A Review on Pharmacognosy and Pharmacological Activity of Carica papaya Leaf

 

Mohini Shelke, Avesh Tamboli, Pankaj Sonawane, Priyanka Sadaphal, S.D. Mankar

Pravara Rural College of Pharmacy, Pravaranagar A/p Loni 413736 Tal – Rahata, Dist – Ahmednagar.

*Corresponding Author E-mail: sdmankar655@gmail.com

 

ABSTRACT:

Carica papaya has been used for centuries in many non-Western medical practices (e.g., Ayurveda, Traditional Chinese and Vietnamese, Unani) for its homeostatic and health-promoting properties. Anecdotal reports have recently surfaced indicating the daily consumption of tea extract made from C. papaya has been related to cancer remission, including remission from certain advanced solid tumor cancers. As a result, we set out to investigate C. papaya leaf extract's in vitro effects on human cancer cells as well as its in vivo effects in cancer patients using scientific methodologies.The phytochemical composition of C. papaya leaf extract was determined using liquid chromatography-mass spectroscopy (LC-MS), immune-modulatory and anti-cancer properties were analyzed in peripheral blood mononuclear cells and various solid tumor cell lines, and clinical laboratory measurements were examined in 116 cancer patients who obtained capsules of C. papaya leaf extract.Our findings suggest that C. papaya has a lot of promise as an adjuvant therapy for certain cancers, and further research is required. In cultured cancer cells, papaya extract tends to be toxic, meaning that it may be used as a drug. For the first time, scientists discovered that papaya leaf extract increases the development of Th1-type cytokines, which are important signaling molecules. In addition to papaya's direct anti-tumor effect on a variety of cancers, this immune system control indicates potential cancer-fighting therapeutic strategies. Th1-type cytokines are important signaling molecules that are increased by papaya leaf extract. Researchers subjected 10 different types of cancer cell cultures to four strengths of papaya leaf extract and assessed the effect after 24 hours, preventing a typical and destructive outcome of many cancer therapy regimens. In every society, papaya inhibited tumor growth.

 

KEYWORDS: Carica papaya, Anticancer, Anti-inflammatory, Immunomodulatory, Phytochemical, papaya leaves, antioxidants, polyphenols, Th1-type cytokines, Papaya leaf extract (PLE).

 

 


INTRODUCTION:

The papaya is common to several tropical regions of the planet. Papaya leaves and their extracts are sold as dietary supplements to enhance the system and increase platelet counts. papaya is usually found in tropical areas round the world. The fruits are consumed as food and medicine. Dried and powdered stems and leaves are prepared as medicinal teas to guard against infections and improve digestion. Papaya leaves and their extracts also are marketed as dietary supplements to reinforce the system and improve platelet function. The leaf extracts contain antibacterial compounds that inhibit bacterial growth. Hypoglycemic effects were reported with its use during a diabetic rat model and therefore the extract also appears to possess low toxicity. juice and pure lycopene, a component present in papaya, caused necrobiosis within the cancer of the liver cell line, Hep G2, with the half maximal inhibitory concentration (IC 50) of 20 µg/mL and 22.8 µg/mL, respectively. Papaya seed extract also exhibited anticancer activity in acute promyelotic leukemia HL-60 cells at IC 50 of 20 µg/mL whereas papaya pulp extract didn't have any effect even at a degree of 100 µg/mL. papaya are often effective against prostatic adenocarcinoma due to its lycopene content.

 

Fig No. 01: Carica papaya Leaf

                                                        

Fig No. 02: Carica papaya Fruit

 

The papaya belongs to a little family — Caricaceae. The fruits, leaves and latex obtained from papaya plant are used medicinally and for various other purposes. Papain, a chemical compound derived from fruit, stem latex, is used in the brewing and winemaking industries, as well as the textile and tanning industries1-3.Papaya contains broad spectrum of phytochemicals including, polysaccharides, vitamins, minerals, enzymes, proteins, alkaloids, glycosides, fats and oils, lectins, saponins, flavonoids, sterols, etc. Papaya, a juicy and attractive fruit, belonging to Caricaceae is scientifically known as papaya Linn. it's grown in various parts of the earth, including India, tropical America and Europe. It is commonly mentioned as Papaya, Pawpaw or papau, Kapaya, Lapaya, Papyas, Papye, Tapayas, Fan mu gua. Papaya plant is laticeferous as they contain specialized cells mentioned as laticifers. Lactifiers secrete latex and dispersed throughout most plant tissues papaya is actually short-lived Indian tree. within the historic times, it was considered as an exotic fruit thanks to its buttery taste and appearance. Papaya was the first genetically modified fruit consumed by citizenry for its nutritional and medicinal properties. Plant derived drugs widely used to treat cancer. However, their dose associated side effects, and toxicity to non-tumor tissues negatively affect their utility.As a result, alternative cancer treatments that have little to no impact on healthy tissues are highly desirable.A currently useful strategy used to evaluate herbal extracts is to see in vitro (Hoelder et al., 2012) for his or her selective anti-proliferative activities against cancer cells as compared to normal cells.The papaya plant could also be a nutritionally abundant source of vitamins A, B and C and also an honest source of calcium and iron. It contains the enzyme papain, which aids digestion and is used to treat ulcers and a number of microbial diseases, with higher doses being especially effective against gram-negative bacteria. The photochemical investigation suggested that young leaves contain alkaloids, saponin, tannin, flavonoid and glycosides, hence have therapeutic properties like antibacterial, anti-inflammatory, antiviral, hypoglycaemic antitumor and many others.

