression of the gene its anti‐inflammatory effect in rats using edema, granuloma, and
responsible for platelet construction named as platelet‐activating fac- arthritis models and it was found that there were significant reduction
tor receptor gene (Kasture et al., 2016). Another investigation has also paw edema, granuloma formation, and inflammation in rats (Owoyele
shown that the leaves of C. papaya have a promising effect on to et al., 2008). Abdullah et al. (2011) have also reported the role of the
increase in the platelet counts of a dengue patient (Kapoor, 2017). fruit of papaya as an anti‐inflammatory response mediated through T‐
cells (Tregs).

5.9. Anti-inflammatory and immunomodulatory responses

6. Nanoparticle fabrication from papaya and their applications
Papaya contains an extensive range of secondary metabolites such
as alkaloids, tannins, flavonoids, saponins, which have been shown to Nanotechnology is emerging science and uses both physical and
a marked effect to reduce chronic inflammatory reaction. Proteolytic chemical methods for the synthesis of nanoparticles (NPs). In recent
enzymes that are present in papaya such as papain and chymopapain years, researchers have shown a keen interest in the synthesis of NPs
also showed an anti‐inflammatory effect as well as an effect on using the plant's system (Bachheti et al., 2020a, 2020b, 2020c;
immunomodulation (Rose et al., 2006; Mohr and Desser, 2013; Husen, 2020a, 2020b, 2020c; Joshi et al., 2019; Painuli et al., 2020;
Rakhimov, 2001). Papain in combination with other proteolytic Raja and Husen, 2020; Siddiqi and Husen, 2020). Many research stud-
enzyme such as trypsin and chymotrypsin reduce TGF‐ β1 level in ies are available which have highlighted the use of C. papaya for the
osteomyelofibrosis, rheumatoid arthritis and herpes zoster (Desser synthesis of NPs (Table 5). For instance, titanium dioxide (TiO2) NPs
et al., 2001). Alkaloids of papaya such as choline and nicotine showed were prepared using the C. papaya leave extract. X‐ray diffraction
anti‐inflammatory potential (Aldhous et al., 2008; Mabley et al., 2011; (XRD), Transmission electron microscopy (TEM), Field emission scan-
Nizri et al., 2009; Zhou et al., 2012). In vivo research was performed to ning electron microscopy (FE‐SM), and FTIR technique were used to
investigates the immunomodulatory activities of fruit (Lima de characterize the synthesized NPs which showed tetragonal crystal
Albuquerque et al., 2010). In a study, it has been reported that trans- structure of TiO2 with an average size 15.6 nm (Kaur et al., 2019).
genic and native papaya fruit (both ripe and unripe) have significant Kalpana et al. (2018) synthesized Ag‐NPs using C. papaya leave extract
immunomodulatory properties. These immunomodulatory effects and characterized by UV–Vis, FTIR, and XRD which revealed that NPs
were observed in the ovalbumin sensitized mouse model. A remark- were spherical in shape and size varies between 5 and 50 nm. Gold
able decrease in OVA‐specific IgE titre was noticed with native green nanoparticles (Au‐NPs) were used as a carrier for active compounds
papaya fruit, whereas an increase in OVA‐specific IgG2a titre was (MCP I) of C. papaya seeds extract and used as an innovative male con-
observed with green and ripened papaya fruit (Chen et al., 2011). traceptive in albino rats (Mohammad, 2019). AuNP‐MCP I was charac-
The ripened transgenic papaya fruit has a significant increase in IgM terized by TEM analysis showed that NPs were monodisperse /
level which leads to enhanced humoral immunity (Sadek, 2012). spherical with size 50 nm. Green un‐ripened C. papaya fruit extract
Another study also showed that the seed extract of this plant has both was used for the synthesis of Ag‐NPs. UV–Vis, FTIR, and scanning elec-
anti‐inflammatory activity and immunomodulatory effects. For tron microscopy (SEM) was used to characterize Ag‐NPs. The size of
instance, the bioactive reactions and immunomodulatory effect of NPs was found to be 15 nm and cubical (Jain et al., 2009). Ag‐NPs
crude seeds extract of this plant were investigated in vitro using com- were prepared using C. papaya fruit extract and were characterized

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Puree
Concentrate
Jelly

Canned Jam
slices/ chunks

PAPAYA BASED
PROCESSED
FOOD AND
OTHER
PRODUCTS Candied
Mixed fruit
beverages

Wine Pickle

Fig. 3. Papaya-based processed food and beverages.

