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Drug Res (Stuttg)
DOI: 10.1055/a-2509-8644
Review

A Review of Potentials of Carica Papaya Leaves in Dengue Viral Infection – Insights of Clinical and Preclinical Studies

Naina Mohamed Pakkir Maideen
1   Dubai Academic Health Corporation, Dubai, UAE
,
Rajkapoor Balasubramanian
2   Department of Pharmacology, J.K.K. Nattraja College of Pharmacy, Komarapalayam, Tamilnadu, India
,
Arun Shanmugam
3   Department of Pharmacy Practice, J.K.K. Nattraja College of Pharmacy, Komarapalayam, Tamilnadu, India
,
Mirunalini Gobinath
4   JSS College of Pharmacy, Ooty, Tamilnadu, India
,
Mohamed Harshath Jahir Hussain
5   Ratnam Institute of Pharmacy, Nellore, Andhra Pradesh, India
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Abstract

Objective

One of the most widespread arboviral diseases in the world, dengue virus disease (DVD) is primarily found in tropical and subtropical regions, affecting 129 countries. The main way that the dengue virus (DENV) spreads is through the bite of a female Aedes aegypti mosquito. Symptomatic therapy and supportive care are the primary methods of managing patients with DENV infection as there is currently no approved antiviral medication for this condition. Since the guidelines from the AYUSH Ministry, Government of India, recommend 10 ml of carica papaya leaf extract (CPLE) twice daily for seven days, to treat dengue fever clinically, we plan to review the potential of carica papaya in managing DENV infection.

Methods

Using terms like dengue, dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and carica papaya, the literature was searched in databases like Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, Web of Science, EMBASE, Directory of open access journals (DOAJ), and reference lists to find articles relevant to the clinical, in-vivo, in-vitro, and in-silico studies evaluating the efficacy of carica papaya in the management of dengue viral infection. This review included English-language publications that supported the use of carica papaya in the treatment of dengue fever, but it excluded publications that were duplicates.

Results

Numerous preclinical and clinical investigations, such as in-vitro, in-vivo, and in-silico studies, have identified carica papaya's anti-dengue potential. The pleiotropic effects of carica papaya, including its anti-thrombocytopenic activity, immunomodulatory effects, and larvicidal property against the Aedes aegypti mosquito species, have also been confirmed by numerous in-vitro and in-vivo studies. These effects can help patients with dengue fever by elevating their platelet count and alleviating other symptoms.

Conclusion

To hasten recovery and reduce hospital stays, patients with DENV infection may take carica papaya leaf extract (CPLE) in addition to supportive care and symptomatic treatment. Additional randomized controlled clinical trials would be necessary to confirm the safety and effectiveness of CPLE in patients with DENV infection.

Keywords

antiviral drugs - drug research - infectious diseases


Publication History

Received: 09 July 2024

Accepted: 29 December 2024

Article published online:
22 January 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 5070469 Stuttgart, Germany

 