 

Pharmacognosy:

Kingdom:              Plantae

Order:                    Brassicales

Family:                  Caricaceae

Genus:                   Carica

Species:                 C. papaya

 

Pharmacognostical Study:

The papaya tree is typically a thin, single-stemmed plant with sparse branching. It reaches a height of 15 to 30 feet and has spirally arranged leaves that are restricted to the highest branches. Leaves and fruits scars can be seen on the lower trunk. The leaves are palmately lobed with seven lobes and are wide, measuring 50-70cm (20-28 in) in diameter. Trees are dioecious, and latex is found in all areas of the tree. The flowers have five sections and the stamens fuse to the petals of male flowers, making them extremely dimorphic. In female flowers, there is always a superior ovary and five contorted petals. Within the leaf axils, both male and female flowers remain.  In the dusk, the sweet-scented flowers remain open. It produces a large berry-like fruit with a diameter of 10 to 30 cm and a length of 15 to 40 cm. The Caricaceae family includes C. papaya, also known as pawpaw. The papaya is a large, tree-like plant with a single stem that grows to a height of 5 to 10 meters (16 to 33 feet) and spirally arranged leaves restricted to the highest part of the trunk. The lower trunk is scarred where leaves and fruits were produced. over pith was discovered to be missing. The leaves are wide, with seven lobes and a length of 50–70 cm. The leaves of Carica papaya Linn. were studied and recorded in order to establish quality standards. Epidermis, collenchymas and parenchyma, sclerenchyma, xylem, phloem, and pith were found to be present in the microscopic examination.

 

Phytochemicals:

The structures of bioactive secondary metabolites are:

 

Fig No. 03: Chemical Structures of compounds present

 

Therapeutic Applications of Carica papaya:

Anticancer Activity:

Papaya is employed for preventing and treating alimentary canal disorders, intestinal parasite infections, and as a sedative and diuretic. it's also used for nerve pains (neuralgia) and elephantoid growths. Elephantoid growths are large swollen areas of the body that are symptoms of a rare disorder of the systema lymphaticum caused by parasitic worms. Papaya contains a chemical called papain, which is usually used as a meat tenderizer. Consumption of papaya has been related to a lower risk of gallbladder and colorectal cancers, according to research. Diabetes is a disease that affects millions of people According to preliminary studies, eating fermented papaya daily for two months will lower blood glucose levels in diabetics. Human papillomavirus (HPV) infection. Consumption of papaya has been linked to a lower risk of HPV infection, according to research. Otsuki et al. demonstrated that papaya has been utilized for its indigenous activity and purported for the ostensible anticancer properties it acquires a standing as a tumor-destroying agent. The presence of saponins supports the very fact that papaya leaf has cytotoxic effects,96 while vitamin C leads the plant to be utilized in herbal medicine for treatment of prostatic adenocarcinoma. Moreover, its juice has been shown to possess an antiproliferative effect on cancer of the liver cells. consistent with an anticipated biosynthetic trail, lycopene is that the central and key compound (the most abundant carotenoids), which indicates high stimulation of its upstream steps during the stage of ripening. Likewise, Armando illustrated the protective action of papaya against atrophic arthritis, renal failure, and prostatic adenocarcinoma. It exhibits a potent antioxidant action that has the power to neutralize free radicals, thereby conferring defense against different sorts of cancer like carcinoma, prostatic adenocarcinoma, atherosclerosis, and associated arteria coronaria disease also.