by using FESEM, XRD, UV–vis, and FTIR spectroscopic technique. global level. Thus, to increase the self‐live of papaya fruit, they can
From the optical size, these Ag‐NPs reveal high mono dispersed nature. be used for the development of processed food products and other
FESEM analysis revealed the size of these NPs ranges from 50 to 70 nm associated products. Lots of works reported on the in this area, for
(Sasirekha et al., 2018). Another study exhibited that the Ag‐NPs was example, papaya is used for making jam with other substances (Aziz,
synthesized from C. papaya leaf extract. The shape and size of Ag‐NPs 2020; Cruz et al., 2019; Parsi‐Ros, 1976; Teangpook and
were characterized by SEM, TEM, XRD, EDX, and FTIR. The result Paosantong, 2013), jelly (Hunaldo et al., 2020; Mie, 2013; Yi‐zhuo
showed that the size of Ag‐NPs was a range between 50 and 250 nm et al., 2013) pickle (Kumar et al., 2019a, 2019b; Nurul and Asmah,
and was spherical (Banala et al., 2015). In another study, C. papaya 2012; Su and Liu, 2006), candied fruit (Ahmad et al., 2005; Chan
leaf extract used for the synthesis of Ag‐NPs and synthesized NPs and Cavaletto, 1978; Cherian and Cheriyan, 2003; Jadhav et al.,
was spherical. AFM showed that the size of these NPs ranges between 2012; Kumar et al., 2019a, 2019b) puree (Brekke et al., 1972; Nath
7 and 32 nm (Renganathan et al., 2019). TiO2‐NPs prepared from C. and Ranganna, 1981; Ocoró‐Zamora and Ayala‐Aponte, 2013;
papaya leaves showed amazing photocatalytic efficiency (91.19%) Tulamandi et al., 2016), wine (Cholassery et al., 2019), mixed bever-
towards photodegradation of RO‐4 dye (Kaur et al., 2019). Very ages (Atif and Mishra, 2019; Bahnas et al., 2019; Boghani et al., 2012;
recently, C. papaya leaf extract was used to synthesize bimetallic Rodriguez and George, 1971; Saravana‐Kumar and Manimegalai,
NPs. TEM analysis revealed the information about the size of NPs 2001; Ukwuru and Adama, 2003; Yadav et al., 2013), canned slices/
which has a range of 150 ± 1.02 nm (Princely et al., 2020). Further, chunks (Lynch et al., 1959; Nath and Ranganna, 1981), concentrate
NPs synthesized from different parts of C. papaya along with their (Kaleemullah et al., 2002; Kandasamy and Varadharaju, 2014),
applications are summarized in Table 5. spray‐dried enzyme (Chang et al., 2020), ice cream (Omar et al.,
2020). Overall, the various products obtained from papaya fruits are
illustrated in Fig. 3.
7. Use of papaya in processed food and beverages

It has been already reported that the papaya fruit grows very fast, 8. Use of papaya waste
cultivated throughout the year and thus production rate is high.
Hence, the main problem exists is that how to use entire products, Huge quantities of papaya are produced every year and utilized for
otherwise it will spoil. Usually, papaya fruits are used not often at a different purposes; thus, a large number of wastes and by‐products are

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Fig. 4. Various application of papaya and their products.

