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The surprising health benefits of papaya seeds: A review

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 Journal of Pharmacognosy and Phytochemistry 2017; 6(1): 424-429

E-ISSN: 2278-4136
P-ISSN: 2349-8234 The surprising health benefits of papaya seeds: A
JPP 2017; 6(1): 424-429
Received: 24-11-2016 review
Accepted: 25-12-2016

Dr. Neethu S Kumar

Assistant Professor, Post
Dr. Neethu S Kumar, Sreeja Devi PS
Graduate Department and
Research Centre of Botany, Abstract
Mahatma Gandhi College, The study mainly focused on the secret behind the papaya seed against cancer. Papaya (Carica papaya
Thiruvananthapuram, Linn.) is well known for its exceptional nutritional and medicinal properties throughout the world. The
Kerala, India whole plant including its fruit, leaves, seed, root, bark, juice and latex obtain from papaya plant used as
nutritionally, medicinally and for various other purposes. A papaya in vitro study shows that it will treat
Sreeja Devi PS
many cancer cell line and papaya physiochemical having anticancer activities. Papaya is rich in enzyme
Post Graduate and Research
Centre, Department of Botany,
papain which is effective against cancer. Papain breaks down the fibrin cancer cell wall and protein into
Mahatma Gandhi College, amino acid form. Other than papain it also contain lycopene which highly reactive towards oxygen and
Kesavadasapuram, free radical. Isothiocyanate contained in papaya seed, work well for colon, breast, lung, leukemia and
Thiruvananthapuram, Kerala, prostrate cancer. These enzymes capable of inhibiting both formation and development of cancer cell.
India
Keywords: Papain, Lycopene, anticancer

1. Introduction
Papaya belongs to a small family caricaceae having four genera in world. The genus carica L.
is represented by four species in India, of which Carica papaya L. is the most widely
cultivated and the best-known species (Jean et al., 2011) [24]. It is commonly known as Papaya
Melon tree, Pawpaw or Papau, Kapaya, Lapaya, Papyas, Papye, Tapayas, Fan mu gua, papita,
arand- kharpuja, papayabaum and papaya (Bhattachrjee, 2001) [10]. The taxonomical
classification includes Kingdom (Plantae), Order (Brassicales), Family (Caricaceae), Genus
(Carica) and Species (papaya). Papaya is probably originated in southern Mexico and Costa
Rica, subsequently got introduced in Australia, Hawaii, Philippines, Sri Lanka, South Africa,
India and all tropical and subtropical regions. It is growing both commercially and in home
garden (Marotta et al., 2006) [32]. A study conducted by University of Florida researchers Nam
Dang and colleagues in Japan has documented papaya’s powerful anticancer properties and its
impact on numerous lab-grown-tumors.
The papaya seed contain fatty acids, crude protein, crude fibre, papaya oil, carpaine, caricin,
glucotropaeolin, benzyl glucosinolates, benzyl Isothiocyanate, benzyl thiourea, hentriacontane,
ß-sitostrol, caressing and an enzyme myrosin. The seeds and the pulp of Carica papaya
contain benzyl glucosinolate which can be hydrolyzed by myrosinase to produce benzyl
isothiocyanate. Seed extracts have profound bactericidal activity. The seeds of unripe fruits are
rich in benzyl isothiocyanate, a sulphur containing chemical that has been reported to be an
effective germicide and insecticide. These substances are important for plant natural defense
mechanisms (El Moussaoui et al., 2001) [16]. Medicinal uses of papaya seed are carminative,
anti-fertility agent in males, counter irritant, as a paste in the treatment of ringworm, psoriasis,
emmenagogue, vermifuge, liver cirrhosis and abortifacient. Seed juice is used for bleeding
piles, enlarged liver and pectoral properties. Seed paste is used as anthelmintic, stimulation of
menstruation or abortion.
Carica papaya seeds were approved and confirmed in some studies for their effective
anthelmintic properties against nematodes found in animals (Chota A., 2010) [13]. Chinoy et
al., (2006) [12] proved the anti-fertility, anti-implantation and abortifacient properties of
extracts from papaya seeds. It has been established in males that the seeds of C. papaya are
Correspondence
potential anti-fertility drugs (Lohiya et al., 2005) [30]. Pawpaw seeds are used to produce an
Dr. Neethu S Kumar indigenous Nigerian food condiment called ‘daddawa’, the Hausa word for a fermented food
Assistant Professor, Post condiment (Dakare, 2004) [15]. Fermented seeds have no effects on litters of rats (Abdulazeez
Graduate Department and et al., 2009) [1], whereas, those effects were apparent when the unfermented extract was
Research Centre of Botany, administered (Abdulazeez, 2008) [2]. Anthelmintic activity of papaya seed has been
Mahatma Gandhi College,
Thiruvananthapuram,
predominantly attributed to carpaine (an alkaloid) and carpasemine (later identified as benzyl
Kerala, India thiourea). Carpaine has an intensively bitter taste and a strong depressant action on health.

