Metabolite Profiling of Artemisia Afra and Artemisia Annua Extracts Reveals Divergent Effects on Plasmodium Falciparum

Background: Artemisia spp. have been used for millennia in traditional medicine to treat a variety of ailments, including malaria. Extracts of Artemisia afra and A. annua remain widely used throughout Africa for healthcare purposes, notably to prevent and/or treat malaria. However, the modes of action of these plant extracts remain unclear, with contradictory reports regarding the presence and role of artemisinin in both plants.

Purpose: The aim of this study was to identify differences in the antimalarial mode of action of A. afra and A. annua by measuring their phenolic profiles and comparing their effect on parasite metabolism in vitro.

Methods: In this work, we analyzed the phenolic profile of A. afra and A. annua extracts through high-performance liquid chromatography (HPLC), detected and quantified artemisinin through HPLC and mass spectrometry (MS), and performed comparative HPLC-MS metabolomic analysis on in vitro-cultured Plasmodium falciparum trophozoites to elucidate the potential modes of action of these plant extracts.

Results: A. afra contained only trace amounts of artemisinin and elicited a different parasite metabolic response compared to A. annua, which contained significantly more artemisinin and correlated closely with the parasite response profile elicited by purified artemisinin. A. annua impacted parasite glutathione metabolism in agreement with the established redox activity of artemisinin, while A. afra had an effect on lipid precursors.

Conclusions: This study reveals that A. afra and A. annua have divergent effects on Plasmodium falciparum metabolism and provides support for ongoing efforts exploring the use of A. afra for the treatment of malaria.