  • References

  • 1 Sabir MJ, Al-Saud NB, Hassan SM. Dengue and human health: A global scenario of its occurrence, diagnosis, and therapeutics. Saudi J Biol Sci 2021; 28: 5074-80.
    CrossrefPubMedSearch in Google Scholar
  • 2 Murugesan A, Manoharan M. Dengue virus. Emerging and reemerging viral pathogens. 2019. 281-359
    Crossref
  • 3 World Health Organization. Dengue and severe dengue. Available at https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue Published April 23, 2024. Accessed Sep 19, 2023.
    PubMed
  • 4 Guzman MG, Harris E. Dengue. Lancet 2015; 385: 453-465
    CrossrefPubMedSearch in Google Scholar
  • 5 Zhang H, Zhou YP, Peng HJ. et al. Predictive symptoms and signs of severe dengue disease for patients with dengue fever: a meta-analysis. Biomed Res Int 2014; 2014: 359308
    PubMedSearch in Google Scholar
  • 6 Sangkaew S, Ming D, Boonyasiri A. et al. Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis. Lancet Infect Dis 2021; 21: 1014-26.
    CrossrefPubMedSearch in Google Scholar
  • 7 Rathore AP, Farouk FS, John AL. Risk factors and biomarkers of severe dengue. Curr Opin Virol 2020; 43: 1-8
    CrossrefPubMedSearch in Google Scholar
  • 8 Sangkaew S, Ming D, Boonyasiri A. et al. Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis. Lancet Infect Dis 2021; 21: 1014-1026
    CrossrefPubMedSearch in Google Scholar
  • 9 Rather IA, Parray HA, Lone JB. et al. Prevention and control strategies to counter dengue virus infection. Front Cell Infect Microbiol 2017; 7: 336
    CrossrefPubMedSearch in Google Scholar
  • 10 Torres-Flores JM, Reyes-Sandoval A, Salazar MI. Dengue vaccines: an update. BioDrugs 2022; 36: 325-336
    CrossrefPubMedSearch in Google Scholar
  • 11 Tully D, Griffiths CL. Dengvaxia: The world’s first vaccine for prevention of secondary dengue. Therapeutic Advances in Vaccines and Immunotherapy 2021; 9 25151355211015839
    PubMedSearch in Google Scholar
  • 12 Halstead SB. Three dengue vaccines – what now. N Engl J Med 2024; 390: 464-465
    CrossrefPubMedSearch in Google Scholar
  • 13 Angelin M, Sjölin J, Kahn F. et al. Qdenga®-A promising dengue fever vaccine; can it be recommended to non-immune travelers?. Travel Medicine and Infectious Disease 2023; 54: 102598
    CrossrefPubMedSearch in Google Scholar
  • 14 Haque QM, Ahmed SM, Rahman MA. et al. Dengue Vaccine: Challenges and Limitations. KYAMC Journal 2023; 14: 172-174
    CrossrefPubMedSearch in Google Scholar
  • 15 Kamath V, Aishwarya AB. Dengue vaccines: Current status and future perspectives. APIK Journal of Internal Medicine. 2024: 10-4103
    PubMedSearch in Google Scholar
  • 16 Maideen NM, Hadda TB, Almalki FA. et al. Black seeds (Nigella sativa) for the management of Dengue viral disease: POM analyses for the identification of new antiviral pharmacophore sites. J Medicinal Herbs 2023; 14: 19-36.
    PubMedSearch in Google Scholar
  • 17 Guidelines for Siddha practitioners for clinical management of dengue fever. Central Council for Research in Siddha. Ministry of AYUSH, Government of India https://main.ayush.gov.in/research/guidelines-for-ayush-practitioners-for-clinical-management-of-dengue/ Accessed 24 Oct 2023
    PubMed
  • 18 Priyadarshi A, Ram B. A review on pharmacognosy, phytochemistry, and pharmacological activity of Carica papaya (Linn.) leaf. Int J Pharm Sci Res 2018; 9: 4071-4078
    PubMedSearch in Google Scholar
  • 19 Devi S, Ropiqa M, Murti YB. et al. Screening of Extraction Process and The Estimation of Total Alkaloids in Carica papaya Linn. Leaf. Majalah Obat Tradisional 2020; 25: 90-95
    CrossrefPubMedSearch in Google Scholar