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Journal of Pharmacognosy and Phytochemistry

It is present not only in papaya fruit and seed but also in its by University of Florida researchers Nam Dang and
leaves. Benzyl isothiocyanate (BITC), the main bioactive colleagues in Japan has documented papaya’s powerful
compound in C. papaya seeds (Kermanshai et al., 2001) [25] anticancer properties and impact numerous lab-grown-tumors.
has been shown to be responsible for the anti-fertility effect Another important use of the papaya seed could prevent or
(Adebiyi et al., 2003) [4]. BITC is capable of damaging the possibly even treat food poisoning. The seeds of papaya are
endometrium, making the uterus non-receptive and, thus, believed to have strong anti-bacterial and anti-inflammatory
affecting adversely the implantation (Adebiyi et al., 2003) [4]. effect on our digestive system. Studies have shown that an
Seeds are also a rich source of amino acids; scented oil was extract made from papaya seed is effective in killing E.coli,
extracted, used in treatment of sickle cell disease and Salmonella, Staphylococus and other dangerous bacterial
poisoning related disorders (Saran and Choudhary, 2013) infections. There are even reports of using papaya seeds to
[45,46]
. Papain is used in food processing to tenderize meat, successfully treating viral infections such as Dengue fever in
clarify beer and juice, produce chewing gum, coagulate milk, parts of Central America like Costa Rica.
prepare cereals, and produce pet food, also to treat wool and
silk before dying, de-hair hides before tanning, adjunct in 2. Anti-amoebic activity
rubber manufacturing and proteolytic enzymes (papain and The study suggested that the cold macerated aqueous extract
chymopapain). Papaya seeds are rich source of amino acids of matured papaya seeds (100 µ/mL) showed significant anti-
especially in the sarcotesta. A yellow to brown, faintly amoebic activity against Entamoeba histolytica.
scented oil was extracted from the sundried, powdered seeds
of unripe papayas at the Central Food Technological Research 3. Anti-ulcer activity
Institute, Mysore, India. White seeds yielded 16.1% and black Aqueous seed extract of C. papaya at the dose of 50 mg/ kg
seeds 26.8% and it was suggested that the oil might have and 100 mg/kg against alcohol induced acute gastric damage
edible and industrial uses. Air dried papaya seeds with honey and blood oxidative stress in rats. The gastric acidity was
showed significant effect on human intestinal parasites significantly reduced in rats treated with 100 mg/kg of the
without significant side effect. Consumption of papaya seed is extract.
cheap, natural, harmless, readily available, mono-therapeutic 4. Anthelmintic
and prevent against intestinal parasitosis especially in tropical The dried papaya seeds gives as elixir with honey have shown
communities. significant effect on the human intestinal parasites, without
Under diverse agro-climatic conditions of North Bihar, the significant side effects. Benzylisothiocynate, present in seeds
autumn sown crop is best suited for seed production (Ram and is the chief anthelmintic.
Ray, 1992; Singh et al., 2010) [42, 48]. Quality seed production
suffer from several limiting factors including physiological 5. Effect on smooth muscles
disorders. Different nutrient deficiencies of boron, zinc and Ethanol extract of papaya seeds at 0.1-6.4 mg/mL showed
sulphur and environmental stresses cause several concentration dependent inhibition of jejunam contraction and
