In Vivo and in Silico Antimalaria Activity of Carica Papaya Leaves from Bali
Abstract
Objective: to determine the antimalarial effect of Carica papaya leaves and to examine the affinity and interaction models of selected Carica papaya compounds with a Plasmodium falcipain-2, which has an important role in parasite development.
Material and Methods: The design of the study was in vivo and in silico. This in vivo study used Peter’s four-day suppressive test, and it was conducted using 18 mice to evaluate the antimalarial effect of Carica papaya leaves. Parasitemia levels were analyzed statistically using one-way analysis of variance (ANOVA). The screening of Carica papaya compounds was carried out in silico using AutoDock 4.2 software to examine their antimalarial activity. The molecular structure of the isoquercetin, falcipain-2, was downloaded from the Protein Data Bank (PDB ID: 3BPF). The docking method was valid if the root mean square deviation (RMSD) was less than 2 Ångströms.
Results: The in vivo results showed that the administration of ethanol extracts of Carica papaya leaves at doses of 100 and 1,000 mg/kg BW inhibited the increase in parasitemia levels, which were 82.1% and 83.8% on the second day and 95.9% and 95.9% on the third day, respectively. Meanwhile, in silico results showed that quercetin, isoquercetin, carpain, and caricaxanthin exhibited lower energies than the native ligand. Conversely, violaxanthin showed a positive energy value.
Conclusion: In vivo and in silico findings suggest that Carica papaya leaf extract at 100 and 1,000 mg/kg BW has antimalarial activity, and carpaine demonstrates promising in silico activity against falcipain-2, warranting further validation.
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World Health Organization. World Malaria Report 2023 [homepage on the Internet]. Geneva: WHO; 2023 [cited 2023 Dec 28]. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria- report-2023
Hanboonkunupakarn B, Tarning J, Pukrittayakamee S, Chotivanich K. Artemisinin resistance and malaria elimination: Where are we now? Front Pharmacol 2022;13:1-10
Hariono M, Julianus J, Djunarko I, Hidayat I, Adelya L, Indayani F, et al. The future of Carica papaya leaf extract as an herbal medicine product. Molecules 2021;26:1-20
Sharma A, Sharma R, Sharma M, Kumar M, Barbhai MD, Lorenzo JM, et al. Carica papaya L. Leaves: Deciphering its antioxidant bioactives, biological activities, innovative products, and safety aspects. Oxid Med Cell Longev 2022;2022:1-20.
Lim XY, Chan JSW, Japri N, Lee JC, Tan TYC. Carica papaya L. Leaf: A systematic scoping review on biological safety and herb-drug interactions. Evid Based Complement Alternat Med 2021;2021:1-21.
Belete TM. Recent progress in the development of new antimalarial drugs with novel targets. Drug Des Devel Ther 2020;14:3875-89.
Agu PC, Afiukwa CA, Orji OU, Ezeh EM, Ofoke IH, Ogbu CO, et al. Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci Rep 2023;13:1-18.
Rosenthal PJ. Falcipain cysteine proteases of malaria parasites: An update. Biochim Biophys Acta Proteins Proteom 2020;1868:1-3.
Pandey KC, Dixit R. Structure-function of falcipains: malarial cysteine proteases. J Trop Med 2012;2012:1-11.
Arifin WN, Zahiruddin WM. Sample size calculation in animal studies using resource equation approach. Malays J Med Sci 2017;24:101-5.
Cahyaningsih U, Sa’diah S, Syafii W, Sari RK, Maring AJ, Nugraha AB. Antimalarial efficacy of aqueous extract of Strychnos ligustrina and its combination with Dihydroartemisinin and Piperaquine Phosphate (DHP) against Plasmodium berghei infection. Korean J Parasitol 2022;60:339-344.
Budiapsari PI, Jaya PK, Dewi PM, Laksemi DA, Horng JT. Effect of moringa extract on parasitemia, monocyte activation and organomegaly among Mus musculus infected by Plasmodium berghei ANKA. Narra J 2024;4:1-7.
Buck E, Finnigan NA. Malaria. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025.
Taychaworaditsakul W, Saenjum C, Lumjuan N, Chawansuntati K, Sawong S, Jaijoy K, et al. Safety of oral Carica papaya L. leaf 10% ethanolic extract for acute and chronic toxicity tests in Sprague Dawley rats. Toxics 2024;12:1-20.
Fatmawaty F, Rosmalena R, Amalia A, Syafitri I, Prasasty VD. Antimalarial effect of Flamboyant (Delonix regia) bark and Papaya (Carica papaya L.) leaf ethanolic extracts against Plasmodium berghei in mice. Biomed Pharmacol J 2017;10:1081-9.
Arifuddin M, Bone M, Rusli R, Kuncoro H, Ahmad I, Rijai L. Antimalarial activity of heme polymerization inhibition of guava (Psidium guajava) and Carica papaya leaf ethanol extract. J Sci Ibnu Sina 2019;4:235-43.
Atanu FO, Idih FM, Nwonuma CO, Hetta HF, Alamery S, El-Saber Batiha G. Evaluation of antimalarial potential of extracts from Alstonia boonei and Carica Papaya in Plasmodium berghei-infected mice. Evid Based Complement Alternat Med 2021;2021:1-11.
Yang L, Wen KS, Ruan X, Zhao YX, Wei F, Wang Q. Response of plant secondary metabolites to environmental factors. Molecules 2018;23:1-26.
Susanti NMP, Dewi LPMK, Bhadreswara IGRW. In silico study of antidiabetic activity and toxicity of trans-anethole, fenchone and estragole. J Pharm Sci & Appl 2024;6:40-8
Yang JF, Wang F, Chen YZ, , Hao GF, Yang GF. LARMD: integration of bioinformatic resources to profile ligand-driven protein dynamics with a case on the activation of estrogen receptor. Brief. Bioinform 2020;21:2206–18.
Vanaja P, Moorthy NSHN, Rajpoot VS, Rao H, Goswami RK, Subash P, et al. Metabolite profiling, antimalarial potentials of Schleichera oleosa using LC-MS and GC-MS: in vitro, molecular docking and molecular dynamics. Front Mol Biosci 2025;12:1543939. doi: 10.3389/fmolb.2025.1543939.
Nkungli NK, Fouegue ADT, Tasheh SN, Bine FK, Hassan AU, Ghogomu JN. In silico investigation of falcipain-2 inhibition by hybrid benzimidazole-thiosemicarbazone antiplasmodial agents: A molecular docking, molecular dynamics simulation, and kinetics study. Mol Divers 2024;28:475-96. doi: 10.1007/s11030-022-10594-3.
A’yun Q dan Laily AN. The phytochemical analysis of papaya leaf (Carica papaya L) at the research center of various bean and tuber crops kendalpayak, malang. Proceeding Indonesian National Seminar on Conservation and Utilization of Natural Resources 2015:134-7.
Kumaree KK, Anthikapalli NVA and Prasansuklab A. In silico screening for potential inhibitors from the phytocompounds of Carica papaya against Zika virus NS5 protein. F1000Research 2024;12:1-31.
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