Amatul Hamizah Ali, Siti Nur Hidayah Jamil, Wan Rozianoor Mohd Hassan, Hani Kartini Agustar, Shevin Feroz Rizal, Lam Su Datt, Noor Embi, Hasidah Mohd Sidek, Rusliza Basir, Lau Yee Ling, Jalifah Latip
Curcumin, a polyphenolic compound exhibits various bioactivities, including antimalarial and anti-inflammatory effects. This study investigated the long-term antimalarial effects of curcumin through in vivo experiments using Plasmodium berghei NK65-infected mice, complemented by in vitro and in silico analyses targeting the plasmodial GSK3 protein. Through in vitro , the antimalarial activity of curcumin was assessed on P. falciparum K1 (multi-drug resistant strain) and 3D7 (sensitive strain) as well as P. knowlesi A1H1 of Plasmodium lactate dehydrogenase (pLDH) assay, alongside cytotoxic effects on Vero cells using the MTT assay. Curcumin demonstrated its bioactivity to disrupt the parasite’s growth and replication based on the effective inhibition on both P. falciparum (3D7 EC50=8.11 µM; K1 EC50=31.21 µM) and P. knowlesi (EC50=4.51 µM). Molecular docking studies explored curcumin's interaction with the ATP-binding pocket of P. falciparum glycogen synthase kinase-3 (PfGSK3) with favourable binding affinity (-8.72 kcal/mol), revealing it potential as a selective inhibitor. Further, in vivo experiments validated curcumin's immunomodulatory activities and therapeutic effects in P. berghei -infected mice. Prolonged curcumin treatment has shown to significantly reduce the parasitaemia compared to the controls. Cytokine profiling via ELISA showed enhanced levels of anti-inflammatory cytokines (IL-10, IL-4) and decreased pro-inflammatory markers (TNF-α, IFN-γ), mitigating systemic inflammation associated with malaria. Histopathological analysis revealed reduction of tissue damage in the curcumin-treated mice, including decreasing parasite sequestration, inflammatory cell infiltration, hepatocyte necrosis and hemorrhages. This study highlights curcumin's potentials in inhibiting PfGSK3, regulating immune responses, and attenuating tissue damage which support its therapeutic role against malarial infection. © 2026 Elsevier B.V.
Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), Selangor, Bangi, 43600, Malaysia; International Joint Department of Materials Science and Engineering between, National University of Malaysia and Gifu University, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan; School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Shah Alam, 40450, Malaysia; Human Genetic and Biochemistry, Research Nexus of UiTM (ReNeU), Universiti Teknologi MARA, Selangor, Shah Alam, 40450, Malaysia; Department of Earth Science and Environment, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), Selangor, Bangi, 43600, Malaysia; Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), Selangor, Bangi, 43600, Malaysia; Department of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), Selangor, Bangi, 43600, Malaysia; Pharmacology Unit, Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Serdang, 43400, Malaysia; Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; Smart Material and Sustainable Product Innovation (SMatSPIn) Research, Universiti Kebangsaan Malaysia, Selangor, Bangi, 43600, Malaysia; Department of Chemistry, Universitas Negeri Malang, Jl. Semarang No. 5 Malang, Indonesia