  • 20 Nugroho A, Heryani H, Choi JS. et al. Identification and quantification of flavonoids in Carica papaya leaf and peroxynitrite-scavenging activity. Asian Pac J Trop Biomed 2017; 7: 208-13.
    CrossrefPubMedSearch in Google Scholar
  • 21 Ruhaizat-Ooi IH, Zainal-Abidin RA, Ab Ghani NS. et al. Understanding the complex functional interplay between glucosinolates and cyanogenic glycosides in Carica papaya . Agronomy 2022; 12: 2508
    CrossrefPubMedSearch in Google Scholar
  • 22 Vuong QV, Hirun S, Chuen TL. et al. Antioxidant and anticancer capacity of saponin-enriched Carica papaya leaf extracts. International Journal of Food Science & Technology 2015; 50: 169-177
    CrossrefPubMedSearch in Google Scholar
  • 23 Syed Amran SN, Zainal Abidin N, Hashim H. et al. Saponin bitterness reduction of Carica papaya leaf extracts through adsorption of weakly basic ion exchange resins. Journal of Food Quality 2018; 2018: 5602729
    CrossrefPubMedSearch in Google Scholar
  • 24 Ugo NJ, Ade AR, Joy AT. Nutrient composition of Carica papaya leaf extracts. J Food Sci Nutr Res 2019; 2: 274-282
    PubMedSearch in Google Scholar
  • 25 Santana LF, Inada AC, Espirito Santo BL. et al. Nutraceutical potential of Carica papaya in metabolic syndrome. Nutrients 2019; 11: 1608
    CrossrefPubMedSearch in Google Scholar
  • 26 Singh P, Singh RL, Pathak N. et al. Phytochemistry and nutraceutical properties of Carica papaya (Linn.): A review. Dietary Supplements and Nutraceuticals 2022; 1: 1-5
    CrossrefPubMedSearch in Google Scholar
  • 27 Hettige S. Salutary effects of Carica papaya leaf extract in dengue fever patients– a pilot study. Sri Lankan Fam Physician 2008; 29: 17-19
    PubMedSearch in Google Scholar
  • 28 Ahmad N, Fazal H, Ayaz M. et al. Dengue fever treatment with Carica papaya leaves extracts. Asian Pac J Trop Biomed 2011; 1: 330-333
    CrossrefPubMedSearch in Google Scholar
  • 29 Assir MZ, Mansoor H, Waseem T. et al. Effect of papaya leaf extract on platelet count in dengue fever: a randomized controlled trial (PLEAD Trial). Int J Infect Dis 2012; 16: e473
    CrossrefPubMedSearch in Google Scholar
  • 30 BSR Deepak Effect of papaya leaf juice on platelet and WBC count in dengue fever: a case report. J Ayurveda Hol Med (JAHM) 2013; 1: 26-29
    PubMedSearch in Google Scholar
  • 31 Subenthiran S, Choon TC, Cheong KC. et al. Carica papaya leaves juice significantly accelerates the rate of increase in platelet count among patients with dengue fever and dengue haemorrhagic fever. Evid Based Complement Alternat Med 2013; 2013: 616737
    CrossrefPubMedSearch in Google Scholar
  • 32 Siddique O, Sundus A, Ibrahim MF. Effects of papaya leaves on thrombocyte counts in dengue – a case report. JPMA J Pak Med Assoc 2014; 64: 364-366
    PubMedSearch in Google Scholar
  • 33 Kumar CV, Taranath V, Venkatamuni A. et al. Therapeutic Potential of Carica papaya L. Leaf Extract in Treatment of Dengue Patients. Int J Appl Biol Pharm Technol 2015; 6: 93-98
    PubMedSearch in Google Scholar
  • 34 Gowda AC, Kumar NV, Kasture PN. et al. A Pilot Study to Evaluate the Effectiveness of Carica papaya Leaf Extract in Increasing the Platelet Count in Cases of Dengue with Thrombocytopenia. Indian Med Gaz 2015; 149: 109-116
    PubMedSearch in Google Scholar
  • 35 Singhai A, Juneja V, Abbas S. et al. The effect of Carica papaya leaf extract capsules on platelets count and hematocrit levels in acute febrile illness with thrombocytopenia patient. Int J Med Res Health Sci 2016; 5: 9-12
    PubMedSearch in Google Scholar
