Keywords:Carica Papaya, Lleaf extract, Anti-dengue, Anti-cancer
Carica Papaya is a traditional plant of tropical regions. It is a popular fruit as the best vitamin-A supplement and in the treatment of various helminthic infections. All parts of the plant have been proved for various activities in vitro. The current review pinpoints the activities of leaf extract exclusivelyfor their inflammatory, anti-oxidant, anti-cancer, anti-dengue, anti-platelet and against few antiviral effects for the future studies to be performed against resistant infections and other diseases for the benefit of the society.
Carica papaya (C. papaya, family Caricarceae, papaya) is one of the most popular and economically important tropical plants in the world [1, 2]. The plant is lactiferous which makes it an abundant source of endopeptidases or proteolytic enzymes like papain, chymopapain, glycyl endopeptidase and carican[3]. The plant also is rich in bioactive secondary metabolites like alkaloids, phenolics, Carbohydrates, terpenoids, phytosterols, glycosides, flavonoids, carotenoids, tannins, saponins. Leaves contain an alkaloid called carpaine and a glucoside named carposide[4]. All these compounds are responsible for the strong defensive mechanism which fascinated the research scientists. Few phenolic compounds like quercetin, protocatechuic acid, p-coumaric acid, caffeic acid, chlorogenic acid, kaempferol, and 5, 7-dimethoxycoumarin were isolated by GCMS[5].
Some of the traditional claims of efficacy that have been investigated scientifically using animal models and their efficacy have been proven [6, 7]. Recent studies conducted on leaf extract proved to possess anti-sickling (inhibition of sickle cell formation under severe hypoxia conditions) and membrane stabilizing properties[6,8]. The in vitro studies conducted on rats showed increased erythrocyte glutathione peroxidase activity and reduction of plasma lipid peroxidation level thus serving as a good therapeutic agent for protection against gastric ulcer and oxidative stress [6, 7]. It was also reported that the leaf extract possess an ability to modulate inflammatory markers in various cell types exposed to a variety of stressors due to the presence of proteolytic enzymes[9,10]. Studies also showed that
The leaf extracts were tested for their natural antibacterial properties against Bacillus stearothermophilus, Listeria monocytogenes, Pseudomonas sp., and Escherichia coli etc[12]. Research showed that the leaf extract possesses angiotensin converting enzyme inhibitory effect and reduced cardiac hypertrophy thus acting as a natural antihypertensive agent [12]. Carica papaya leaf extracts are used as a powerful cardiotonic and also for the treatment of fever, pyrexia, diabetes, gonorrhea, syphilis, inflammation and for dressing foul wounds. Traditionally, the leaf extract was used as analgesia and in the treatment for dyspepsia, colic, pyrexia, beriberi, abortion, hypertension, asthma [13-16] and cancer in Australia.
Scientific research on aqueous leaf extract showed antitumor activity by the induction of apoptosis and growth inhibitory activity. In addition it was also reported to increase the production of Th1 type cytokines such as the interleukins 1L 12p40 and IL 12p70, interferon (IFN Y) and tumour necrosis factor (TNF α) and expression of 23 immuno-modulatory genes in peripheral blood mononuclear cells[11]. A study conducted using aqueous and ethanolic extracts of C. papaya leaves were found to be more effective in inhibiting the proliferation in pancreatic cells [11]. The effects of Carica papaya leaf extracts have previously been reported being tested on the growth of different cancer cell lines: breast, stomach, lung, pancreatic, colon, liver, ovarian, cervical, neuroblastoma, lymphoma, leukaemia and other blood cancers. And the leaf extracts were found to exert in vitro cytotoxicity on human squamous cell carcinoma[13, 14].
