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TANG / www.e-tang.org
2014 / Volume 4 / Issue 1 / e2
Review
Papaya: A gifted nutraceutical plant - a critical review of recent human health
research
Kaliyaperumal Karunamoorthi1,*, Hyung-Min Kim2, Kaliyaperumal Jegajeevanram3, Jerome Xavier4, Jayaraman
Vijayalakshmi3
1Unit of Medical Entomology & Vector Control, Department of Environmental Health Sciences & Technology, College of Public
Health and Medical Sciences, Jimma University, Ethiopia; 2Department of Pharmacology, College of Korean Medicine, Kyung Hee
University, Seoul, South Korea; 3Annai Jagatha Hospital, Karuveppilankurichi - 606 110, Cuddalore District, Tamil Nadu, India;
4Government Siddha Medical College, Palayamkottai, Tamil Nadu, India
ABSTRACT
The plant kingdom is considered to be a repository of modern medicine, attributable to their rich source
of bio-active molecules and secondary metabolites. It is indeed the Nutraceuticals that enhance immunity
and ensure a healthier life because of their prophylactic and therapeutic values. Over centuries, papaya
[Caricaceae; (Carica papaya Linn.)] is a renowned nutritious and medicinal plant. Each part of the
papaya like root, stem, leaf, flower, fruit, seed, rinds, and latex has its own nutraceutical properties. It
serves as food, cooking aid, and Ethnomedicine to prevent and treat wide-range of diseases and disorders.
It has also been traditionally used as appetite enhancer, meat tenderizer, purgative, medicinal acne,
abortifacient and vermifuge. Over decades, a series of scientific attempts were made to authenticate the
nutraceutical properties of papaya. These studies validated that the papaya has antiplasmodial,
antitrichochramal, antitrichomonal, antidengue, and anti-cancer activities. They have also exhibited that
papaya possesses antiseptic, antiparasitic, anti-inflammatory, antidiabetic, and contraceptive features, and
it helps in the management of sickle-cell anaemia, HIV, heart diseases and digestional disorders too.
Nevertheless, the responsible bio-active molecules and their mode of actions remain indistinct and
imprecise, and this calls for further pharmacological and clinical research on them. Conclusively, papaya
is one of the naturally gifted plants; though its nutraceutical properties as a food or as a quasi-drug are
poorly understood or undervalued by people. Accordingly, this scrutiny, demand for instigation of public
health awareness campaigns to promote papaya consumption, so that the society shall acquire optimal
benefits of papaya and in turn prevent and alleviate various diseases and illness.
Keywords Carica papaya, traditional system of medicine, nutraceutical, phytotherapy
INTRODUCTION
Infectious diseases are major public health issues in the
resource-poor countries. They contribute to higher rate of
morbidity and mortality related indices, due to fragile primary
care settings and people’s low socio-economic status to access
the modern healthcare facilities. Despite recent scientific
advancement and globalization, WHO estimates that in the
developing countries, nearly 80% of the population remains to
rely upon the traditional system of medicine (TSM) as a
primary health care modality in the resource-constrained health
care settings (Karunamoorthi et al., 2013a). Globally, since
time immemorial, each and every society has had its unique
way of indigenous health practice system in order to treat
various ailments (Karunamoorthi, 2012a). TSM is one of the
centuries-old practices and long-serving companions to the
human kind to fight against various diseases and to lead a
healthy life. Every indigenous group has been using their
unique approaches of TSM practice where among, the Chinese,
Indian and African TMSs are world-wide renowned
(Karunamoorthi et al., 2012).
In the near past, the generalization of modern health care
services has posed immense threat to indigenous health
practices due to their potential speedy therapeutic effect.
However, even in the era of modern computational
pharmacology approach, traditional medicinal plants serve as
an important source and as a tool to treat various ailments in
the developing countries (Karunamoorthi et al., 2012). The
advent of most efficacious potent antimalarials such as
chloroquine and artemisinin are products of our precious
traditional knowledge of traditional medicinal plants. These
recent successes inspire and encourage many researchers to
investigate and validate the roles of traditional medicinal plants
as phytotherapeutic agents (Karunamoorthi et al., 2013b).
Herbal medicinal system has been postulated and
established through empirical observation and trial and error
experiments since time immemorial to maintain good health
and alleviate ailments and diseases (Karunamoorthi et al.,
2013a). The Tamil traditional medicinal system, the so called
Siddha system of medicine (SSM), which is an ancient
indigenous practice the flourished and practiced for many
centuries in Tamil Nadu, India, has the basic principle of the
SSM as, “food itself is a medicine” which was postulated by
the great 18 sages called Siddhars. The million-year old Siddha
*Correspondence: Kaliyaperumal Karunamoorthi
E-mail: karunamoorthi@gmail.com
Received October 14, 2013; Accepted February 7, 2014; Published
February 28, 2014
doi: http://dx.doi.org/10.5667/tang.2013.0028
© 2014 by Association of genuine traditional medicine
Papaya: A gifted nutraceutical plant
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2014 / Volume 4 / Issue 1 / e2
literature indicates that the plant-based therapeutic agents can
cure many chronic diseases (Karunamoorthi et al., 2012).
The term "nutraceutical" was coined from "nutrition" and
"pharmaceutical" in 1989 by Stephen DeFelice, MD, founder
and chairman of the Foundation for Innovation in Medicine
(FIM), Cranford, NJ (Brower, 1998). According to DeFelice,
nutraceutical can be defined as, "a food (or part of a food) that
provides medical or health benefits, including the prevention
and/or treatment of a disease" (Brower, 1998). Nevertheless,
the term nutraceutical as commonly used in marketing has no
regulatory definition (Zeisel, 1999) (Table 1).
Since time immemorial, humankind has heavily relied
upon plants as phyto-therapeutic agents to prevent/heal several
ailments. However, in the modern era, the pharmaceutical
industries have thrived by adopting modern scientific
techniques and novel bio-technological tools, and developed
several life-saving drugs, offering speedy recovery.
Subsequently, the preventive as well as curative potency of
nutraceutical plants are undervalued. In recent times, the
health-conscious people have started realizing the chronic side-
effects and persistent adverse health-hazards of conventional
medicines. This has paved the healthy-way towards the
unprecedented revived interest on nutraceutical plants.
Nutraceuticals enhance immunity and ensure quality of life in
terms of good health and longevity, providing a prophylactic
approach.
Papaya is a major fruit crops known since ancient time, as
nutritious and medicinal plant or herb (Table 2). It natives to
southern Mexico and Central America nevertheless presently it
is grown throughout the tropical regions of the world. The
existing studies establish that the people are using papaya as a
source of nutrition as well as phytotherapeutic agent by unique
mode of preparation subsequently by consuming their parts.
However, there is a paucity of data on efficacy and safety. In
this perspective, this scrutiny is an effort to exemplify on the
phytotherapeutic potentiality of papaya through data mining
techniques from the prior scientific studies. It also delineates
in relation to responsible active ingredients and their mode of
action. In addition, it evaluates the existing challenges for
future exploitation and development of affordable, accessible
and safest papaya-based phytotherapeutic agents in the future.
Data mining and extraction
Evidence acquisition
In order to collect appropriate research materials for the present
scrutiny, a detailed search on Scopus, Medline, Google Scholar
and Academic Search Premier Databases has been carried out
Table 1. Definitions
Definitions
Nutraceuticals
Any substance that is a food or a part of a food, which provides medical or health benefits, including the prevention
and treatment of disease.
Phytochemicals
Bioactive non-nutrient plant compounds in fruits, vegetables, grains and other plant foods that have been linked in
reducing the risk of major chronic diseases.
Traditional Medicine
WHO (2002) defines traditional medicine as including diverse health practices, approaches, knowledge and beliefs
incorporating plant, animal, and/or mineral based medicines, spiritual therapies, manual techniques and exercises
applied singularly or in combination to maintain well-being, as well as to treat, diagnose or prevent illness.