  • 36 Kasture PN, Nagabhushan KH, Kumar A. A Multi-centric, Double-blind, Placebo-controlled, Randomized, Prospective Study to Evaluate the Efficacy and Safety of Carica papaya Leaf Extract, as Empirical Therapy for Thrombocytopenia associated with Dengue Fever. Journal Association of Physicians of India 2016; 64: 15-20
    PubMedSearch in Google Scholar
  • 37 Gadhwal AK, Ankit BS, Chahar C. et al. Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia. Journal Association of Physicians of India 2016; 64: 22-26
    PubMedSearch in Google Scholar
  • 38 Sundarmurthy D, Jayanthi CR, Lakshmaiah KC. Effect of Carica papaya leaf extract on platelet count in chemotherapy-induced thrombocytopenic patients: A preliminary study. Natl J Physiol, Pharm Pharmacol 2017; 7: 685
    CrossrefPubMedSearch in Google Scholar
  • 39 Hussain SM, Sohrab MH, Al-Mahmood AK. et al. Clinical use of Carica papaya leaf extract in chemotherapy-induced thrombocytopenia. Int J Clin Exp Med 2017; 10: 3752-3756
    PubMedSearch in Google Scholar
  • 40 Babu R, Kubavat S, Poulose KP. et al. A randomized, double-blind, placebo-controlled, proof of concept study to assess the safety and efficacy of Carica papaya and Tinospora cordifolia leaf extract (Thrombobliss) in subjects undergoing chemotherapy treatment and subjects with systemic microbial infection and subsequent reduction in platelet count. Int J Clin Trials 2017; 4: 116-121
    CrossrefPubMedSearch in Google Scholar
  • 41 Krishna AR, Myreddy N, Uppara S. Assessment of Platelet Levels in Serum Samples of Dengue Patients before and after Providing Papaya with Other Fruits. Ann Int Med Dent Res 2017; 3: 1
    PubMedSearch in Google Scholar
  • 42 Vijeth SB, Kauser MM, Mangsuli V. et al. Effect of Carica papaya leaf extract (CPLE) on thrombocytopenia among dengue patients of tertiary care hospital, Chitradurga, India. Int J Adv Med 2018; 5: 974-977
    PubMedSearch in Google Scholar
  • 43 Venugopal K, Suresh RM, Halesha BR. Role of Carica papaya leaf extract tablets/capsules on platelet counts in cases of dengue thrombocytopenia. Int J Adv Med 2018; 5: 845-848
    CrossrefPubMedSearch in Google Scholar
  • 44 Panda AK, Bhuyan G, Dattatray D. et al. Phyto extracts of Carica papaya and Tinospora cordifolia can correct thrombocytopenia in alcoholic decompensate liver cirrhosis: Case Series. J Ayurveda Integr Med Sci 2018; 3: 99-101
    CrossrefPubMedSearch in Google Scholar
  • 45 Vijeth SB, Kauser MM, Mangasuli V. et al. Effect of Carica papaya leaf extract (CPLE) on thrombocytopenia among dengue patients of tertiary care hospital, Chitradurga. India Int J Adv Med 2018; 5: 974-977
    CrossrefPubMedSearch in Google Scholar
  • 46 Tiwari R, Mandal DK, Patel J. A post-marketing randomized placebo-controlled study to evaluate the efficacy of study product UPLAT® (Carica papaya leaf extract+Tinospora cordifolia extract) in the cancer patients with thrombocytopenia induced by chemotherapy. Int J Clin Trials 2018; 5: 170-176
    CrossrefPubMedSearch in Google Scholar
  • 47 Srikanth BK, Reddy L, Biradar S. et al. An open-label, randomized prospective study to evaluate the efficacy and safety of Carica papaya leaf extract for thrombocytopenia associated with dengue fever in pediatric subjects. Pediatric health, medicine and therapeutics. 2019 10. 5-11
    PubMedSearch in Google Scholar
  • 48 Pandita A, Mishra N, Gupta G. et al. Use of papaya leaf extract in neonatal thrombocytopenia. Clinical Case Reports 2019; 7: 497-499
    CrossrefPubMedSearch in Google Scholar