generated. Approximately the percentage of waste of papaya peels of the human body. Various types of cosmetic products are available
12% and papaya seeds 8.5%, of the fruit weight, are reported in the market for the use of different parts of the body. Herbal cosmet-
(Pathak et al., 2019). The papaya peel contains vitamins such as vita- ics are in great demand in the current situation to avoid damage
min A, vitamin C, riboflavin, thiamine, and niacin. It is a source of phe- caused by chemical cosmetics. Bioactive components of botanicals
nol, alkaloid, flavonoid, tannin, and saponin (Chukwuka et al., 2013). are used in different herbal cosmetic products such as face cream, face
It also contains different valuable minerals, for instance, calcium, packs, lotions, hair products such as oil and conditioner. They are pre-
sodium, potassium, phosphorus, and magnesium (Asghar et al., ferred for their safe use with no side effects. Herbal cosmetics are cos-
2016; De Matuoka et al., 2013). Due to this richness in vitamin, min- metics that use bio‐ingredients which have no side effects on the skin
erals, and phytochemicals, papaya peel is used for different purposes or hair (Kapoor, 2005). Papaya also has a great effect on skin and hair
for example in cosmetics (Aravind et al., 2013; Yogiraj et al., 2014) according to many investigations. Sadek (2012) have reported that the
for growth of microorganisms (Chelliappan and un‐ripened fruit of papaya can be used as an ingredient for facial prod-
Madhanasundareswari, 2013; Espin and Islam, 1998) extraction of ucts such as face creams. In this, the fruit pulp of papaya is used to
sugars (Kumar et al., 2012), biofuel (Raj et al., 2012) in wastewater remove blemishes on the skin and to make it soft. In another study,
treatment (Abbaszadeh et al., 2014; Abbaszadeh et al., 2016; it was found that papaya can be used as an ingredient in an anti‐
Mekonnen et al., 2015; Teja et al., 2013) nanoparticles synthesis acne face pack for its bleaching and antioxidant property (Priya,
(Agarwal et al., 2015), meat tenderizer (Islam and Molinar‐Toribio, 2017). Several commercial as well as other application of papaya
2013), as a binder in ceramics (Rachtanapun et al., 2010), and in and their products is illustrated in Fig. 4. In a research study, it was
toothpaste preparation (Chowdhury et al., 2013). The chemical com- found that enzyme papain can be used in the manufacturing of skin
position of seed oil of papaya reported containing oleic acid 47.7%, cleansing products as it has high activity in the breakdown of proteins
linoleic acid 37.3%, palmitic acid 6%, and used for the generation of into smaller peptides and amino acids so it can easily dissolve dead
biodiesel (Agunbiade and Adewole, 2014; Anwar et al., 2018) More- cells present on the skin (Setiadi and Anindia, 2018). Currently, sev-
over, recently (Gohain et al., 2020) have reported the use of papaya eral papaya‐based skincare products are available in the market. Fur-
stem as a source of heterogeneous catalyst for biodiesel production. ther, antioxidants present in papaya also makes it suitable for the
Overall, the waste materials obtained from papaya have been used soap formulations. Solid soap was prepared using crude papain
for the production of a number of products. However, most of the data enzyme from papaya; and solid soap effectively removes dirt than
is based on laboratory research, thus a pilot plant trial is required. Fur- the soap without enzyme. The soap different formulation was checked
ther, the physicochemical properties of papaya peel vary with the geo- for antioxidant activity and the best formation was Formula IV (addi-
graphical location, varieties, and season so on, and may affect the tion 30% papaya fruit as antioxidant and 1.5% crude papain enzyme)
processing, and other associated activities. Thus, an extensive research had a value of fatty acid 79%; pH 10.35; specific density 1.0595 gr/
investigation is required. mL; alkali‐free 0.108% and foamability 78% after stand for 5 min
(Setiadi and Anindia, 2018). Crude papain enzyme is added as an
9. Commercial products from papaya active ingredient of solid soap formulation with the antioxidant origi-
nated from fresh papaya and found to be useful for human skin health.
The cosmetic world is a major industry in today's time. Cosmetics Antioxidant features of soap caused by active substance from papaya
are used throughout the world for improving the general appearance fruit such as ascorbic acid, α‐tocopherol, beta carotene, niacin vitamin

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B1and flavonoids have been already reported (Özkan et al., 2011). feed, as a binder in ceramics. Various plant parts are also used in
According to a research study, various parts of C. papaya such as latex, nanoparticle synthesis which enhances its chances of present and
leaves, seeds have different components with various medicinal prop- future applications. FAO has also suggested that at global level, the
erties. The latex of C. papaya contains proteolytic enzyme, papain use of papaya and its products are increasing every year due to its
which is used as an ingredient in ointment named panafil. This oint- numerous applications. Taken together, studies have shown that
ment is used to clean the wound and for its healing properties papaya can play a key role in the health care sector, pharmaceutical
(Bertran, 1997). Leaves of C. papaya contain an alkaloid named car- sector, in the food processing and herbal cosmetic sectors, and helpful
paine which has spasmolytic action on smooth muscles, as well as in growing the economics of the different countries. Further, to utilize
amoebicidal properties. Mors et al. (2001) have suggested that papaya the papaya waste products some pilot plant trial is required for its full
plant has can be used in the drug industry. Chavan (2018) have also valorization. Moreover, further extensive research investigations are
reported papaya plant can be used for several commercial products. needed to explore the papaya plant growth and development at differ-
Overall, various parts of papaya plants have shown significant poten- ent geographical location/seasons/conditions for the production of
tial applications and a lot of products such as hair shampoo, jam, important phytochemical compounds which can be effectively uti-
pickle, syrup, dietary supplement, detergents, face lotions, papaya lized in some important drug formulation such as against the dengue
drinks, papaya enzyme tablets, moisturizers, and digestive enzymes fever.
are already available in the market.

Declaration of Competing Interest

10. Miscellaneous activities
The authors declare that they have no known competing financial
Studies have shown that the dietary fiber concentrates (DFC) were interests or personal relationships that could have appeared to influ-
produced as a product from C. papaya by treatment with ethanol and ence the work reported in this paper.
microwave drying. These fibers were found to have an antioxidant
effect. Extraction with ethanol was performed by 2.9 ml of ethanol/
gm of papaya pulp for 15 min followed by microwave drying which References
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