Table 2. Taxonomy of Carica papaya
Taxonomy of Carica papaya
Kingdom
Plantae
Division
Magnoliophyta
Class
Magnoliopsida
Order
Brassicales
Family
Caricaeae
Genus
Carica
Species
Papaya L.
Fig. 1. The exclusion and inclusion criteria for choosing the appropriate
research articles, notes and reviews for this narrative review.
272 Research articles and web-
links located through search
engines and important databases
144 Research/Review articles/Web-
links excluded:
35 Repeated
50 Not dealing with
relevant keywords
05 Not in English
54 Duplicates/repeated in
different databases
128 Research/Review/web-links included
in the first stage
126 Research articles
chosen
02 Research/Review excluded:
Containing only general
information
Papaya: A gifted nutraceutical plant
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2014 / Volume 4 / Issue 1 / e2
for the time period 1950 - 2013. A Boolean search strategy was
adopted and the keywords entered for search are “Carica
papaya”, “ Traditional medicine and papaya”, “Nutraceutical
and papaya”, “Papaya as a phytotherapeutic agent” and
“ Papaya and diseases” in differing orders, in order to extract
studies. The exclusion and inclusion criteria for choosing the
appropriate research articles, notes and reviews were shown in
Fig. 1 for this narrative review, and their bibliographic details
(authors, title, full source, document type and addresses) were
downloaded and maintained in a file.
Early history and distribution
The very earliest literary reference to papaya trees dates back to
1526, when they were found on the Caribbean coast of Panama
and Colombia and described by the Spanish chronicler Oviedo.
The history of papaya appears to be first documented by
Oviedo, the Director of Mines in Hispaniola (Antilles) from
1513 to 1525, where he describes how Alphonso de Valverde
took papaya seeds from the coasts of Panama to Darien, then to
San Domingo and the other islands of the West Indies. The
Spaniards coined it the name ‘papaya’ (Schery, 1952) (Table 3).
However, there are some reports that describes that this plant
has originated from the south of Mexico and Nicaragua (Chan
and Paull, 2008), while others suggest that the origin is from
the northwest of South America (Serrano and Cattaneo, 2010).
However, after the discovery of the New World, the papaya tree
has been spread widely throughout the tropics, most
particularly in Africa and Asia. It is a very popular fruit,
commonly cultivated and more or less naturalized in India,
where it was introduced as early as 1598 (Schery, 1952).
Ecology
Papaya is reported to tolerate annual precipitation of 6.4 to 42.9
dm (mean of 42 cases = 19.2), annual temperature of 16.2 to
Table 3. Vemacular name(s) of papaya in some of the important languages worldwide
NO.
Name of the Language
Vernacular Name(s)
1
Amharic
Papaya
2
Arabic
Fafay, Babaya
3
Bengali
Psppaiva, Papeva
4
Burmese
Thimbaw
5
Creole
Papayer, Papaye
6
English
Bisexual pawpaw, Pawpaw tree, Melon tree, Papaya
7
Filipino
Papaya, Lapaya, Kapaya
8
French
Papailler, Papaye, Papayer
9
German
Papaya, Melonenbraum
10
Hindi
Papaya, Papeeta
11
Indonesian
Gedang, Papaya
12
Javanses
Kates
13
Khmer
Ihong, Doeum lahong
14
Korean
파파야
15
Lao (Sino-Tibetan)
Houng
16
Luganda
Papaali
17
Malay
Papaya, Betek, Ketalah, Kepaya
18
Malayalam
Omakai
19
Marathi
Papai
20
Rajasthani
Eerankari
21
Sinhala
Pepol
22
Swahili
Mpapai
23
Tamil
Pappali, Pappayi
24
Telugu
Boppayi pandu
25
Thai
Ma kuai thet, Malakor, Loko
26
Tigrigna
Papayo
27
Vietnamese
Du du
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26.6°C (mean of 42 cases = 24.5), and pH of 4.3 to 8.0 (mean
of 33 cases = 6.1). Papaya is a tropical plant, killed by frost;
does not tolerate shade, water logging, or strong winds, and
may require irrigation in dry regions. It recuperates very slowly
from serious root or leaf injury. It can be grown well below
1,500 m in well-drained, rich soil of pH 6 - 6.5 (Duke, 1983).
Morphological description
Papaya is a small, frost-tender, succulent, broadleaved
evergreen tree that bears papaya fruits throughout the year.
Each tree typically has a single, unbranched, non-woody trunk
bearing the scars of old leaf bases. The trunk is topped by an
umbrella-like canopy of palmately lobed leaves. Large, fleshy,
melon-like fruits (papayas) hang in clusters attached to the
trunk top just under the leaf canopy (Fig. 2). Papaya typically
grows to 6 - 20' tall (container plants to 10' tall) and is most
noted for its edible melon-like fruit. Papaya tree sometimes
branches due to injury (Fig. 3) and it contains white latex in all
parts. The stem is cylindrical, 10 - 30 cm in diameter, hollow
with prominent leaf scars and spongy-fibrous tissue. It has an
extensive rooting system (Orwa et al., 2009).
Leaves spirally arranged, clustered near apex of the trunk;
petiole up to 1 m long, hollow, greenish or purplish-green (Fig.
4); lamina orbicular, 25 - 75 cm in diameter, palmate, deeply 7-
lobed, glabrous, prominently veined; lobes deeply and broadly
toothed (Orwa et al., 2009). The species plants are typically
dioecious (hermaphroditic), and maple trees are uncommon.
Hermaphrodite trees (flowers with male and female parts) are
Table 4. List of chemical constituents present in the various parts of papaya
NO.
Categories
Phytoconstituents
Plant Part(s)
1
Enzymes
Papain, chymopapain A and B, endopeptidase papain III and IV glutamine
cyclotransferase, peptidase A and B and lysozymes.
Unripe fruit (Latex)
2
Carotenoids
β carotene, crytoxanthin, violaxanthin, zeaxanthin.
Fruits
3
Alkaloid & Enzyme
Carposide, and an enzyme myrosin.
Roots
4
Glucosinolates
Benzyl isothiocynate, benzylthiourea, β-sitosterol, papaya oil, caricin and an
enzyme myrosin.
Seeds
5
Minerals
Calcium, potassium, magnesium, iron, copper, zinc.
Shoots and Leaves
6
Monoterpenoids
4-terpineol, linalool, linalool oxide.
Fruits
7
Flavoniods
Quercetin, myricetin, kaempferol.
Shoots
8
Alkaloids
Carpinine, carpaine, pseudocarpine, vitamin C and E, choline, carposide.
Leasves and Heartwood
9
Vitamins
Thiamine, riboflavin, niacin, ascorbic acid, α-tocopherol.
Shoots and Leaves
10
Carbohydrates
Glucose, sucrose, and fructose.
Fruits
Fig. 3. Papaya tree with branches
Fig. 2. Papaya leaves arrangement like an umbrella-like canopy and
melon-like unripe fruits hang in clusters attached to the trunk top just
under the leaf canopy.
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the commercial standard, producing a pear shaped fruit. These
plants are self-pollinated (Jari, 2009).
Flowers tiny, yellow, funnel-shaped, solitary or clustered in
the leaf axils, of 3 types; female flowers 3 - 5 cm long, large
functional pistil, no stamens, ovoid-shaped ovary; male flowers
on long hanging panicles, with 10 stamens in 2 rows,
gynoecium absent except for a pistillode; hermaphrodite
flowers larger than males, 5-carpellate ovary; occurrence
depends on the season or age of the tree (Orwa et al., 2009).
The female flowers give way to smooth-skinned green fruits
(Fig. 5) that ripen to yellow-orange with a yellow to pinkish-
orange flesh and central cavity of pea-sized black seeds (Jari,
2009).However, several distinct varieties of papaya have been
mentioned (Richharia, 1957; Sen, 1939), which vary in shape
and size of fruits, height of plants, etc.