  • 49 Shetty D, Manoj A, Jain D. et al. The effectiveness of Carica papaya leaf extract in children with European of biomedical and Pharmaceutical sciences the effectiveness of Carica papaya leaf extract in children with. Eur J Biomed Pharm 2019; 6: 380-383
    PubMedSearch in Google Scholar
  • 50 Spt LP, Jose JA. Safety and Efficacy Study of ZyboricaTM Tablet (Carica papaya Leaf Extract) for Thrombocytopenia Associated with Dengue Fever: A Randomized Double-Blind Placebo Controlled Trial. International Journal of Pharma Research and Health Sciences 2019; 7: 2952-2957
    CrossrefPubMedSearch in Google Scholar
  • 51 Sreelatha P, Jose WM. Efficacy of Carica papaya leaf extract in reducing treatment-delay secondary to chemotherapy-induced thrombocytopenia. Journal of Clinical and Diagnostic Research. 2020 14. XC09-12
    PubMedSearch in Google Scholar
  • 52 Solanki SG, Trivedi P. Evaluation of the efficacy of Carica papaya leaf extract on platelet counts in dengue patients. Journal of Advanced Scientific Research 2020; 11: 62-65
    PubMedSearch in Google Scholar
  • 53 Hettige S, Pushpakumara J, Wanigabadu LU. et al. Controlled Clinical Trial on Effect of ‘Carica Papaya’ Leaf Extract on Patients with Dengue Fever. Journal of Clinical Research and Medicine 2020; 3: 1-7
    PubMedSearch in Google Scholar
  • 54 Sathyapalan DT, Padmanabhan A, Moni M. et al. Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/μl) in adult dengue – Results of a pilot study. PLoS One 2020; 15: e0228699
    CrossrefPubMedSearch in Google Scholar
  • 55 Mohd Abd Razak MR, Mohmad Misnan N, Md Jelas NH. et al. The effect of freeze-dried Carica papaya leaf juice treatment on NS1 and viremia levels in dengue fever mice model. BMC complementary and alternative medicine 2018; 18: 1-3
    CrossrefPubMedSearch in Google Scholar
  • 56 Mohd Abd Razak MR, Norahmad NA, Md Jelas NH. et al. Preliminary study on the expression of endothelial cell biology related genes in the liver of dengue virus-infected mice treated with Carica papaya leaf juice. BMC research notes 2019; 12: 206
    CrossrefPubMedSearch in Google Scholar
  • 57 Joseph B, Sankarganesh P, Ichiyama K. et al. In vitro study on cytotoxic effect and anti-DENV2 activity of Carica papaya L. leaf. Frontiers in Life Science 2015; 8: 18-22
    CrossrefPubMedSearch in Google Scholar
  • 58 Chinnappan S, Shettikothanuru Ramachandrappa V, Tamilarasu K. et al. Inhibition of platelet aggregation by the leaf extract of Carica papaya during dengue infection: an in vitro study. Viral immunology 2016; 29: 164-168
    CrossrefPubMedSearch in Google Scholar
  • 59 Salim F, Abu NA, Yaakob H. et al. Interaction of Carica papaya L. leaves optimum extract on virus dengue infected cells. Sci Int 2018; 30: 437-441
    PubMedSearch in Google Scholar
  • 60 Sharma N, Mishra KP, Chanda S. et al. Evaluation of anti-dengue activity of Carica papaya aqueous leaf extract and its role in platelet augmentation. Archives of virology 2019; 164: 1095-1110
    CrossrefPubMedSearch in Google Scholar
  • 61 Galappaththi MO, Indeewari WMA, Abeykoon AMSB. et al. Antiviral activity of Carica papaya extract against experimental dengue virus 1 infection. Sri Lankan J Infect Dis 2021; 11: 8374
    PubMedSearch in Google Scholar
  • 62 Ma’rufah S, Saptawati L, Yuliasari FR. et al. Screening of Carica papaya L. And Psidium guajava leaves fraction as antiviral drug to dengue virus. Screening 2021; 44: 667-675
    PubMedSearch in Google Scholar
  • 63 Bere AW, Mulati O, Kimotho J. et al. Carica papaya leaf extract silver synthesized nanoparticles inhibit dengue type 2 viral replication in vitro. Pharmaceuticals 2021; 14: 718
    CrossrefPubMedSearch in Google Scholar