physiological disorders such as bumpy fruit which may lead found significantly irreversible. Thus the extract is capable of
to deformed/discolored seeds. Discolored seeds, vivipary weakening the contractile capability of isolated rabbit
seeds (Saha, 2007; Saran et al., 2013a) [44] and white seeds jejunam.
(disturbed sarcotesta) were identified as new physiological
disorders of papaya under diverse agro-climatic conditions of 6. Administration dependent antioxidant effect
India. During seed development period, proper temperature Seeds are the less exploited part thus this study is aimed at
also plays an important role. Keeping a fore-mentioned facts assessing the antioxidant activities of the C. papaya seeds
in mind, the present study was conducted on the varietal water extract against hydrogen peroxide (H2O2) oxidative
screening for bumpiness; morphology and economics of stress in human skin Detroit 550 fibroblasts. C. papaya seeds
bumpy fruits, deformed/discolored seeds, vivipary and white water extract is not toxic and acts as a potent free radical
seeds (disturbed sarcotesta) and relationship between scavenger, providing protection to Detroit 550 fibroblasts that
temperature and disorders (deformed seed and vivipary). underwent H2O2 oxidative stress. Study show that (1) the
Increasing anecdotal reports of its effects in cancer treatment maximum protective effect is achieved by the simultaneous
and prevention, with many successful cases, have warranted administration of the extract with 1 mmol/L H 2O2; (2) the
that these pharmacological properties be scientifically extract in presence of an oxidative stress does not increase
validated. A bibliographic search was conducted using the catalase activity and prevents the release of cytochrome C and
key words "papaya", "anticancer", and "antitumor" along with the inner mitochondrial transmembrane potential loss; (3) the
cross-referencing. No clinical or animal cancer studies were extract is more efficient than vitamin C to hamper the
identified and only seven in vitro cell-culture-based studies oxidative damage; (4) the purified subtractions of the seeds
were reported; these indicate that C. papaya extracts may alter water extract exert the same antioxidant effect of whole
the growth of several types of cancer cell lines. However, extract. In conclusion, C. papaya seed water extract is
many studies focused on specific compounds in papaya and potentially useful for protection against oxidative stress.
reported bioactivity including anticancer effects. This review
summarizes the results of extract-based or specific compound- 7. Immuno- modulatory activity
based investigations and emphasizes the aspects that warrant Chemical constituents of the C. papaya seed extract and its
future research to explore the bioactives in C. papaya for their bioactive fraction were examined in vitro using lymphocyte
anticancer activities. proliferation assays and complement-mediated haemolytic
According to the Journal of Ethno pharmacology published on assay.
the 17th of February, 2010, international doctors and
researchers from US and Japan have discovered that enzymes 8. Selected studies on pharmaceutical application of
found in Papaya Leaf Tea have dramatic cancer-fighting Carica papaya on laboratory animals
properties against a broad range of tumors. A study conducted The effects of Carica papaya on laboratory animals have been
reported as remarkable antifertility natural medicine
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Journal of Pharmacognosy and Phytochemistry

