ISSN: 0973-7510

E-ISSN: 2581-690X

Open Access
P. Sankarganesh1,2, Baby Joseph1, A Ganesh Kumar2 , S. Illanjiam2 and T Srinivasan2
1Centre for Research and Consultancy, Hindustan Institute of Technology and Science, Padur-603103, Chennai, Tamil Nadu, India.
2Department of Microbiology, School of Sciences, Hindustan College of Arts & Science, Padur-603103, Chennai, Tamil Nadu, India.
J Pure Appl Microbiol. 2018;12(2):751-756
https://doi.org/10.22207/JPAM.12.2.35 | © The Author(s). 2018
Received: 10/03/2018 | Accepted: 15/04/2018 | Published: 30/06/2018
Abstract

Carica papaya L. leaves contain potent secondary metabolites, such as alkaloids, phenolics, flavonoids, saponin, tannins, glycosides, and other crucial phytochemicals. The leaf is a source of several vitamins conferring it an anti-oxidant property. The leaf is also rich in dietary minerals and essential fatty acid. The fresh leaf extracts are used as a possible remedy for dengue viral infections in Asian countries. This review compiles the knowledge about the physiochemicals, phytochemicals, and biochemicals of Carica papaya L. leaves. This includes the identified chemical structures of alkaloids, phenolic, flavonoids, linoleic, and linolenicacids. Additionally, it covers up-to-date information on in-vitro anti-cancer and anti-gout and in-vivo anti-microbial properties, anti-oxidant, anti-sickling, hepatoprotective, hypolipidemic, hypoglycemic, and anti-gout effects.

Keywords

Fresh Leaves, Phytochemicals, Dietary Minerals, Vitamins, Anti-oxidant and bio-activity

Introduction

Carica papaya L. is commonly known as pawpaw tree. It is a nutraceutical plant.  All plant parts have vital immunostimulative and antioxidant effects.  The Indian traditional medicinal system prescribes its leaf extract to control dengue viral infections.  In other Asian countries, it is also used as a remedy for the same1.  The leaf contains a mixture of chemicals, which can be described broadly as physiochemical, phytochemicals and biochemicals.

Physiochemicals
The physiochemical nature of the dried leaf has following contents in % w/w:  Total Ash (17.4), Acid insoluble ash (13.3), Water soluble ash (3.25), Sulfated ash (27.05), Ethanol soluble extractive (8.4), Water-soluble extractive (17.7), Moisture content (5.70), Crude fat (2.8+0.3), Crude fiber (23+0.1), Crude protein (29.5+0.1), and Carbohydrate (35.9+0.3)2.

Phytochemicals
It contains alkaloids, phenols, flavonoids, saponin, tannins, and glycosides. They could be described as follows:

Alkaloids
The significant phytochemicals of Carica papaya L. leave are bitter tasting alkaloids (1,300–1,500 ppm).  It is in the form of carpaine (150–4,000 ppm) (Figure 1), pseudocarpaines, macrocyclic piperidine, dehydrocarpaine I and II (1000 ppm), and nicotine (102.8 ppm)3.

Fig. 1. Structure of carpaine (-13, 26-dimethyl-2, 15-dioxa-12, 25-diazatricyclotriacontane-3, 16-dione)

Carpaine
Its molecular formula is C28H50N2O4 (Figure 1), which accounts for a molecular mass of 478.70g/Mol. It is used to reduce cardiovascular problems, act as amebicide and was found to inhibit Mycobacterium tuberculosis under in-vitro assay condition4.

Phenolic acids
The leaf contains phenolic acids such as protocatechuic acid (Figure 2), coumaric acids, caffeic acid (Figur3), chlorogenic acid, and coumarin (Figure 4)5,2. These are known as esterified phenolic compounds6.  These compounds are linked with malic acid by an ester linkage.