  • 64 Patil P, Alagarasu K, Chowdhury D. et al. In-vitro antiviral activity of Carica papaya formulations against dengue virus type 2 and chikungunya virus. Heliyon 2022; 8: e11879
    CrossrefPubMedSearch in Google Scholar
  • 65 Senthilvel P, Lavanya P, Kumar KM. et al. Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly. Bioinformation 2013; 9: 889
    CrossrefPubMedSearch in Google Scholar
  • 66 Rathnayake S, Madushanka A, Wijegunawardana NA. et al. In silico study of 5, 7-dimethoxy-coumarin and p-coumaric acid in Carica papaya leaves as dengue virus type 2 protease inhibitors. Proceedings 2020; 79: 11
    PubMedSearch in Google Scholar
  • 67 Madushanka A, Verma N, Freindorf M. et al. Papaya Leaf Extracts as Potential Dengue Treatment: An In-Silico Study. International Journal of Molecular Sciences 2022; 23: 12310
    CrossrefPubMedSearch in Google Scholar
  • 68 Banjan B, Krishnan D, Koshy AJ. et al. In-silico screening and identification of potential drug-like compounds for dengue-associated thrombocytopenia from Carica papaya leaf extracts. Journal of Biomolecular Structure and Dynamics. 2023 42. 5963-5981
    PubMedSearch in Google Scholar
  • 69 Dharmarathna SL, Wickramasinghe S, Waduge RN. et al. Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model. Asian Pacific Journal of Tropical Biomedicine 2013; 3: 720-724
    CrossrefPubMedSearch in Google Scholar
  • 70 Tahir N, Zaheer Z, Kausar S. et al. Prevention of Fall in Platelet Count By Carica papaya Leaf Juicei in carboplatin induced thrombocytopaenia in mice. Biomedica. 2014 30. 21-25
    PubMedSearch in Google Scholar
  • 71 Akhter T, Khan MI, Eva EO. Comparative evaluation of platelet augmentation activity of Carica papaya leaf juice and hydrocortisone in thrombocytopenic rats. Bangladesh journal of physiology and pharmacology 2015; 30: 32-40
    CrossrefPubMedSearch in Google Scholar
  • 72 Nandini C, Madhunapantula SV, Bovilla VR. et al. Platelet enhancement by Carica papaya L. leaf fractions in cyclophosphamide induced thrombocytopenic rats is due to elevated expression of CD110 receptor on megakaryocytes. Journal of ethnopharmacology 2021; 275: 114074
    CrossrefPubMedSearch in Google Scholar
  • 73 Zunjar V, Dash RP, Jivrajani M. et al. Antithrombocytopenic activity of carpaine and alkaloidal extract of Carica papaya Linn. leaves in busulfan induced thrombocytopenic Wistar rats. Journal of ethnopharmacology 2016; 181: 20-25
    CrossrefPubMedSearch in Google Scholar
  • 74 Anjum V, Arora P, Ansari SH. et al. Antithrombocytopenic and immunomodulatory potential of metabolically characterized aqueous extract of Carica papaya leaves. Pharmaceutical Biology 2017; 55: 2043-56.
    CrossrefPubMedSearch in Google Scholar
  • 75 Saraf M, Kavimandan B. Animal trials of Carica papaya leaf extracts for increasing platelet count. Indian J Public Health Res Dev 2017; 8: 782-787
    CrossrefPubMedSearch in Google Scholar
  • 76 Kumar MS, Shah MJ, Goyal M. et al. Evaluation of efficacy of Carica papaya leaf extracts to increase platelet count in hydroxyurea induced thrombocytopenia in Albino rats. International Journal of Basic & Clinical Pharmacology 2017; 7: 173-178
    CrossrefPubMedSearch in Google Scholar
  • 77 Utama SY. The effect of papaya leaf extract (Carica papaya l.) to the bleeding time on mice with trombositopenia. Jurnal Gizi dan Dietetik Indonesia (Indonesian Journal of Nutrition and Dietetics) 2018; 6: 133-138
    CrossrefPubMedSearch in Google Scholar
  • 78 Gheith I, El-Mahmoudy A. Hemogram and iron indices in renal anemia and the amelioration with Carica papaya leaf extract applied on albino rat model. Bioscience Reports 2019; 39: BSR20181699