(Owoyele et al., 2008 & Lohiya et al., 2006) [37, 29]. Treating for its toxicity (Halim et al., 2011) [21]. In the study, Sprague
rats with papaya extract in a dose of 200 mg/kg/day for Dawley rats received fixed doses of 5, 50, 300 and 2000
periods of 1 and 8 weeks revealed pronounced hypertrophy in mg/kg of the extract and observed for 14 days. The given
sperm characteristics and its ultra-structure. Rats treated with doses even at the higher level (2000 mg/kg) did not produce
a lower dose of 50 mg/kg showed mild hypertrophy and mortality or significant changes in body weight or food and
hyperplasia effects in the mentioned characteristics. However, water consumption. The investigated rats did not show signs
gradual degeneration of the Sertoli cells, Leydig cells of toxicity and no deaths were observed. In addition, normal
germinal epithelium and germ cells were also been reported relative weights of the internal organs were observed.
(Manivannan et al., 2009) [31]. These findings were strongly However, significant increases in hemoglobin (HGB),
supported by other studies in which rats were given oral doses hematocrit (HCT), red blood cell (RBC) and total protein
of 50, 100, 250, and 500 mg/kg methanolic extract of C. were recorded indicating dehydration.
papaya seeds for 28– and 90–day periods (Lohiya et al.,
2006) [29]. It was found that in the rats treated with doses of 10. Studies on morphological and quantitative traits
50, 100 mg/kg of the extract the density of the sperm The observations were recorded from December, 2008 to
decreased whereas in the rats treated with the dose of 500 May, 2013. The average monthly temperature was recorded
mg/kg levels for the same period, the interval total sperm from IARI RS Pusa observatory. Morphological observations
motility was inhibited. Similar findings were reported in were recorded for fruit surface, seed attachment, seed color,
dose–dependent study in which suppression of aqueous C. seed surface, sarcotesta, removal of sarcotesta and vivipary in
papaya seed extract on sperm motility in mice was both varieties namely, Pusa Dwarf and Pune Selection-3. The
investigated and revealed that with high dosages of the fruits of Pusa Dwarf were observed with vivipary and
extract, decrease in both sperm count and viability were morphological observation for fruit surface, seed attachment,
observed (Verma et al., 2006) [58]. seed color, seed surface, seed size, sarcotesta and removal of
Aqueous extract of C. papaya seeds at doses of 100–400 sarcotesta during fruit harvesting (initia-tion of colour turning
mg/kg/day was investigated for its effects on hypolipidemic, stage) and seed extraction. The data were also recorded on the
cardioprotective parameters in normal male Wistar rats for 30 total number of seeds/fruit, number of normal seeds/fruit,
days (Adeneye et al., 2009) [5]. Three groups of rats were number of deformed seeds/fruit, white seeds/fruit, vivipary
orally administered either with extract of Carica papaya seed seeds/fruit, deformed seeds (%), seed harvest (%) and
at doses of 100, 200, and 400 mg/kg/day of the extract or 0.1 economic losses (Rs/ha) in Pusa Dwarf at seed crop
mg/kg/day of glibenclamide or 10 ml/kg/day of distilled water harvesting (December to May) due to deformed seed disorder
(control) for a period of 30 days. The results showed that in autumn crop. Each fruit was cut into two equal halves for
Carica papaya extract significantly (p<0.05) lowered the total observing the incidence. The deformed/discolored seeds were
cholesterol, serum triglyceride, fasting blood glucose and recorded by counting the seeds in different categories. An
significantly (p<0.05) reduced the density of lipoprotein economic loss was estimated by calculating the seed yield per
cholesterol in a dose dependent manner compared to the unit area in kilograms. Loss was estimated by observing seed
untreated control rats. A single oral dose at 2,000 mg/kg or harvest (normal and deformed percent) in particular months
5,000 mg/kg of methanolic and aqueous extracts of whole and multiplied by our sale price (at Rs. 40,000/kg).
unripe extract of Carica papaya seeds were tested for their Relationship between average monthly temperatures, time of
toxic effects in rats and they did not elicit signs of toxicity in fruit harvest and seed disorders, namely, deformed seed and
the treated animals (Ezike et al., 2009) [17]. This study was in vivipary seeds from December to May were shown during the
a good agreement with the previous investigated study study years.
(Lohiya et al., 2006) [29]. It was also found that rats orally
administrated with methanolic extract of Carica papaya seeds 11. The cytotoxic effect of C. papaya extract has been
daily for long term affected sperm parameters of the rats such tested in various cancer cell lines in vitro studies
as motility, viability and count (Goyal et al., 2010) [19]. summarized in table
Recently, extract of Carica papaya leaves was investigated