Description on papaya fruit
Papaya is melon-like fruit, round to oblong in shape and 3 to 5
inches in diameter (Figs. 5-6). The skin is smooth and thin,
shading from green in immature fruits to deep orange-yellow
when ripe. The flesh, 1 to 2 inches thick, varies from pale
yellow to a deep salmon-pink in color and a mildly sweet. The
central cavity of the fruit contains many round black seeds (Fig.
7) (Low and Maretzki, 1982). There are two main types of
papayas produced: the small-sized Solo-type papayas (aka
Hawaiian papayas), usually weighing between 1.1 and 2.2
pounds per unit, and the large-sized papayas (aka Mexican
papayas), weighing up to 10.0 pounds per unit (EDI, 2012).
The ripe papaya fruits are rich in vitamins, amino acids,
calcium, iron, enzymes and so on (Tables 4 and 5). The protein
in papaya is highly digestible. The fruit is usually consumed
fresh but may be made into juice, pickles, preserves, jellies or
sherbets or may be served cooked like cucurbits (Schery, 1952).
Chemical constituents
Papaya is considered one of the most important fruits because it
is a rich source of antioxidant nutrients (e.g., carotenes, vitamin
C, and flavonoids), the B vitamins (e.g., folate and pantothenic
acid), minerals (e.g., potassium and magnesium), and fibre
(EDI, 2012). Papaya plant is laticiferous as they contain
specialized cells known as laticifers. The lactifiers secrete latex
and are dispersed throughout most plant tissues. The papaya-
latex is well known for being a rich source of the four cysteine
endopeptidases namely papain, chymopapain, glycyl
Fig. 4. Papaya unripe and semiriped fruits
Table 5. The phytomedicine contents of the 100 gm leaf, young fruit and ripe fruit of C. papaya
NO.
Name of the Phytonutrient
Papaya Plant Parts
Leaves
Unripe fruit
Ripe Fruit
1
Calories
79 cal
26 cal
46 cal
2
Vitamin A
18,250 SI
50 SI
365 SI
3
Vitamin B1
0.15 mg
0.02 mg
0.04 mg
4
Vitamin C
140mg
19 mg
78 mg
5
Calcium
353 mg
50 mg
23 mg
6
Hydrate Charcoal
11.9 gm
4.9 gm
12.2 gm
7
Phosphorus
0.0 gm
16 mg
12 mg
8
Iron
0.8 mg
0.4 mg
1.7 mg
9
Protein
8.0 gm
2.1 gm
0.5 mg
10
Water
75.4 gm
92.4 gm
86.7 gm
Fig. 5. Papaya tree with flower and unripe fruits
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endopeptidase and caricain (Azarkan et al., 2003) and the
content of latex may vary in fruit, leaves and roots. As the
papaya fruit ripen, the amount of laticifers cells that produces
latex decreases (OECD, 2005). Therefore, ripe papaya contains
less latex and other constituents.
The richness of enzymes in papaya juice has been known
since 1878 (Witmann, 1978). The most important enzyme
papain was characterized in 1968 (Drenth et al., 1968). The
enzymes chymopapain and papaya protease III were
characterized in the 1980s of the last century (Jacquet et al.,
1989; Zucker et al., 1985) These two important compounds like
papain and chymopapain are supposed to aid in digestion and
therefore they are widely used to cure the digestive disorders
(Huet et al., 2006). In addition, papain is used in meat
tenderizing, pharmaceuticals, beauty products, and cosmetics
(EDI, 2012). Besides, it has been used in brewing and wine
making, and in the textile and tanning industries. It is also used
to treat arthritis.
It is important to note that the level and amount of the
chemical compounds vary in the fruit, latex, leaves, and roots.
The phytomedicine contents of the 100 gm of leaf, young fruit
and ripe fruit of C, papaya are listed in Table 5. In addition,
plant parts from male and female trees differ in the quantity of
the compounds. For example, phenolic compounds tend to be
higher in male trees than female trees. The amount of fresh
papaya latex and dry latex (crude papain) also vary with the
gender and age of the tree. Female and hermaphrodite trees
yield cruder papain than the male trees and the older fruit yields
more than the younger fruit. However, the activity of the papain
is higher in the extracts from the younger fruit than the older
fruit. Cultivars also vary in the quantity of the compounds
(Cornel University, 2009). A recent study has reported that the
green, yellow and brown leaves of papaya contain various
phytochemicals, vitamins and minerals composition (Ayoola
and Adeyeye, 2010). Therefore, the papaya leaves can be seen
as a potential source of useful food and drug items.
Papaya as a nutraceutical: a healthy solution
The fruit is not just delicious and healthy, but the whole plant
parts, fruit, roots, bark, peel, seeds and pulp are also known to
have medicinal properties. Nutraceuticals enhance immunity
and ensure quality of life in terms of good health and longevity
(Fig. 8). The many benefits of papaya owed due to high content
of Vitamins A, B and C, proteolytic enzymes like papain and
chymopapain which have antiviral, antifungal and antibacterial
properties. The methanolic extract of the seeds and 2, 3, 4-
trihydroxytoluene (caricaphenyl triol) (200 μg/ml) showed
significant antifungal activity against Aspergillus flavus,
Candida albicans and Penicillium citrinium (Singh and Ali,
2011).
C. papaya can be used for treatment of a numerous diseases
like warts, corns, sinuses, eczema, cutaneous tubercles,
glandular tumors, blood pressure, dyspepsia, constipation,
amenorrhoea, general debility, expel worms and stimulate
reproductive organs and many, and as a result C. papaya can be
regarded as nutraceutical (Aravind et al., 2013). Papaya latex
has been suggested for many diseases in different parts of the
world (Warring, 1968). Chemopapain, a product of papaya, is
commercially produced as a drug for sciatic pain. Papaya latex
has been used as a vermifuge and has bacteriostatic effects on a
number of infectious organisms. Another commercial product
of papaya is papain, a proteolytic enzyme used to tenderize
meat (Cherian, 2000).
Nutraceutical – nutrients/herbals that may prevent illness
Obviously, it has been well-known that the food cannot
alleviate human immunodeficiency virus (HIV)/acquired
immune deficiency syndrome (AIDS) infection, or treat the
HIV virus, but it can positively improve the fitness and the
quality of life. The malnourished people with HIV are sick
more often than the nourished HIV infected individual and can
develop AIDS furiously. The HIV infected/immune-
compromised individuals are extremely vulnerable to
opportunistic infections and these infection can be prevented by
specialized nutritional supplement in terms of ingesting
phytonutrient-rich fruits particularly papaya very regularly.
Since papaya is a gifted nutraceutical plant, it offers an
opportunity for controlling various diseases, particularly
neurodegenerative diseases and in AIDS management
(Bonuccelli, 2012). Recent studies indicate that the papaya may
hold the cure to the deadly AIDS virus. Researchers in the
Philippines believe that eating papaya could help in boosting
the immune system and can reduce the viral load of HIV in
some patients. Papaya juice is sometimes used in
pharmaceuticals as it can be used to remove blemishes. Latex
obtained from unripe fruits is used in folk medicine to treat
warts and corns (Dass, 2010).
