Profiling plant extracts with antimalarial bloodstage activity using metabolomics

Natural products and their derivatives have historically contributed significantly to malaria treatment. However, despite their promising structural diversity, it is challenging to study and profile such compounds, especially when adapting extracts or fractions from traditional bioactivity-guided isolation methods. Metabolomics is a robust approach that can be used to profile the mode of action (MoA) of antiplasmodial compounds, but it has seldom been applied to complex matrices such as plant extracts. In this study, plant extracts and their active natural compounds were studied through LC-MS metabolomics to evaluate their MoA. Artemisia annua, Cinchona officinalis and Poupartia borbonica Gmel were found to be good starting points for profiling but were not as conclusive as using purified artemisinin, quinine and poupartone-B. Our findings suggest that metabolomics is a viable tool to profile plant extracts and natural compounds with promising antiplasmodial activity and should be incorporated as a standard screening method in drug discovery.