Abstract

Malaria, a disease of great concern, has seen a rise in drug-resistant strains, leading to increased morbidity and mortality rates. Repositioning or repurposing existing bioactive natural products is an alternative and short-term strategy to reduce the time and expense of developing new medications. This study aimed to evaluate 12 Thai herbs and their major constituents, assessing their lactate dehydrogenase inhibitory activity as a single agent or in combination with artesunate against the chloroquine-resistant Plasmodium falciparum K1 strain. The study revealed that the ethanolic extracts of leaves of Garcinia cowa Roxb., Clusiaceae, heartwood of Caesalpinia sappan L., Fabaceae, peel of G. mangostana L., Clusiaceae, fruit of Punica granatum L., Lythraceae, and rhizome of Zingiber cassumunar Roxb., Zingiberaceae exhibited anti-Plasmodium falciparum lactate dehydrogenase activity at concentrations < 10 µg/ml. Furthermore, active constituents, including punicalagin, β-mangostin, α-mangostin, ellagic acid, γ-mangostin, and plumbagin, exhibited anti-P. falciparum lactate dehydrogenase activity at concentrations of 2.10 ± 0.68, 2.14 ± 0.85, 2.58 ± 0.46, 4.57 ± 0.11, 4.89 ± 0.85, and 8.24 ± 0.53 µg/ml, respectively. Punicalagin and ellagic acid, among the active compounds, showed the most potent anti-P. falciparum lactate dehydrogenase activities without cytotoxicity. Furthermore, the synergistic study revealed that the two-drug combinations had an additive antimalarial interaction effect. Ellagic acid and artesunate showed the best synergistic profiles and should be further tested for drug-like properties. Graphical Abstract: (Figure presented.)