 

Mechanism of action

The system is modulated by papaya leaf extract, which increases the production of Th1 cytokines such as interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF-gamma) (TNF-alpha). Cancer cell growth is hindered most efficiently by fractions with a relative molecular mass of less than 1000. Antioxidant properties and antibacterial and phenolic compounds are found in papaya leaf extract, but the mechanism of action is unknown. With half maximal inhibitory concentrations (IC 50) of 20 g/mL and 22.8 g/mL, respectively, papaya juice and pure lycopene, a component found in papaya, induced necrobiosis in Hep G2 cancer cells. In acute promyelotic leukemia HL-60 cells, papaya seed extract had anticancer activity at a concentration of 20 g/mL, while papaya pulp extract had no effect even at a concentration of 20 g/mL.Interestingly no human clinical trials were performed as yet; however, survival was observed in patients with carcinoma, stomach cancer, carcinoma, carcinoma, cancer of the liver, after drinking papaya leaf extract. Papaya are often effective against prostatic adenocarcinoma due to its lycopene content.

 

Antipyretic/Dengue fever/Platelets enhancer Activity

Papaya leaves contain natural plant compounds such as flavonoids and carotenes, which are strong anti-inflammatory and antioxidant molecules that prevent harmful free radicals from damaging cells in the body. Furthermore, papaya leaves contain a special phytochemical called acetogenin, which has anti-malarial properties, increasing platelet count and aiding in the fast recovery of dengue patients. Lab studies suggest that papaya leaf extracts may inhibit a spread of bacteria and improve platelet counts. Although a study in humans also suggests it can improve platelet counts in patients with dengue, a meta-analysis found that evidence was lacking. More study is required on dosing, safety, and effectiveness before papaya leaf extract are often used for this purpose.

 

Mechanism of Action:

Papaya leaf extract, made from dried or fresh ground leaves, contains a wide range of compounds, including flavonoids and other plant phenols, as well as alkaloids such as carpaine, anthraquinone, saponins, cardiac glycosides such as carposide, and tannins. Thus, it's rich in antioxidant and radical scavenging activity, also as having the ability to stabilize the RBC membrane.  The virus seeks out monocytes and macrophages, as well as endothelial cells, to feed on. As a result, focal apoptosis and even necrosis could also be observed, resulting in their infection, platelet aggregation, and peripheral destruction of platelets. Vascular permeability increases, due to the proinflammatory factors, as complement activation is additionally a result of the inflammatory cascade. According to one study, papaya leaf extract can neutralize dengue virus-infected plasma and significantly minimize platelet aggregation. The extract of papaya leaves has been shown to extend ALOX12 (arachidonate 12-lipoxygenase or platelet type lipoxygenase) by 15 times. By the the number and differentiationof megakaryocytes, this enzyme promotes platelet formation. The platelet-activating factor receptor (PTAFR) gene is unique to platelets and is increased 13.5-fold after the extract is given compared to controls. Dengue virus replication requires the serine proteases NS2B and NS3, but quercetin, one of the flavonoids present in papaya leaves, inhibits them. This extract thus prevents viral assembly. In one report, oral administration of papaya leaf extract was linked to a rapid increase in platelet count in as little as 24 hours. Within the overall WBC count, there was a significant increase.

 

Fig. 04: Therapeutic Benefits of Carica papaya

 

CONCLUSION:

The enzyme ALOX12 (arachidonate 12-lipoxygenase or platelet type lipoxygenase) was found to be 15 times more active when papaya leaf extract was used. By the number and differentiation of megakaryocytes, this enzyme promotes platelet formation. When compared to controls, fresh C. papaya leaf extract substantially increased platelet and RBC counts in the test sample. Therefore, it is vital to identify those chemicals of C. papaya leaves because it are often recommended to be used as a drugs to boost thrombopoiesis and erythropoiesis in humans and in animals during which these cell lineages are compromised. It are often concluded that papaya has potential anti-cancer compared to other medicinal plants. The phyotochemical properties were identified by the anti-cancerous activity through MTT assay, DNA fragmentation assay, caspase 7/9 induction detection assay and Annexin-V FITC assay and thru wound healing assay it's understood that it also has significant anti-metastatic activity.

 

REFERENCE:

1.        Abidina NZ, Omara H, Empungana AJ, Kamalaldinb NA, Yahayab BH and Zubairia SI: Proliferative Activity of Saponin-Reducing Carica papaya L. Leaves Extracts on Human Lung Fibroblast Cell (IMR90). Journal Teknologi November 2016.

2.        Agung N, Hesty H, Jae SC and, Hee-Juhn P: Identification and quantification of flavonoids in Carica

3.        Ahmad N, Fazal H, Ayaz M, et al. Dengue fever treatment with Carica papaya leaves extracts. Asian Pacific Journal of Tropical Biomedicine. 2011:330-333.