Fermented papaya preparation (FPP) (a product of yeast
fermentation of C. papaya) is a food supplement. Studies in
Fig. 6. The author with the unripen papaya fruit in Jimma zone,
Eyhiopia
Fig. 7. Papaya fruit cavity containing black seeds
Papaya: A gifted nutraceutical plant
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2014 / Volume 4 / Issue 1 / e2
chronic and degenerative disease conditions (such as
thalassaemia, cirrhosis, diabetes and aging) and performance
sports show that FPP favourably modulates immunological,
hematological, inflammatory, vascular and oxidative stress
damage parameters. Neuroprotective potential evaluated in an
Alzheimer's disease cell model showed that the toxicity of the
β-amyloid can be significantly modulated by FPP. Oxidative
stress-induced cell damage and inflammation are implicated in
a variety of cancers, diabetes, arthritis, cardiovascular
dysfunctions, neurodegenerative disorders (such as stroke,
Alzheimer's disease, and Parkinson's disease), exercise
physiology (including performance sports) and aging. These
conditions could potentially benefit from functional
nutraceutical/food supplements (as illustrated here with
fermented papaya preparation) exhibiting anti-inflammatory,
antioxidant, immunostimulatory (at the level of the mucus
membrane) and induction of antioxidant enzymes (Aruoma et
al., 2010). Papaya can be considered a medicinal food. Papain
is the lauded enzyme derived from the papaya that is
incorporated into several types of enzymatic health
supplements. Although the evidence is scant, some sources
even suggest that papain is helpful in fighting Hepatitis C.
Biological activities
Digestive system disorders
Papain extract is used as a treatment for certain intestinal and
digestive problems. Ingredients of the papaya fruit and the
processed fruit have been associated with a beneficial impact
on digestion or diseases (Aruoma et al., 2010; Forstner, 1971;
Ghoti et al., 2011; Marotta et al., 2011; Scolapio et al., 1999;
Somanah et al., 2012). The fruit is considered as a traditional
remedy for gastrointestinal functional disorders in countries
with papaya plants. However, only little evidence has been
produced with reference to its physiological effect in humans
and the proof of efficacy. In line with these, Muss et al. (2013)
studied the clinical effects of the papaya preparation called
Caricol® in a double blind placebo controlled study design and
found that the (Caricol®) contributes to the maintenance of
digestive tract physiology. It ameliorates various functional
disturbances, like constipation, heartburn, and symptoms of
irritable bowel syndrome (IBS). Nevertheless, the mechanism
of this digestive tract physiology support is discussed. The tea,
prepared with the green papaya leaf, promotes digestion and
aids in the treatment of ailments such as chronic indigestion,
overweight and obesity, arteriosclerosis, high blood pressure
and weakening of the heart (Mantok, 2005).
Antiseptic agent
The fresh, green papaya leaf is an antiseptic, whilst the brown,
dried papaya leaf is the best as a tonic and blood purifier
(Bonsu, 1999). The green unripe papaya has a therapeutic value
due to its antiseptic quality. It cleans the intestines from
bacteria, (only a healthy intestine is able to absorb vitamin and
minerals, especially vitamin B12) (Mantok, 2005).The yellow
papaya leaf is equally used as anti-anaemic agent while the
brown leaf is used as a body cleanser (Bonsu, 1999). Chewing
the seeds of ripe pawpaw fruit also helps to clear nasal
congestion (Kafaru, 1994).
Management of sickle cell anaemia
Folk medicine reportedly uses papaya as an herbal remedy for
the management of sickle cell anaemia. The results indicate that
the previously reported anti-sickling properties of papaya may
be due to the inherent antioxidant nutrient composition, thus
supporting the claims of the traditional healers and suggests a
possible correlation between the chemical composition of the
papaya plant and its uses in traditional medicine as an anti-
sickle cell anemia agent (Imaga et al., 2010). In addition,
Oduola et al. (2006) has described about the anti-sickling
activity of unripe papaya extracts that the anti-sickling and
reversal of sickling activities reside in the ethyl acetate fraction
that prevents the sickling of hemoglobin of the sickle cell
patients.
Anxiolytic and antioxidant activity
Papaya has been used in the Ethiopian traditional system of
medicine to relieve stress and other disease conditions.
Therefore a study was undertaken to evaluate the anxiolytic and
sedative effects of 80% ethanolic papaya pulp extract in mice.
The papaya pulp extract 100 mg/kg showed significant
anxiolytic activity without altering locomotor and sedative
effects and this study authenticated the traditional usage of
papaya as an anxiolytic medicinal plant (Kebebew and Shibeshi,
2013). Similarly, a study was designed to explore the
toxicological and antioxidant potential of dried C. papaya juice
in vitro and in vivo. In vivo examination was performed after
oral administration of dried papaya juice to rats for 2 weeks at
doses of 100, 200 and 400 mg/kg. Blood TBARS and FRAP
assays were used to determine the potential of the juice to act
against oxidative stress. The acute toxicity test (LD50)
demonstrated that papaya juice is not lethal up to a dose of
1500 mg/kg after oral administration and thus is considered
nontoxic. In treated groups, no sign of toxicity was observed. In
vitro evaluation of the antioxidant effects of papaya showed
that the highest antioxidant activity (80%) was observed with a
concentration of 17.6 mg/mL. This preliminary study indicates
the safety and antioxidative stress potential of the juice of
papaya, which was found to be comparable to the standard
antioxidant compound alpha-tocopherol (Mehdipour et al.,
2006). The study conducted by da Silva et al. (2010) further
supports the notion that papain, the compound isolated from the
latex of unripe C. papaya is a promising source of potential
antioxidant.
Management of heart diseases
Unripe pulp of C. papaya is rich in carbohydrate and starch
(Oloyede, 2005) and also contains cardenolides and saponins
that have medicinal value such as cardenolides used in the
treatment of congestive heart failure (Schneider and Wolfing,
2004). Carpaine, an alkaloid with an intensely bitter taste and a
strong depressant action on the heart, has been obtained mainly
from the leaves, fruit and seeds of papaya (Hornick et al., 1978).
Fig. 8. Papaya a gifted Nutraceutical
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Anticancer agent
Papaya leaf juice is consumed for its purported anti-cancer
activity by people living on the Gold Coast of Australia, with
some anecdotes of successful cases being reported in various
publications. Papaya leaf extracts have also been used for a
long time as an aboriginal remedy for various disorders,
including cancer and infectious diseases (Otsuki et al., 2010).
There have been anecdotes of patients with advanced cancers
achieving remission following consumption of tea extract made
from papaya leaves. Papaya plants produce natural compounds
(annonaceous acetogenins) in leaf, bark and twig tissues that
possess both highly anti-tumor and pesticidal properties
(McLanghlin et al., 1992). The papaya leaf tea or extract has a
reputation as a tumour-destroying agent (Last, 2008).
To examine the potential role of papaya in anti-cancer
therapy a study was conducted to exhibit the anti-tumour
activity of the aqueous extract of the leaves of the papaya
against various cancer cell lines, as well as its potential
immunomodulatory effects, and attempted to identify the active
components and observed significant growth inhibitory activity
of the papaya extract on tumor cell lines. Finally, the identified
active components of papaya extract are observed to inhibit
tumour cell growth and to stimulate anti-tumour effects (Otsuki
et al., 2010). In the leaves of papaya, components previously
reported to potentially have anti-tumour activity includes
tocopherol (Ching and Mohamed, 2001), lycopene (van
Breemen and Pajkovic, 2008), flavonoid(Miean and Mohamed,
2001), and enzylisothiocyanate (Basu and Haldar, 2008). A
recent review conducted by Nguyen et al. (2013) indicated that
to date no clinical or animal cancer studies were identified and
only seven in vitro cell-culture-based studies were reported;
these indicate that C. papaya extracts may alter the growth of
several types of cancer cell lines. Nevertheless, many studies
focused on specific compounds in papaya and reported
bioactivity including anticancer effects. This review
summarizes the results of extract-based or specific compound-
based investigations and emphasizes the aspects that warrant
future research to explore the bioactives in C. papaya for their
anticancer activities. These studies clearly suggest that the
papaya has a direct antitumor effect on various types of cancers,
and therefore, it could be useful in possible therapeutic
strategies in the fight against cancers.