Fig. 2. Structure of protocatechuic acid5

Protocatechuic acid
It is 3,4-dihydroxybenzoic acid(C7H6O4) (Figure 2). It is a type of antioxidant polyphenol.

p, m, o-Coumaricacids and caffeicacid
Coumaric acids are hydroxyl derivatives of cinnamic acid (Figure 3). p-Coumaric acids possess anti-oxidant property, which results in the inhibition of the low density lipoprotein oxidation7.
p-Coumaric acid (3) R1=R3=R4=H, R2=OH
m-Coumaric acid (1a) R1=OH, R2=R3=R4=H
o-Coumaric acid (1b) R1=R2=R3=H, R4=OH
Caffeic acid (5) R1=R4=H, R2=R3=OH

Fig. 3. Structure of coumaricandcaffeicacids5

Chlorogenic acid
It is a polyphenol compound, belongs to the family of esters of hydroxyl cinnamic acids, and has antioxidant effects. The molecular formula is C16H18O9 (Figure 4). Molecular mass is 354.31g mol–1. This can form an ester linkage with caffeic acid and quinic acid.

Fig. 4. Structure of chlorogenicacids5

Coumarin
Its molecular formula is C11H10O4 (Figure 5) and the molecular weight is 206.19gmol–1.

Fig. 5. Structure of 5, 7-dimethoxycoumarin5

Flavonoids
Flavonols (0–2,000 ppm) are the types of flavonoids. The leaf contains kaempferol and quercetin and other glycosylated flavonols such as manghaslin, clitorin, nicotiflorin, and rutin6.

Kaempferol and Quercetin
Kaempferol (C15H10O6) and quercetin (C15H10O7) (Figure 6) are main flavanols present in Carica papaya L. leaves.
Kaempferol (6) R1=R2=R3=R4=OH, R5=H
Quercetin (7) R1=R2=R3=R4=R5=OH

Fig. 6. Structure of kaempferol and Quercetin5

Other Phytochemicals
Tannins (5,000–6,000 ppm), phytosterol, cardiacglycosides, saponin glycosides, iridoids, anthraquinones, and organic acids such as malic acid, minor quantities of various malic acid derivatives and quinicacid are present in the leaves6.

Biochemicals
Vitamins
The extracts are very rich in the anti-oxidant vitamins such as vitamin A (7873.4 mg/kg), folic acid (2.4mg/kg), vitamin B12 (2.8 mg/kg), and vitamin C (89.0 mg/kg)8.

Minerals
The leaf contains Ca (8612.50 mg/Kg), Mg (67.75mg/Kg), Na (1782.00mg/Kg), K (2889.00 mg/Kg), Fe (90.50mg/Kg), Mn (9.50 mg/Kg)9 and calcium oxalate.  Other essential growth-promoting biochemicals are aminoacids such as proline and glutamine, enzymatic proteins such as a-amylase, b-amylase, and carbohydrate such as starch and cellulose.

Fatty acids
Linoleic (Figure 7) acid is an unsaturated omega-6 fatty acid. Linolenic acid (Figure 8) is an omega-3 fatty acid. These two compounds were found to show anti-malarial property in in-vitro biological assay conditions10.

Fig. 7. Structure of linoleic acid (9, 12-octadecadienoic acid)

Fig. 8. Structure of linolenic acid (9, 12, 15-octadecatrienoic acid)

Pharmacognostics properties of the leaves
Antibacterial activity
The in-vitro activity against clinical pathogens such as Klebsiella pneumonia, K.oxytocin, Enterococcus faecalis, Proteus mirabilis11, Escherichia coli, Pseudomonas aeruginosa12, Salmonella typhi13, Salmonella paratyphi A, Shigella flexneri14, Streptococcus pyogenes, Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus has been detected in the leaf extract using agar and disk diffusion methods.

Anti-fungal activity
Carica papaya leave extracts have broad spectrum anti-fungal activity against Aspergillus flavus, Candida albicans, Trichophyton rubrum,  T. mentagrophytes15,16, Cryptococcus neoformans, Candida tropicalis, and C. kefyr17. Colletotrichum gloeosporioides, Rhizopus stolonifer, and Fusarium spp.18 were also inhibited.  The dry leaves can control the radial growth of mycelia of Fusarium verticillioides19.  An aqueous extract controlled Alternaria sp., Fusarium sp., Pestalotiopsis sp., and Rhizopus sp.20

Anti-helminthic
The leaf extract at 5% concentration caused paralysis to the Pheretima posthuma, an Indian adult earthworm21.The healthy leaves were used to cure ascariasis infection caused by a pathogenic form of Ascaridia galli22and Ancylostoma caninum in an in-vivo mouse animal model23.