4.        Ahmad N: Dengue fever treatment with Carica papaya leaves extracts; Asian Pacific Journal of Tropical Biomedicine 2011; 4: 330-333.

5.        Bamisaye FA, Ajani EO, Minari JB. Prospects of ethnobotanicaluses of pawpaw (Carica papaya). J Med Plants. 2013;1(4):171–7.

6.        Baskaran C, Rathabai V, Velu S and Kubendiran K: The efficacy of Carica papaya L. leaf extract on some bacterial and a fungal strain by well diffusion method; Asian Pacific Journal of Tropical Disease 2012; 2(2): s658-s662.

7.        Bouayed J, Hoffmann L, Bohn T. Total phenolics, flavonoids, anthocyanins and antioxidant activity following simulated gastrointestinal digestion and dialysis of apple varieties: bioaccessibilityand potential uptake. Food Chem. 2011;128(1):14–21.

8.        Chavez Quintal P, Gonzalea-Flores T, Rodriguez-Buenfil and Gallegos-Tintore S: Antifungal activity in Ethanolic Extracts of Carica papaya L cv Maradol leaves and seeds; Indian Journal of Microbiology 2011; 51(1): 54-60.

9.        Chung-Shih T: New macrolcyclic, Δ1-piperideine alkaloids from papaya leaves: dehydrocarpaine I and II; Phytochemistry 1979; 18(4): 651-652.

10.      Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1-2):72–9.

11.      Dharmarathna SLCA, Wickramasinghe S, Waduge RN, Rajapakse RPVJ and Kularatne SAM: Does Carica papaya L. leaf extract increase the platelet count? An experimental study in a murine model; Asian Pacific Journal of Tropical Biomedicine 2013; 3(9):720-724.

12.      E, et al. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J Ethnopharmacol. Feb 17 2010;127(3):760-767.

13.      Focho DA, Newu MC, Anjah MG, Nwana FA and Ambo FB: Ethnobotanical survey of trees in Fundong, Northwest Region, Cameroon. J Ethnobiol Ethnomed. 2009; 5: 17.

14.      George M, Venkataraman PR and Pandalai KM: Investigation on plant antibiotics part II; A search for antibiotics substances in some Indian medicinal plants. Journal of Science and Industrial Research. 1947; 6B: 42-46

15.      Govindachari TR, Pai BR and Narasimhan NS: Pseudocarpine, a new alkaloid from Carica papaya L. J.Chem. Soc., 1954; 0: 1847-1849.

16.      Hu T, Guo YY, Zhou QF, Zhong XK, Zhu L, Piao JH, et al. Optimization of ultrasonic-assisted extraction of total saponins from Eclipta prostrasta L. using response surface methodology. J Food Sci. 2012;77(9):C975–82.

17.      Indran M, Mahmood AA, Kuppusamy. 5UR. Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats. West Indian Med J. Sep

18.      Juarez-Rojop IE: Phytochemical screening and hypoglycaemic activity of Carica papaya L. leaf in streptozotocin- induced diabetic rats. Revista Brasileira de Farmacognosia. 2014; 24(3): 341-347.

19.      Krishna KL, Paridhavi M, Patel JA. Review on nutritional, medicinal and pharmacological properties of papaya (Carica papayaLinn.). Nat Prod Radiance. 2008;7(4):364–73.

20.      Leader B, Baca QJ, Golan DE. Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov. 2008;7(1)21–39.

21.      Longdet IY, Adoga EA. Effect of methanolic leaf extract of Caricapapaya on plasmodium berghei infection in albino mice. Eur J MedPlants. 2017;20(1):1–7.

22.      Nguyen TT, Parat MO, Shaw PN, Hewavitharana AK, Hodson MP. Traditional aboriginal preparation alters the chemical profile ofCarica papaya leaves and impacts on cytotoxicity towards humansquamous cell carcinoma. PLoS One. 2016;11(2):1–15.

23.      Otsuki N, Dang NH and Morimoto EKASC: Aqueous extract of Carica papaya L. leaves exhibits anti tumor activity and immunomodulatory effects; Journal of Ethnopharmacology 2010; 127(3): 760-767.

24.      Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J Ethnopharmacol. 2010; 127(3): 760–7.

25.      Pandey S, Walpole C, Cabot PJ, Shaw PN, Batra J, Hewavitharana AK. Selective anti-proliferative activities of Carica papaya leafjuice extracts against prostate cancer. Biomed Pharmacother. 2017; 89:515–23.

26.      Pandey S, Walpole C, Cabot PJ, Shaw PN, Jyotsna B and Hewavitharana AK: Cancer; Biomedicine and Pharmacotherapy 2017; 89: 515-523.