Anthelmintic activity of papaya latex
In many of the resource-poor settings people could not afford to
procure the commercially available modem anthelmintic agents
(Gyuatt and Evans, 1992). As a result, one should not neglect
the fact that there is a long tradition of using medicinal plants,
some of which have been claimed, on empirical grounds, to
possess anthelmintic activities (Dharma, 1985; Perry, 1980).
One of the plants claimed to be effective against roundworms
in humans is the papaya tree. In Papaya-producing countries
the fruit is used as the drug for the treatment of parasitosis
(Stepek, 1999) and infected skin lesions (Starley, 1999).
Papaya seeds are used against intestinal parasites in humans
and farm animals in India (Lal et al., 1976), Central and South
America (Roig and Mesa, 1974) and elsewhere (Werner, 1992).
The extracts have been proven to be effective against
Caenorhabditis elegans and other helminths in vitro and, where
tested, in infected animals (Dar, 1965; Kermanshahi, 2001;
Krishnakumari and Majumder, 1960; Robinson, 1958). Papaya
latex has showed marked in vivo efficacy against the rodent
gastrointestinal nematode, Heligmosomoides polygyrus (Stepek,
1999).
In a recent experimental study, latex collected from young
papaya fruits were shown to possess anthelmintic activity
against patent Ascaridia galli infections in chickens (Mursof
and He, 1991). A study was conducted to evaluate the possible
anthelmintic activity of papaya latex against Heligmosoraoides
polygyrus in experimentally infected mice. The results suggest
a potential role of papaya latex as an anthelmintic against
patent intestinal nematodes of mammalian hosts (Satrija et al.,
1995).
Antitrichomonal activity
Trichomonas vaginalis causative agent of trichomoniasis is a
flagellate protozoan that parasitizes the human vagina, prostate
gland, and urethra. This parasitic infection has been associated
with vaginitis, cervicitis, urethritis, prostatitis, epididymitis,
cervical cancer, infertility, and pelvic inflammatory disease.
The most significant clinical signs of trichomoniasis are
vaginal or urethral discharge, foul-smelling discharge, dysuria,
pruritus, severe irritation, abdominal pain, and edema or
erythema. In pregnant women, trichomonads are implicated in
premature membrane rupture, premature labor, and in the
delivery of low-birth weight babies. In addition, T. vaginalis
could have an important role in the transmission and
acquisition of human immunodeficiency virus (Mundodi et al.,
2009; Schwebke and Burgess, 2004; Swygard et al., 2004).
In order to improve the current chemotherapy of T.
vaginalis infection, medicinal plants could be a source of new
anti-protozoal drugs with high activity, low toxicity and lower
price. Crude methanolic extracts from 22 Mexican medicinal
plants were screened for anti-trichomonal activity against T.
vaginalis. Among the plants tested C. papaya and Cocos
nucifera showed the best anti-trichomonal activity with IC50
values of 5.6 and 5.8 g/ml, respectively (Calzada et al., 2009).
Anti-dengue fever activity
Dengue fever is also known as breakbone fever and it is one of
the great infectious scourges of mankind. It is caused by any
one of four related viruses (Flaviviridae) and is transmitted
through the infective bite of the mosquitoes, Aedes aegypti and
Aedes albopictus. In the recent decades, it has become a major
international public health concern. It has been estimated that
over 2.5 billion (40%) of the world's population are at the risk
of dengue infection. The WHO estimates that there may be 50-
100 million cases worldwide every year. Before 1970, only
nine countries had experienced severe dengue epidemics.
However, now it is endemic in more than 100 countries in
Africa, the Americas, the Eastern Mediterranean, South-east
Asia and the Western Pacific region. Hence, it clearly shows
that dengue is emerging and resurging as a global public health
threat in a new changing environment, which is a matter of
grave concern, calling for the innovative tools as well as
approaches in terms of vector control, surveillance, and dengue
fever case management. Dengue fever is mainly combated by a
combination of vector control, personal protection and disease
management by drugs. However, at the moment there are no
specific antibiotics as well as potential reliable vaccine against
dengue virus (DENV). Therefore, identifying affordable
effective anti-dengue agent in terms of anti-dengue drugs is
extremely important and inevitable too.
Recent reports have claimed possible beneficial effects of C.
papaya leaf juice in treating patients with dengue viral
infections. As a result, a study was conducted Ranasinghe et al.
(2012) to evaluate the membrane stabilization potential of
papaya leaf extracts using an in vitro hemolytic assay. Two
milliliters of blood from healthy volunteers and patients with
serologically confirmed current dengue infection were freshly
collected and used in the assays. Fresh papaya leaves at three
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different maturity stages (immature, partly matured, and
matured) were cleaned with distilled water, crushed, and the
juice was extracted with 10 ml of cold distilled water.
Membrane stabilization properties were investigated with heat-
induced and hypotonicity-induced hemolysis assays. Extracts
of papaya leaves of all three maturity levels showed a
significant reduction in heat-induced hemolysis compared to
controls (p < 0.05). Papaya leaf extracts of all three maturity
levels showed more than 25% inhibition at a concentration of
37.5 μg/ml in vitro and could have a potential therapeutic effect
on dengue disease processes causing destabilization of
biological membranes.
In Pakistan a study was conducted by Ahmad et al. (2011)
to investigate the efficacy of C. papaya leaves extracts against
Dengue Fever Virus (DFV) in a 45 year old patient. The 25 ml
of aqueous extract was administered daily, twice i.e. morning
and evening for five consecutive days. Prior to the extract
administration the patients’ blood samples were analyzed for
Platelets count (PLT), White Blood Cells (WBC) and
Neutrophils (NEUT). Subsequently, following the
administration the blood samples were again re-examined and
found that there were significant rising of PLT, WBC and
NEUT. The blood sample analysis clearly demonstrates that the
aqueous extract of C. papaya leaves has the strong potential
activity against DFV. It is important to note that this is a
preliminary investigation and it needed further investigations
for the isolation and identification of responsible bio-active
molecules and their mode of action to combat dengue fever as
well as various other viral diseases very effectively in the future.
Antiplasmodial activity
It has been estimated that nearly half of the world’s population
is at the risk of contracting malaria with sub Saharan Africa
being the most risky area (Karunamoorthi, 2014). Malaria is
often referred to as a disease of poverty and a cause of poverty.
It is quite understandable that malaria is quite endemic in
nature in the poorest regions of the world (Karunamoorthi,
2012b). It imposes an enormous burden in terms of morbidity
and mortality in the tropical and subtropical regions of the
world, particularly Asian and sub-Saharan African countries.
Quite often the main victims are expectant mothers and
children under the age of five (Karunamoorthi et al., 2010a).
Besides, it is one of the major obstacle to socioeconomic
development as the main disease transmission seasons coincide
with peak agricultural and harvesting period (Karunamoorthi
and Bekele, 2009).
The existing malaria control intervention largely depends
on the front-line arsenals like effective case management with
artemisinin combination therapies (ACTs), distribution of long
lasting insecticide treated nets (LLINs) and selective
intradomicillary spraying (Karunamoorthi and Sabesan, 2013).
However, global-warming concomitant effects, insecticide
resistance, and drug resistance have fueled the insurgence and
resurgence of many vector-borne diseases, particularly malaria
(Karunamoorthi et al., 2010b; Karunamoorthi 2012c).
Consequently, current malaria control is facing serious
challenges to address the above cited issues by identifying the
alternative plant-based affordable, accessible potential
antimalarials (Karunamoorthi et al., 2013b), and in exploring
the risk-reduced pesticides or green pesticides to combat
malaria effectively (Karunamoorthi, 2012d). Since malaria is a
major public health issue in the resource-limited settings, where
there is a fragile health care system, it quite often fails to meet
the expectation of needy poor people. The existing potent
antimalarial ACTs has been often unaffordable, inaccessible
and the recent reports indicate the emergence of multi-drug
resistance strains against ACTs too (Karunamoorthi and
Tsehaye, et al., 2012). As a result, in order to address the
antimalarial drug resistance catastrophe, a keen interest has
been observed among the researches towards TSM to explore
the possibilities of identifying the new affordable, accessible
and potential antimalarial drugs from our age-old TSM.