Antitumor activity
The leaf extracts can block the proliferative responses in cervical carcinoma, breast adenocarcinoma, hepatocellular carcinoma, lung adenocarcinoma, and pancreatic epithelial carcinoma. Apart from these, the leaf extracts also help in protecting the vascular systems and functional systems.  It mediated Th1 type shift in human and acted as a potent anti-tumor agent in an in-vitro assay24.

Immunostimulant activity during DENV viral infection
In a study, a leaf extract was orally administered to the patients to reduce the dengue viral symptoms. It increased the thrombocyte25 and platelet count in a mouse model infected with dengue virus.  During the dengue viral infection, a crushed leaf extract was found to improve the body immunity1.

Antioxidant effect
The leaf contains flavonoids (quercetin), phenols, tannins26 and vitamins as the source of natural anti-oxidants. It has a potent hydroxy radical scavenging activity as found in some in-vitro conditions.  It reduced acrylamide induced oxidative stress in stomach, liver, and kidney in an in-vivo animal model27.  In an in-vitro assay, it scavenged1,1-diphenylehydrazyl (DPPH), 2,2- azinobis-(3-ethyle benzothiazoline-6-sulfonate) (ABTS), nitric oxide, superoxide, and lipid peroxide in rat brain and liver28.  It inhibited nitric oxide and TNF-a production in in-vitro conditions29.  It reduced alcohol-induced acute gastric damage and blood oxidative stress in Sprague-Dawley rats30.

Hepatoprotective effect
The fresh leaves of the plant are traditionally used to cure liver associated problems.The leaf extracts help regularize liver enzyme during cirrhosis, hepatitis, and jaundice conditions.  Carbon tetrachloride-induced liver damage was rectified by the aqueous extracts of C. papaya leave in in-vivo animal models31. The freeze-dried leaf extracts considerably protected hepatic cells from oxidative injury caused by tert-butyl hydroperoxide in in-vitro conditions.  This chemical induced free radicals were scavenged by the anti-oxidants, phenolic and flavonoids, which are present in the leaves32.

Anti-inflammatory effects
The leaves also act as analgesic.  It can reduce carrageenan induced paw oedema, cotton pellets induced granuloma, and formaldehyde induced arthritis in in-vivo models33.  It could reduce Salmonella typhi infection induced inflammation in albino rats34.

Hypoglycemic effect
The extracts showed a significant hypoglycemic effect in in-vivo rat animal models35, where diabetes was induced by streptozotocin36.

Anti-sickling effect
The methanolic extracts of the leaves protected the membranes and reduced the sick cell formation under in-vitro conditions37.

Anti-gout effect
Xanthine oxidase enzyme is primarily involved in gout.  The dry leaf extracts are the source of xanthine oxidase inhibitors, which can act as an anti-gout agent38.

Toxicity
The leaf extracts showed no pathological differentiation forms in the tissues and there were no contrary effects on the major functional organs like liver, kidney, and bone marrow by its aqueous extracts in in-vivo animal models.Thus the leaf extracts were found to be safe.

CONCLUSION

Carica papaya L. leaves contain chemicals that are multi-functional and of a great medicinal importance.  Several in-vitro and in-vivo studies have approved its therapeutic efficacy and attainable mechanisms against newly emerging infectious diseases.  However, further research is required for the development of potential anti-viral drugs from this leaf.  The immunity development mechanisms during dengue viral infections have confirmed the anti-viral efficacy of Carica papaya L. leaves.  The further exploration of dengue viral control mechanism is required and it may lead to the development of several anti-viral therapies.  The toxicity level of pawpaw leaves is less and it doesnot hinder the medicinal beneficial effect.  Therefore, the ethanomedicinal usage of these leaves is much safer than any other synthetic drugs.

Declarations

ACKNOWLEDGMENTS
Our special thanks to Prof. Naoki Yamamoto, ID lab, Department of Microbiology, Yong Loo Lin School of Medicine, the National University of Singapore for anti-DENV studies.

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