    CrossrefPubMedSearch in Google Scholar
  • 79 Abdelrahim LM, Zain ZN, SNS AJ, Seman A, Mansur FA, Abdullah NS. The Potential Role Of Thrombopoietin And Il-6 In The Thrombocytosis Effect Of Carica papaya Leaves. International Journal of Research in Pharmaceutical Sciences. 2020 11. 1928-1934
    PubMedSearch in Google Scholar
  • 80 Bano S, Uzairullah MM, Tayyab Q. et al. The Papaya-Based Poly-Herbal Extract Eases Thrombocytopenia and Pyrexia in Rats. Journal of Hunan University Natural Sciences 2023; 50: 129-136
    PubMedSearch in Google Scholar
  • 81 Ojiako CM, Okoye EI, Oli AN. et al. Preliminary studies on the formulation of immune stimulating complexes using saponin from Carica papaya leaves. Heliyon 2019; 5: e01962
    CrossrefPubMedSearch in Google Scholar
  • 82 Jayasinghe CD, Gunasekera DS, De Silva N. et al. Mature leaf concentrates of Sri Lankan wild type Carica papaya Linn. modulates nonfunctional and functional immune responses of rats. BMC Complementary and Alternative Medicine 2017; 17: 1-4
    CrossrefPubMedSearch in Google Scholar
  • 83 Norahmad NA, Mohd Abd Razak MR, Mohmad Misnan N. et al. Effect of freeze-dried Carica papaya leaf juice on inflammatory cytokines production during dengue virus infection in AG129 mice. BMC complementary and alternative medicine 2019; 19: 1
    CrossrefPubMedSearch in Google Scholar
  • 84 Razak MR, Norahmad NA, Jelas NH. et al. Immunomodulatory activities of Carica papaya L. Leaf juice in a non-lethal, symptomatic dengue mouse model. Pathogens 2021; 10: 501
    CrossrefPubMedSearch in Google Scholar
  • 85 Kovendan K, Murugan K, Naresh Kumar A. et al. Bioefficacy of larvicdial and pupicidal properties of Carica papaya (Caricaceae) leaf extract and bacterial insecticide, spinosad, against chikungunya vector, Aedes aegypti (Diptera: Culicidae). Parasitology Research 2012; 110: 669-678
    CrossrefPubMedSearch in Google Scholar
  • 86 Malathi P, Vasugi SR. Evaluation of mosquito larvicidal effect of Carica papaya against Aedes Aegypti. International Journal of Mosquito Research 2015; 2: 21-24
    PubMedSearch in Google Scholar
  • 87 Ilham R, Lelo A, Harahap U. et al. The effectivity of ethanolic extract from papaya leaves (Carica papaya L.) as an alternative larvacide to Aedes spp. Open Access Macedonian Journal of Medical Sciences 2019; 7: 3395
    CrossrefPubMedSearch in Google Scholar
  • 88 Hayatie L, Biworo A, Suhartono E. Aqueous Extracts of Seed and Peel of Carica papaya against A Aedes Aegypti. Journal of Medical and Bioengineering 2015; 4: 417-421
    CrossrefPubMedSearch in Google Scholar
  • 89 Chandrasekaran R, Seetharaman P, Krishnan M. et al. Carica papaya (Papaya) latex: a new paradigm to combat against dengue and filariasis vectors Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae). 3 Biotech 2018; 8: 1
    CrossrefPubMedSearch in Google Scholar
  • 90 Cahyati WH, Asmara W, Umniyati SR. et al. Biolarvicidal effects of papaya leaves juice against Aedes aegypti Linn larvae. Journal of International Dental and Medical Research 2019; 12: 780-785
    PubMedSearch in Google Scholar
  • 91 Kellstein D, Fernandes L. Symptomatic treatment of dengue: should the NSAID contraindication be reconsidered?. Postgraduate Medicine 2019; 131: 109-116
    CrossrefPubMedSearch in Google Scholar
  • 92 Sah R, Siddiq A, Padhi BK. et al. Dengue virus and its recent outbreaks: current scenario and counteracting strategies. International Journal of Surgery 2023; 2: 10-97
    PubMedSearch in Google Scholar