Mature leaves of C. papaya are widely used to treat malaria
and splenomegaly while the fruit is often used against anaemia,
which can also be caused by malaria (Adjanohoun, 1996). The
petroleum ether extract of the seed rind of this species showed
a considerable antimalarial activity, with an IC50 of 15.19 µg/ml
(Bhat and Surolia, 2001). This clearly indicates that the papaya
seeds contain the highly active antiplasmodial
compounds. Moreover, Ngemenya et al. (2004) has also
recorded the antiplasmodial activity of the leaves and seeds
of C. papaya with IC50 of about 60 µg/ml. In Ethiopia,
Karunamoorthi and Tsehaye (2012) reported that the local
residents are consuming the powder of the papaya seeds by
mixing with honey orally as an antimalarial agent. A study was
carried out evaluate the antimalarial activity of the methanolic
seed extract of C. papaya on Plasmodium berghei infected
mice. The seed extract of C. papaya showed a significant
malaria parasitaemia suppressive activity (p ≤ 0.05). These
activities are dose dependent and comparable to those of
Chloroquine phosphate. The present finding justifies the
inclusion of the seeds of C. papaya in the treatment of malaria
by local herbalists. The seeds extract therefore, if well purified
and characterized may be used in treatment of very early
plasmodiasis as well as a good prophylactic drug in human.
This work is limited to animals, thus clinical trials in humans
are recommended particularly, when C. papaya seeds are non-
harmful/non toxic (Amazu et al., 2009).
Melariri et al. (2011) investigated the antiplasmodial
properties of crude extracts from C. papaya leaves to trace the
activity through bioassay guided fractionation. This study
demonstrated greater antiplasmodial activity of the crude ethyl
acetate extract of C. papaya leaves with an IC50 of 2.96/0.14
μg/ml when compared to the activity of the fractions and
isolated compounds. Yet the presence of alkaloids in the leaves
of papaya could be the rationale why it is often being
effectively administered as an anti-malarial agent (Ayoola and
Adeyeye, 2010). However, so far there is no comprehensive
report on the phyto-chemistry and mode of action of papaya
with reference to its antiplasmodial activity. Therefore, further
pharmacological and phytochemical investigations on papaya
are required to be warranted to authenticate the claims or
beliefs on the efficacy and safety concerns (Karunamoorthi and
Tsehaye et al., 2012).
Insecticidal agent
Vector control is a corner stone in the fight against vector-borne
diseases particularly malaria (Karunamoorthi, 2011).
Insecticides are considered to be a powerful weapon in order to
enhance the agricultural productivity and considerably to
improve the major public health indices too (Karunamoorthi et
al., 2012b). However, over the past six decades, insecticides are
playing the crucial role to contain the vector-borne diseases and
have saved hundreds of millions of lives every year. In the last
decade, we have attained a remarkable success to combat with
many arthropod-borne diseases particularly malaria. All credits
go to the combined effect of IRS, long-lasting insecticidal nets
(LLINs), and effective case management. However, now
malaria vector control is facing a serious challenge in terms of
insecticide resistance, particularly against pyrethroids
(Karunamoorthi and Sabesan, 2009).
Pyrethroid resistance is a potential threat to the global
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public health concern. It is largely due to the heavy reliance,
recurrent and inappropriate pyrethroid usage. Therefore, it has
to be addressed immediately to sustain the recent success of
vector control, unless it would become uncertain
(Karunamoorthi and Sabesan, 2013). It calls for the searching
of new insecticides with novel mode of action. As a result, it is
the hour to launch an extensive search to explore eco-friendly
biological materials for the control of insect pests, and we are
all just around the corner to reinstate the ubiquitous chemical of
concern by plant-based products in the insect control
(Karunamoorthi et al., 2008).
Over the centuries, even before the advent of modern
synthetic pesticides our ancestors completely depended upon
the usage of plant-derived products as a pesticidal agent against
various insects. At the moment, a renewed interest has been
observed to exploit the insecticidal control potentialities of
various plant-based products (Karunamoorthi et al., 2009). The
rationale behind the reawakened desire for searching the new
plant-based insecticides with novel mode of actions is not only
a part of new Integrated Pest Management (IPM) strategy, but it
also inhibits the development of resistance with the existing
chemical insecticides, It shall further reduce the heavy reliance
of chemical pesticides as well as their adverse impact on
human health and environment. In general, green
pesticides/risk reduced pesticides are target-specific and can be
non-toxic (Karunamoorthi, 2012d).
An investigation has been conducted to determine the
mosquito-larvicidal potential of ten Nigerian plantcrude
extracts against the fourth instar larvae of Anopheles gambiae.
The larvicidal activity (LA) expressed as % LA was
concentration and incubation-time dependent. The out of ten
plants at 5% w/v (12 and 24 h), only C. papaya and Dacryodes
edulis have demonstrated remarkable larvicidal activity of 40%
and 55% and 50% and 70%, respectively while the rest were
largely inactive. This investigation suggests a potential use of
papaya in the control of malaria vector mosquitoes (Oladimeji
et al., 2012). The methanolic leaf extract of C. papaya showed
lethal effects against the first- to fourth- instar larvae and pupae
of Culex quinquefasciatus , the LC50 value of I instar was 51.76
ppm, 2nd instar was 61.87 ppm, III instar was 74.07 ppm, and
IV instar was 82.18 ppm, and pupae was 440.65 ppm,
respectively (Kovendan et al., 2011).
Crude and solvent extracts of seed extract of C. papaya was
investigated for anti-mosquito potential, including larvicidal,
pupicidal and adulticidal, activities against Cx.
quinquefasciatus and An. stephensi, the vector of filariasis and
malaria, respectively. The mortality rate of 3rd larval instars of
Cx. quinquefasciatus and An. stephensi at 0.5% concentration
was significantly higher (P value - 0.05) than the mortality
rates at 0.1%, 0.2%, 0.3% and 0.4% concentrations of crude
extract. Among the solvent extracts, the petroleum ether extract
showed the highest mortality at 100 ppm with LC50 and LC90
values of 31.16 ppm and 341.86 ppm against Cx.
quinquefasciatus; 18.39 ppm and 250.76 ppm against An.
stephensi. Papaya plant extract exhibited a slightly pupicidal
potency with LC50 values of 86.53 ppm and 72.16 ppm against
Cx. quinquefasciatus and An. stephensi respectively (Rawani et
al., 2012).
Mosquito repellent activity
Repellents are playing the pivotal role whenever and wherever
other personal protection measures like ITNs are impossible or
impracticable (Karunamoorthi and Sabesan, 2010). Plants have
been used since ancient times to repel/kill blood-sucking
insects in the human history and even today, in many parts of
the world people are using plant substances for the same
(Karunamoorthi et al., 2008).Globally, numerous studies
evidently suggest that the traditionally used plant-based insect
repellents are promising and could potentially contain vectors
of the disease (Karunamoorthi et al., 2014). This appropriate
strategy affords for the opportunity to minimize chemical
repellents usage and the risks associated with the adverse side
effects (Karunamoorthi et al., 2010b). Water extracts of C.
papaya seeds repel various kinds of insects. The extracts
obtained by pressing the papaya roots destroy the nematodes in
soil and the extracts from the immature fruit controls termites
effectively (Buhner, 2000).
Crude and solvent extracts of seed extract of Carica
papaya was investigated for adulticidal, smoke toxicity and
repellent activities against Cx. quinquefasciatus and An.
stephensi. It showed repellency against the adult females of
both mosquito species with 78% and 92% protection
respectively. It also provided biting protection time of 4 h and 5
h respectively against Cx. quinquefasciatus and An. stephensi.