27.      papaya L. leaf and peroxynitrite-scavenging activity; Asian Pacific Journal of Tropical Biomedicine 2017; 7(3):208-213.

28.      Patil T, Patil S, Patil A, Patil S. Carica papaya leaf extracts–anEthnomedicinal boon. Int J Pharmacog Phytochem Res. 2014; 6(2): 260–5.

29.      Paul BI, Nasreen MA, Sarker AN, Islam MR. Isolation, purificationand modification of papain enzyme to ascertain industrially valuable nature. Int J Biotechnol Res. 2013;3(5):11–22.

30.      Rahman S, Imran M, Muhammad N, et al. Antibacetial screening of leaves and stem of Carica papaya. Journal of Medicinal Plants Research. 2011; 5(20):5167-5171.

31.      Rahmani AH, Aldebasi YH. Potential role of Carica papaya andtheir active constituents in the prevention and treatment of diseases. Int J Pharm Pharm Sci. 2016;8(1):11–5.

32.      Ram PN, Ram VR, Khatri TT, Vyas SJ and Dave PN: XRF analysis of Carica papaya L. leaves of semi arid region of Kachchh. International Letters of Natural Sciences. 2014; 19: 15-24.

33.      Ramasawamy AM and Sirsi M: Antituberculosis Activity of Some Chemical Constituents from Higher Plants. Indian J. Pharm 1960; 22: 34-35.

34.      Sagnia B, Fedeli D, Casetti R, Montesano C, Falcioni G and Colizzi V: Antioxidant and Anti-Inflammatory Activities of Extracts from Cassia alata, Eleusine indica, Eremomastax speciosa, Carica papaya L. and Polyscias fulva medicinal plants collected in Cameroon; Plos one2014; 9(10).

35.      Sarala N, Paknikar SS. Papaya extract to treat dengue: a noveltherapeutic option?. Ann Med Health Sci Res. 2014;4(3):320–4.

36.      Saran PL, Choudhary R. Drug bioavailability and traditional medi-caments of commercially available papaya: a review. Afr J AgricRes. 2013;8(25):3216–23.

37.      Sathasivam K, Ramanathan S, Mansor SM, et al. Thrombocyte counts in mice after the administrationof papaya leaf suspension. Wiener klinische Wochenschrift. Oct 2009;121 Suppl 3:19-22.

38.      Seigler DS, Pauli GF, Nahrstedt A, Leen R. Cyanogenicallosides and glucosides from Passifloraedulis and Carica papaya. Phytochemistry. 2002;60(8):873–82

39.      SP Singh, SV Mathan, A Dheeraj, D Tailor, RP Singh, A Acharya.Anticancer effects and associated molecular changes of Caricapapaya against prostate cancer. AACR; Cancer Res. 2019;79(13): Abstract nr 3004.

40.      Suwendar PH and Ernasari GI: Analgetic activity of Papaya (Carica papaya L.) leaves extract; Procedia Chemistry 2014; 13: 147-149.

41.      Tang CS. Benzyl isothiocyanate of papaya fruit. Phytochemistry 1971;10(1):117–21.

42.      Tasqiah: HPLC- based activity profiling for antiplasmodial compounds in the traditional Indonesian medicinal plant Carica papaya L. Journal of Ethnopharmacology. 2014;155(1): 426-434.

43.      Thomas E, Vandebroek I, Sanca S and Van Damme P: Cultural significance of medicinal plant families and species among Quechua farmers in Apillapampa, Bolivia. J Ethnopharmacol 2009; 122: 60–67

44.      Vij T, Prashar Y. A review on medicinal properties of Carica papaya Linn. Asian Pac J Trop Dis. 2015;5(1):1–6.

45.      Vishwanath Z, Prasad DR, Mehul J, Trivedi B andNivsarkar M: Antithrombocytopenic activity of carpaine and alkaloidal extract of Carica papaya Linn. leaves in busulfan induced thrombocytopenic Wistar rats; Journal of Ethanopharmacology 2016; 181(2): 20-25.

46.      Wall MM. Ascorbic acid, vitamin a, and mineral composition ofbanana (Musa sp.) and papaya (Carica papaya) cultivars grown in Hawaii. J Food Compos Anal. 2006;19(5):434–45.

 

 

Received on 03.02.2020         Modified on 12.02.2020

Accepted on 18.02.2020  ©A&V Publications All right reserved

Res. J. Pharmacognosy and Phytochem. 2021; 13(4):200-204

DOI: 10.52711/0975-4385.2021.00035