Three groups of bioactive compounds identified by Huang et al., 2009 have attracted considerable interest in anticancer studies: phenolics, carotenoids and glucosinolates that are available in carica papaya leaves. Pure compounds of these three groups have been extensively researched in
|
|
|
|
|
| Stomach cancer cell line (AGS)Pancreatic cancer cell line (Capan1)Colon cancer cell line (DLD-1)Ovarian cancer cell line (Dov-13)Lymphoma cell line (Karpas)Breast cancer cell line (MCF 7) Neuroblastoma cell line (T98G)Uterine cancer cell line (Hela)T cell leukaemia cell line (CD26 negative or negative Jurkat) | Aqueous extract of papaya leaves (1.25–27 mg/mL) | Papaya leaf extract showed a concentration-dependent anticancer effect on each of the cancer cell lines, and suppressed DNA synthesis by suppressing the incorporation of 3H-thymidine | Morimoto et al., 2008 |
| T cell lines (H9, Jurkat, Molt-4, CCRF-CEM and HPB-ALL) Burkitt’s lymphoma cell lines (Ramos and Raji) Chronic myelogenous leukaemia cell line (K562) Cervical carcinoma cell line (Hela) Hepatocellular carcinoma cell lines (HepG2 and Huh-7) Lung adenocarcinoma cell line (PC14) Pancreatic epithelioid carcinoma cell line (Panc-1) Mesothelioma cell lines (H2452, H226, and MESO-4) Plasma cell leukaemia cell line (ARH77) Anaplastic large cell lymphoma cell line (Karpas-299) Breast adenocarcinoma cell line (MCF-7) Mesothelioma cell line (JMN) Pancreatic adenocarcinoma cell line (Capan1) | Aqueous extract of papaya leaves (0.625–20 mg/mL) | Otsuki et al., 2010 | |
| Human pancreatic cancer cells (Mia-Paca2 and ASPC-1) | Saponin-enriched water and ethanolic extracts (100 μg/mL) | Ethanolic extracts were more effective than or at least as effective as the chemotherapeutic agent, gemcitabine. | (Vuong et al., 2015) |
| Breast cancer cell line (T47D) | Protein fraction containing ribosome-activating proteins isolated from leaves | The protein fraction possessed cytotoxicity: IC50 = 2.8 mg/mL). Induction of apoptosis by regulation of p53 and BCl-2 protein expression (increased by 59.4% and decreased by 63% | Rumiyati, 2006 |
The studies also showed that the leaf extract possesses a dengue-specific neutralizing effect on dengue viral-infected plasma that may exert a protective role on platelets [19, 20].The findings revealed quercetin has potential inhibitory activity against NS2B-NS3 serine protease with marked antiviral activity against DENV2 virus as an effective anti-dengue compound[19, 20]. The activities of leaf extracts of Carica Papaya are represented as shown in the table: 2[21-27].
|
|
|
|
|
|
| 1 | Ethanol | Oral-25–200 mg/kg | Significant ( |
(Bamidele V.Owoyele et al. 2008) |
| 2 | Aqueous | Oral-100–200 mg/kg | Leaf extract found to contain alkaloids, tannins, cardiac glycosides and saponins. Extract displayed significant ( |
Adeolu and Vivian 2013 |
| 3 | Juice | Oral - 0.2 ml, 7 d | Platelet count was enhanced after 21 d (5.53 × 105/μl to 11.3 × 105/μl) in mice. Increment in RBC count also observed (6 × 106/μl to 9 × 105/μl) | (Dharmarathna et al. 2013 |
| 4 | Ethanol (70%) | Oral - 1.1g, twice daily, 12 d | Significant ( |
Fenny et al. 2012 |
| 5 | Oral - 150 ml, daily, 5 d | Increment in thrombocytes (28 × 103/μl to 138 × 103/μl) and WBC (3000/μl to 7800/μl) in male dengue fever patient | (Osama et al. 2014, | |
| 6 | Oral - 25 ml, twice daily, 5 d | Increment in platelets (55 × 103/μl to 168 × 103/μl), RBC (5.0 × 106/μl to 5.3 × 103/μl), WBC (3.7 × 103/μl to 7.7 × 103/μl) and PMN (46.7% to 78.3%) in male dengue fever patient | Ahmad et al. 2011 | |
| 7 | Oral - 0.72 ml/100 g | Both mature and immature leaves displayed platelet enhancing property with no signs of toxicity and stress in rats | Achini et al. 2012 | |
|
|
|
|
|
|
| 8 | Juice | Oral - 50 g, daily, 3 d | Mean platelet count enhanced in dengue fever patients at 40 h of first dose. |
Soobitha et al. 2013 |
Dose and dosage regimen play a vital role in the therapeutic activity of the constituent. Also excess doses may cause toxic effects and on toward reactions. Considering the history of the usage of leaves for various effects, the leaf extract is formulated as syrups and tablets as stable and convenient oral dosage forms. Currently leaf extract in the form of syrup or tablets are successfully being used in the control of the progression of cancer and also in the improvement of platelet count which is the major cause in the adverse effects of dengue.
The leaves of Carica Papaya, a traditional tropical plant has been studied extensively for its chemical constituents like endopeptidases, alkaloids, phenolics, Carbohydrates, terpenoids, phytosterols, glycosides, flavonoids, carotenoids, tannins, saponins. The presence of all these compounds revealed various potential therapeutic effects like immune-modulatory and anti-inflammatory effects, anticancer, anti-dengue etc apart from its traditional uses like antihypertensive, wound healing, malaria, fungal infections, asthma, diabetes, ulcers, eczema, helminth infections etc. Further studies are still encouraged to prove the possible therapeutic efficacy of leaf extracts of Carica Papaya against various antiviral agents and other diseases as natural treatment against dreadful diseases.