In adulticidal activity there is 70% and 63.3% death of adult
mosquito against Cx. quinquefasciatus and An. stephensi after
72 h. The smoke toxicity test showed that out of 200 adult
mosquitoes, 190 adult mosquitoes of Cx. quinquefasciatus and
186 mosquitoes of An. stephensi dropped down at the floor
after 5 h of smoke (Rawani et al., 2012).
A study was conducted to document the efficacies of
mosquito repellents from extracts of plants such as Capsicum
frutescens, C. papaya and Cyanodon dactylon, which are
traditionally known to repel mosquitoes. The results suggesting
that the distillates of the fruits of C. frutescens and C. papaya
were effective for 2.5 h, whilst the mixture of C. frutescens and
C. papaya was effective for 4 h. Whereas the mixture of C.
papaya and C. dactylon was effective for 2.5 h. Mixtures of
highly repellent extracts are observed to offer higher protection
against Aedes aegypti mosquitoes (Kazembe and Makusha,
2012). It is well-known that to-date, the scientific community
has tested over thousands of traditional repellents plants to
identify the potential plant-based insects/mosquitoes repellents.
These findings clearly suggesting that papaya extracts possess
remarkable larvicidal, pupicidal, adulticidal and repellent
activity against various species of vector mosquitoes. However,
further investigations are required to be warranted to elucidate
the responsible bio-active ingredients and their mode of
mechanism in the near future. There are many key challenges
and issues that lie ahead for the advancement of the ideal
commercial insect repellent from plant as a source
(Karunamoorthi, 2012e).
Genito-urinary infection
Dried and pulverized leaves are used for making tea; also the
leaf decoction is administered as a purgative for horses and
used for the treatment of genito-urinary system (Adebiyi et al.,
2002).
The contraceptive efficacy and reversibility
The oral administration of an aqueous suspension of the
powder of papaya seeds induces sterility in 40% of treated male
rats, without affecting the weight of the genital organs,
spermatogenesis, and the motility of the spermatozoa (Das,
1980). Chinoy et al. (1984) reported a complete loss of fertility
in albino rats and mice treated with aqueous extract of the seeds
of C. papaya i.m. at 0.5 mg and 5 mg/kg body wt./d for 7 d.
The papaya seed extract induce variable degree of responses
depending on dose, duration, and route of administration in
laboratory animals. In rabbits, dry seed powder of papaya
suspended in distilled water and administered orally resulted in
complete sterility in rats (Vyas and Jacob, 1984). Among the
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various extracts tested, it was reported that the chloroform
extract and partially purified fractions of the chloroform extract
were more effective in male rats (Lohiya and Goyal, 1992;
Lohiya et al., 1994a, b). The effects were reversible and
without appreciable changes in the toxicological profile.
An extensive investigation is being carried out in various
animal models with various extracts of the seeds of papaya, to
evaluate as a potential male contraceptive tool (Lohiya et al.,
1999).The contraceptive efficacy and reversibility of the
chloroform extract of the seeds of papaya in adult male rabbits
were investigated. Sperm concentration showed a gradual
decline, reached severe oligospermia (fewer than 20 million/ml)
after 75 d treatment, and attained uniform azoospermia after
120 d treatment. Sperm motility and viability were severely
affected after 45 d treatment and reached less than 1% after 75
d treatment. The morphology of the spermatozoa by scanning
electron microscopy revealed membrane damage in the
acrosome, bent midpiece, coiled tail, and detached head and tail.
Histology of the testis revealed arrest of spermatogenesis
beyond the level of spermatocytes. No toxicity was evident
from the haematology and serum biochemistry parameters. The
libido of the treated animals was unaffected and the fertility
rate was zero. The effects were comparable in both the dose
regimens (Groups II and III) and were restored to normal 45 d
after withdrawal of the treatment (Lohiya et al., 1999).
Goyal et al. (2010) conducted a study to authenticate
scientific documentation of the seeds of papaya being
traditionally used for contraception and to establish safety of
the methanol sub-fraction (MSF) of the seeds of papaya as a
male contraceptive following long term oral treatment. They
found that the long term daily oral administration of MSF
affects sperm parameters without adverse side effects and is
clinically safe as a male contraceptive. The seeds of papaya are
reported to possess emmenagogue, abortifacient and
antifertility properties (Chopra et al., 1958).
In trials with rats, daily oral doses of benzene and alcohol
extracts (20 mg/kg body weight (BW) for 30 days) did not
affect body or reproductive organ weights or adversely affect
liver or kidney function. However, aqueous extracts (1 mg/kg
BW for 7 or 15 days) and benzene extracts given orally to
female rats caused infertility and irregular oestrous cycles.
Male rats given ethanol seed extracts orally (10 or 50 mg/day
for 30, 60, or 90 days) or intramuscularly (0.1 or 1.0 mg/day
for 15 or 30 days) had decreased sperm motility. The oral doses
also decreased testis mass and sperm count. Studies with
aqueous seed extracts also decreased fertility in male rats. The
fertility of the male and female rats returned to normal within
60 days after the treatments were discontinued (Cornel
University, 2009). In addition to decreasing infertility, papain
might cause abortions shortly after conception. The papain
apparently dissolves a protein(s) responsible for adhering the
newly fertilized egg to the wall of the uterus (Cornel University,
2009).
Traditional uses of papaya
Papaya fruits, seeds, latex and extracts have been used
traditionally to treat various ailments in humans across the
world. According to the folk medicine, papaya latex can cure
dyspepsia and also applicable for external burns and scalds.
Seeds and fruits are excellent anti-amoebic (Okeniyi et al.,
2007). Dried and pulverized leaves are sold for making tea;
also the leaf decoction is administered as a purgative for horses
and used for the treatment of genetic-urinary system (Adebiyi
et al., 2002). Papain is popularly used as a chewing gum
additive and beer clarifier plus for a large number of additional
medical, cosmetic and industrial purposes.
Carapine, an alkaloid present in papaya, can be used as a
heart depressant, amoebicide and diuretic. The fruit and juice
are eaten for gastrointestinal ailments; a fresh leaf poultice is
used to treat sores. The fresh root with sugarcane alcohol can
be taken orally or as a massage to soothe rheumatism. A flower
decoction is taken orally for coughs, bronchitis, asthma and
chest colds. In some countries, the seeds are used as an
abortifacient and vermifuge (Orwa et al., 2009). Leaves have
been poultice into nervous pains, elephantoid growths and it
has been smoked for asthma relief among tropical tribal
communities. The stem and bark may be used in rope
production (Rawani et al., 2012).
Wound healing properties
Wound healing, or wound repair, is the body’s natural process
of regenerating dermal and epidermal tissue. The sequence of
events that repairs the damage is categorized into separate
inflammatory, proliferative and maturation phases (Diegelmann
and Evans, 2004). Extracts from the epicarp of green papaya
used in this experiment have been shown to be beneficial for
treatment of wounds. This finding is consistent with the
observation that topical application of the unripe fruit papaya
promotes desloughing, granulation and healing and reduced
odor in chronic skin ulcers (Hewitt et al., 2000). Recent study
conducted by Anuar et al. (2008) also has confirmed about the
ripe fruits improves wound healing property. Topical treatment
of mush pulp of papaya containing papain and chymopapain for
pediatric infected burns was effective for desloughing necrotic
tissue, preventing infection and roviding a granulating wound
(Starley, 1999).
Meat tenderizer and other uses
Green papayas are sometimes cooked as a vegetable; they also
can be pickled or candied. Papain, the protein-splitting enzyme
found in green papaya, is extracted and sold commercially as a
meat tenderizing sauce. This tenderizing effect can also be
achieved by laying slices of green papaya or green papaya skin
on the meat and allowing it to stand for several hours (Low and
Maretzki, 1982). Milky juice of unripe fruits is used as a
cosmetic to remove freckles and other blemishes from the skin.
