Vet World Vol.18 June-2025 Article - 22
Research Article
Veterinary World, 18(6): 1644-1659
https://doi.org/10.14202/vetworld.2025.1644-1659
In vitro and in silico investigations of Propolis-derived phytochemicals as potential inhibitors of Plasmodium falciparum
, Md. Nazmul Hasan1 , Rachasak Boonhok2 , Suthinee Sungkanu2 , Yutatirat Singhaboot3 , Afsana Amin Shorna4 , Anamul Hasan4 , Kesinee Chotivanich3 , Polrat Wilairatana3 , Abolghasem Siyadatpanah5 , Roghayeh Norouzi6 , Imran Sama-ae7,8 , Watcharapong Mitsuwan9 , Alok K. Paul10 , Maria de Lourdes Pereira11,12 , Shanmuga S. Sundar13 , Tooba Mahboob14 , Christophe Wiart15 , Ryan V. Labana16,17 , Siriphorn Chimplee18 , and Veeranoot Nissapatorn19,20 1. Laboratory of Pharmaceutical Biotechnology and Bioinformatics, Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, Bangladesh.
2. School of Allied Health Sciences, Research Excellence Center for Innovation and Health Products (RECIHP) and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat, Thailand. 3.
3. Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
4. Department of Biotechnology and Genetic Engineering, University of Development Alternative, Dhaka, Bangladesh.
5. Department of Parasitology, School of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran.
6. Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
7. Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, Thailand.
8. Center of Excellence Research for Melioidosis and Microorganisms (CERMM), Walailak University, Nakhon Si Thammarat, Thailand.
9. Akkhraratchakumari Veterinary College, Walailak University, Nakhon Si Thammarat, Thailand.
10. School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS, Australia.
11. CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal.
12. Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
13. Department of Biotechnology, AVIT, Vinayaka Mission’s Research Foundation (DU), Chennai Campus, Chennai, Tamil Nadu, India.
14. Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia.
15. Institute for Tropical Biology & Conservation, University Malaysia Sabah, Malaysia.
16. Center for Health Sciences, Research Institute for Science and Technology, Polytechnic University of the Philippines, Sta. Mesa, Manila, Philippines.
17. Department of Biology, College of Science, Polytechnic University of the Philippines, Sta. Mesa, Manila, Philippines.
18. General Education Department, School of Languages and General Education, Walailak University, Nakhon Si Thammarat, Thailand.
19. School of Allied Health Sciences, Research Excellence Center for Innovation and Health Products (RECIHP) and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat, Thailand.
20. Futuristic Science Research Center, School of Science, Walailak University, Nakhon Si Thammarat, Thailand.
Background and Aim: Malaria continues to pose a global health challenge, exacerbated by the emergence of drug-resistant strains of Plasmodium falciparum. This study aimed to evaluate the anti-Plasmodium potential of Propolis extracts collected from various Iranian regions and to characterize the molecular interactions of their bioactive phytochemicals with P. falciparum lactate dehydrogenase (PfLDH), a key enzyme in parasite glycolysis.
Materials and Methods: The anti-Plasmodium activity of ethanol-extracted Propolis was assessed against P. falciparum NF54 using the SYBR Green I fluorescence assay. Gas chromatography-mass spectrometry (GC-MS) analysis identified major phytochemicals in the most active extract. Molecular docking and 100-ns molecular dynamic (MD) simulations were performed to evaluate the binding affinity and stability of selected compounds (tectochrysin and galangin) against PfLDH in both holo (Protein Data Bank [PDB] ID: 1LDG) and apo (PDB ID: 2X8L) forms.
Results: Propolis collected from Kermanshah city exhibited the highest anti-Plasmodium activity (IC50 = 6.69 ± 1.44 μg/mL). GC-MS analysis identified tectochrysin and galangin as major constituents. Molecular docking revealed strong binding affinities of tectochrysin (−7.8 kcal/mol) and galangin (−7.5 kcal/mol) to PfLDH, surpassing the binding energies of standard antimalarial drugs (chloroquine and quinine). MD simulations confirmed the stability of tectochrysin and galangin within the PfLDH active sites, with favorable root mean square deviation, root mean square fluctuation, gyration, solvent-accessible surface area, molecular surface area, and polar surface area profiles, indicating persistent and stable protein-ligand interactions throughout the simulation.
Conclusion: The findings support the promising anti-Plasmodium potential of Propolis-derived compounds, particularly tectochrysin and galangin, as novel PfLDH inhibitors. Their potential applicability in transdisciplinary anti-parasitic therapy across human and veterinary medicine warrants further in vivo validation and clinical investigations.
Keywords: anti-malarial candidates, galangin, lactate dehydrogenase, molecular docking, molecular dynamics, Plasmodium falciparum, Propolis extract, tectochrysin
How to cite this article: Khan DA, Hasan MN, Boonhok R, Sungkanu S, Singhaboot Y, Shorna AA, Hasan A, Chotivanich K, Wilairatana P, Siyadatpanah A, Norouzi R, Sama-ae I, Mitsuwan W, Paul AK, Pereira ML, Sundar SS, Mahboob T, Wiart C, Labana RV, Chimplee S, and Nissapatorn V (2025) In vitro and in silico investigations of Propolis-derived phytochemicals as potential inhibitors of Plasmodium falciparum, Veterinary World, 18(6): 1644-1659.
Received: 20-05-2025 Accepted: 15-05-2025 Published online: 19-06-2025
Corresponding author: E-mail:
DOI: 10.14202/vetworld.2025.1644-1659
Copyright: Khan, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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