Ong H, Chua S, Milow P, Ethno-medicinal plants used by the Temuan villagers in Kampung Jeram Kedah, Negeri Sembilan, Malaysia. Ethno Med.5, 2011, 95–100.
Jiao Z, Deng J, Li G, Zhang Z, Cai Z, Study on the compositional differences between transgenic and non-transgenic papaya (
Thomás GE, Rodolfo HG, Juan MD, Georgina SF, Luis CG, Ingrid RB, et al, Proteolytic activity in enzymatic extracts from
Rivera-Pastrana DM, Yahia EM, González-Aquilar GA, Phenolic and carotenoid profiles of papaya fruit (
Canini A, Alesiani D, D’Arcangelo G, Tagliatesta P, Gas Chromatography-Mass Spectrometry analysis of phenolic compounds from Carica Papaya L. Leaf, J Food Compos Anal. 20, 2007, 584-589.
Indran M, Mahmood AA, Kuppusamy UR. Protective effect of
Imaga NO, Gbenle GO, Okochi VI, Akanbi SO, Edeoghon SO, Oigbochie V, et al, Antisickling property of
Naiho AO, Okankwor BC and Okoukwu C, Anti-Sickiling and membrane stabilizing Effects of Carica Papaya Leaf Extract. British. J. Medicine and Medical Res, 6(5), 2015, 484-492
Chanput W, Mes JJ, Wichers HJ. 2014. THP-1 cell line: An
Thao TT, Nguyen, Paul N Shaw, Marie-Odile Parat and Amitha K. Hewavitharana. Anticancer activity of Carica Papaya: A review. Mol.Nutr. Food Res, 57, 2013, 153-64.
Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C. 2010. Aqueous extract of
Girlandia Alexander Brasil, Silas N. Ronch et., al Antihypertensive Effect of Carica Papaya Via a Reduction in ACE Activity and Improved Baroreflex. Planta Med, 80, 2014, 1580- 1587 (Abstract)
Huang, WY, CAI, YZ and Zhang Y, Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutrition and cancer
Thao T. Nguyen, Marie-Odile Parat, Mark P. Hodson, Jenny Pan Paul N. Shaw, and AmithK. Hewavitharana Chemical Characterization and
Morimoto C and Dang NH, Compositions for cancer prevention, treatment, or amelioration comprising papaya extract, 20080069907. US Patent.
Vuong QV, Hirun S, Chuen, TL, Goldsmith CD, Murchie S, Bowyer MC, Phillips PA and Scarlett CJ, Antioxidant and anticancer capacity of saponin‐enriched Carica papaya leaf extracts. Int. J. Food Sci. & Techn. 50, 2015
Rumiyati SA, Effect of the protein fraction of Carica papaya L. leaves on the expressions of p53 and Bcl-2 in breast cancer cells line. Majalah farmasi Indonesia: Indonesian journal of pharmacy
Sinhalagoda L, Chandi Asoka Dharmarathna, Susiji Wickramasinghe,, Roshitha Nilmini Waduge, Rajapakse Peramune Veddikkarage Jayanthe Rajapakse, and Senanayake Abeysinghe Mudiyanselage Kularatne,Does
Chinnappan S, Ramachandrappa VS, Tamilarasu K, Krishnan UM, Pillai AK, Rajendiran S. Inhibition of Platelet Aggregation by the Leaf Extract of Carica papaya During Dengue Infection: An In Vitro Study
Bamidele V.Owoyele, Olubori M. Adebukola et.al., Anti-inflammatory activities of ethanolic extract of
Adeolu AA, Vivian EO. 2013. Anti-nociceptive and antiinflammatory studies of the aqueous leaf extract of Carica papaya in laboratory animals. Asian J Exp Biol Sci. 4:89–96.
Dharmarathna SL, Wickramasinghe S, Waduge RN, Rajapakse RP, Kularatne SA, Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model. Asian Pacific J Trop Biomed. 3, 2013, 720–724.
Fenny Y, Endang H, Jusuf KJ, The effect of Carica papaya L. leaves extract capsules on platelets count and hematocrit level in dengue fever patient. Int J Med Aromatic Plants 2, 2012, 573–578
Osama S, Ayesha S, Mohammad FI, Effects of papaya leaves on thrombocyte counts in dengue: A case report. J Pakist Med Assoc. 64, 2014, 364–366.
Ahmad N, Fazal H, Ayaz M, Abbasi BH, and Mohammad I, Fazal L, Dengue fever treatment with Carica papaya leaves extracts. Asian Pacific J Trop Biomed. 1, 2011, 330–333.
Achini G, Ratnasooriya WD, Jayakody JR, Charmain F, Chamini K, Preethi VU. Thrombocytosis and antiinflammatory properties, and toxicological evaluation of Carica papaya mature leaf concentrate in a murine model. Online Int J Med Plants Res. 1, 2012, 21– 30.