The seeds have a mild, peppery taste and may be ground and
used in place of pepper in salad dressings or in recipes calling
for, mustard seed. If eaten in large quantities may cause
diarrhea due to the presence of the benzylisothiocyanate (BITC)
in papaya seeds (Low and Maretzki, 1982). The seeds are also
used as emmenagogue, thirst quenchers, carminatives or for
bites and stings of poisonous insects (Wiart, 2006). The papaya
has been traditionally used to treat several skin diseases. In
Cambodia, Laos and Vietnam, latex is used to treat eczema and
psoriasis (Amenta et al., 2000).
Toxicological profile
Papaya leaves have been used in ethnomedicine for the
treatment of various diseases and illness. Despite its benefits,
very few studies on their potential toxicity have been described.
A study was carried out to characterize the chemical
composition of the leaf extract from 'Sekaki' C. papaya cultivar
by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute
oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and
2 g/kg by examining the general behavior, clinical signs,
hematological parameters, serum biochemistry and
histopathology changes. A total of twelve compounds
consisting of one piperidine alkaloid, two organic acids, six
malic acid derivatives, and four flavonol glycosides were
characterized or tentatively identified in the C. papaya leaf
extract. In the sub-acute study, the C. papaya extract did not
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2014 / Volume 4 / Issue 1 / e2
cause mortality nor were treatment-related changes in body
weight, food intake, water level, and hematological parameters
observed between treatment and control groups.
Histopathological examination of all organs including liver did
not reveal morphological alteration. Other parameters showed
non-significant differences between treatment and control
groups. The results suggest that C. papaya leaf extract at a dose
up to fourteen times the levels employed in practical use in
traditional medicine in Malaysia could be considered safe as a
medicinal agent (Afzan et al., 2012).
Papaya seed preparations are used in traditional medicine to
expel intestinal worms in human and ruminants. In the study,
an ethanol extract of papaya seeds (EEPS; 0.1 - 6.4 mg/ml)
caused concentration-dependent inhibition of jejunal
contractions in contrast to corresponding concentrations of
DMSO (solvent control). The inhibitory effect of EEPS on
jejunal contractions was significantly irreversible. Previous
studies have indicated that benzyl isothiocyanate (BITC) is the
main bioactive compound responsible for the anthelmintic
activity of papaya seeds. In the present study, standard BITC
(0.01 - 0.64 mmol/l) also caused significant irreversible
inhibition of jejunal contractions. Cryosections of the jejunum
showed marked morphological damage of the segments treated
with BITC in contrast to DMSO-treated segments. EEPS-
induced jejunal damage was, however, less marked. These
results indicate that papaya seed extract and BITC, its principal
bioactive constituent are capable of weakening the contractile
capability of rabbit isolated jejunum. It is thus envisaged that at
the toxic level that will be needed to kill and expel intestinal
worms in vivo, BITC may also cause impairment of intestinal
functions (Adebiyi and Adaikan, 2005).
A study was conducted to investigate the acute toxicity of
papaya leaf extract on Sprague Dawley rats at a dose of 2000
mg/kg body weight (BW). Sighting study was conducted in a
stepwise procedure using the fixed doses of 5, 50, 300, and
2000 mg/kg The single oral dose of the papaya leaf extract did
not produce mortality or significant changes in the body weight,
food and water consumption. The relative weights of the
internal organs were normal. However, hemoglobin (HGB),
hematocrit (HCT), red blood cell (RBC) and total protein were
significantly increase indicating dehydration. Apart from
triglyceride, other biochemistry parameters demonstrated no
significant changes as compared to the control. (Halim et al.,
2011). Melissa et al. (2008) reported that the male and female
Wistar rats (N = 56) received diets containing transgenic or
non-transgenic papayas at twice the equivalent of the average
daily human consumption of fresh papayas. No adverse effects
on animal behaviour or differences in body weight and organ
weight between control and treated groups were observed
during the study. Necropsy at the end of the study indicated that
neither pathological nor histopathological abnormalities were
present in the liver and kidneys of rats in the control and treated
groups. The present scrutiny clearly found that the exception of
infertility, the literature reviewed did not indicate any adverse
reactions from the consumption of papaya fruit, latex, or
extracts. However, the leaves and roots of papaya contain
cyangenic glucosides which form cyanide. The leaves also
contain tannins. Both of these compounds, at high
concentrations, can cause adverse reactions. Also, inhaling
papaya powder (high in the enzymes papain and chymopapain),
can induce allergies (Cornel University, 2009).
Consuming papaya fruit is it safe during pregnancy?
In fact, this is one of the foremost questions around the world
people keep on questioning to obtain an accurate answer due to
some of the popular belief in many countries. Through this
scrutiny, the author would like to convey to the people bit
cautiously by citing a few earlier scientific reports that the
consumption of ripe papaya fruits during pregnancy causes no
risk. However, the ingestion of unripe and semi-ripe papaya
could be unsafe during pregnancy (Adebiyi et al., 2002).It
induces miscarriage in susceptible pregnant women. It is purely
the unripe fruit contains much more latex compared to the ripe
papaya. Adaikan and Adebiyi (2004) found that crude papaya
latex contains papain and chymopapain. They are strong uterine
contractants and cause uncontrolled uterine contractions
leading to abortion (Cherian, 2000).
CONCLUSIONS
Indeed, papaya is an ancient herbal medicinal plant. It is
nutritious and medicinal values well-known worldwide. In the
ethnomedicine it has been used as a nutraceutical to
treat/prevent wide range of diseases/disorders, including cancer.
Besides, it also has traditionally been used for various purposes
like meat tenderizer, contraception, medicine acne, menstrual
pain reducer, and appetite enhancer. The findings of the present
scrutiny clearly suggest that the papaya plant parts possess
powerful anti-plasmodial, anti-trichochramal, anti-trichomonal,
anti-dengue, and anti-cancer properties. It also exhibits its
potentiality as antiseptic, anti-parasitic, anti inflammatory, anti-
diabetic, contraceptive activity, and management of sickle cell
anemia and heart diseases, indigestions and dysfunctions in the
gastrointestinal tract. However, the modes of actions are not
clearly understood, therefore further clinical studies have to be
undertaken to delineate about the mechanisms.
This scrutiny also clearly suggests papaya as one of the
excellent Nutraceutical Plants. Therefore enormous public
health awareness campaigns must be instigated through printed
and electronic media about the new linking of food and optimal
health. Furthermore, the policy makers, physicians, public
health experts and nutriounist must advocate the optimal
benefits of papaya as a food or as a quasi drug to prevent/treat
various ailments through social media. Besides, currently the
conservation and sustainable utilization of edible plant and
their biodiversity for the food production and nutraceutical is a
matter of grave concern. Therefore, appropriate precautionary
measures must be taken for the preservation and cultivation of
papaya tree as it is an excellent choice in terms of socio-
economic perspective. The author hopes that it could be
extremely helpful for the further enhancement of traditional
system of medicine in the developing world too.
ACKNOWLEDGEMENTS
I sincerely would like to thank Mrs. L. Melita for her sincere
assistance in editing this manuscript. I am extremely grateful to
the Mr. Rajan and Mrs. Florance Rajan for describing their
personal experience about the custom and practices of papaya
in the Indian system of medicine. I also would like to
acknowledge my wife Mrs. K. Dhavamani and my kids Mr.
Rohith and Ms. Mathivathani for their valuable support,
without their contribution, this study would have been
impossible. My last but not least heartfelt thanks go to our
colleagues from the School of Environmental Health Science,
Faculty of Public Health, Jimma University, Jimma, Ethiopia,
for their kind support and cooperation.
CONFLICT OF INTEREST
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2014 / Volume 4 / Issue 1 / e2
None to declare.
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