Cancer Cell
Treatment Result Reference
Line
Acute n-hexane extract of papaya Extract of seed: Dose dependently inhibited the superoxide
promyelotic seed or pulp (0.1– 100 generation (IC50 = 10 _g/mL) and the viability of cells Nakamura et
leukemia HL-60 _g/mL),Pure benzyl (IC50 = 20 _g/mL), comparable to that of pure benzyl al., 2006 [35]
cells isothiocyanate (10 _M) isothiocyanate. Extract pulp had no effects at 100g/mL

9. Phytochemicals in C. papaya with Reported Anticancer three groups of bioactive compounds-phenolics, Carotenoids,
Activities and glucosinolate-have attracted considerable interest in
Carica papaya contains a broad spectrum of phytochemicals anticancer studies. Pure compounds of these three groups
including enzymes (in the latex), Carotenoids (in fruits and have been extensively researched in vivo and in vitro studies
seeds), alkaloids (in leaves), phenolics (in fruits, leaves, and on many types of cell lines for their potential effects in cancer
shoots), glucosinolate (in seeds and fruits) (Krishna et al., treatment and prevention. These bio actives act via multiple
2008; Parle et al., 2011) [27, 40]. Some important mechanisms such as cancer cell signalling, proliferation,
phytochemicals found in C. papaya are Lycopene, apoptosis, migration, invasion, as well as angiogenesis and
Betacarotinoid, Benzyl isothiocyanate, Betacryptoxanthin, carcinogen elimination (Huang et al., 2009; Zhang et al.,
Benzylglucosinolate, chlorogenic acid, caffeic acid, 2004; Thornalley et al., 2002; Nakamura et al., 2006; Wu et
protocatechuic acid, Quercetin etc. Among more than 5000 al., 2009; Navarro et al., 2011; Wahle et al., 2011; Soobrattee
compounds from plants that have been identified to be et al., 2006; Tanaka et al., 2012; Van Breemen et al., 2011)
associated with anticancer properties (Huang et al., 2009) [23], [23, 62, 52, 35, 60, 36, 59, 49, 51, 57]
to exhibit in vitro and in vivo
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Journal of Pharmacognosy and Phytochemistry

anticancer activities. mechanisms (Barbara, October-2008) [8]. Researchers in Japan

clarified the mechanisms of action in a type of isothiocyanate
12. Papaya is Rich Source of Enzyme Papain which is found in papaya known as BITC. That underlies the
Effective against Cancer relationship between cell cycle regulation and appropriate cell
Papain is an endolytic plant cysteine protease enzyme which death. When cancerous cells die on schedule, they are no
is isolated from papaya (Carica papaya L.). It preferentially longer a problem. The researchers established that BITC
cleaves peptide bonds involving basic amino acids, exerted cancer cell killing effects that were greater in the
particularly arginine, lysine and residues following proliferating cells than in the quiescent cells. Cancer cells that
phenylalanine. (Menard et al., 1990) [33] The unique structure are proliferating are much more dangerous than cancer cells
of papain gives its functionality that helps to understand how that are in a state of dormancy (Barbara, 2009) [9].
this proteolytic enzyme works and it’s useful for a variety of
purposes. (Carica papaya L.). 16. Conclusion
Many cancer cells having a protective coating of fibrin. That Carica papaya is an important and promising natural
is why they go undetected for many months and years. Papain medicinal plant which could be utilized in several
breaks down that fibrin coat of cancer cell wall. So ultimately pharmaceutical and medical applications because of its
it helps diagnose cancer cells. effectiveness, availability and safety. The papaya plant has
been touted by traditional hearlers for counties as source of
13. Mechanism of Functions of Papain powerful medicine. Slice open a papaya and see hundreds of
The mechanism in which the function of papain is made shiny black seeds that all need to get there start in life from
possible is through the cysteine-25 portion of the triad in the the nutrition found in the fruit. Papaya promotes immune
active site that attacks the carbonyl carbon in the backbone of system. Papaya is potent cancer fighter that is highly effective
the peptide chain freeing the amino terminal portion. As this against hormone related to cancer as well as other cancer.
occurs throughout the peptide chains of the protein, the Papaya can stop the growth of cancer cell, halt metastasis and
protein breaks apart. The mechanism by which it breaks normalize cell cycle. Fruit and seed disorders in papaya cause
peptide bonds involves deprotonation of Cys-25 by His-159. great economic losses in seed production during autumn sown
Asparagine-175 helps to orient the imidazole ring of His-159 crop. We observed that Pune Selection-3 and Pusa Dwarf
to allow this deprotonation to take place. Although far apart were the most susceptible germplasm lines for bumpy fruit
within the chain, these three amino acids are in close and deformed seed disorders, while vivipary and white seeds
proximity due to the folding structure. It is though these three (disturbed sarcotesta) are a serious economic problem only in
amino acids working together in the active site that provides Pusa Dwarf. The challenges that Indian Agriculture faces in
this enzyme with its unique functions. Cys-25 then performs a the coming years remain enormous. The seed production in
nucleophilic attack on the carbonyl carbon of a peptide papaya with 100% genetic purity is difficult because of
backbone. (Menard et al., 1990; Tsuge et al., 1999) [33, 55] In dioecious nature of the plant. Therefore, the seed should be
the active site of papain, Cys -25 and His -159 are thought to produced either strictly under controlled condition or in an
be catalytically active as a thiolate imidazolium ion pair. isolated area.
Papain can be efficiently inhibited by peptidyl or non-peptidyl
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