Plant-derived secondary metabolites for malaria treatment: extraction, mechanisms, and therapeutic potential

Medicinal plants have long been used as a primary healthcare resource for treating malaria and other diseases globally. Malaria, caused by Plasmodium species, remains a serious health threat, with the World Health Organization reporting that over 40 % of the global population lives in malaria-endemic regions. The rise of drug-resistant strains has further complicated treatment efforts, necessitating the search for new therapeutic agents. This review emphasizes the antimalarial potential of plant-derived secondary metabolites, which exhibit diverse pharmacological activities. Several compounds, such as ceramicine R (IC₅₀ = 2.80 μM), knipholone clooxanthrone (IC₅₀ = 14.58 μM for D6 and 9.42 μM for W2), joziknipholone A (IC₅₀ = 0.17 μM), joziknipholone B (IC₅₀ = 0.26 μM), and cajachalcone (IC₅₀ = 7.4 μM), have shown potent activity against Plasmodium falciparum. Data were collected from Web of Science, PubMed, Scopus, Google Scholar, and Science Direct. A total of 34 medicinal plants were identified, along with details on extraction techniques and factors influencing metabolite efficacy. Key secondary metabolites include alkaloids, flavonoids, terpenoids, and their derivatives (e.g., quinine, artemisinin, quercetin, chalcones). This review highlights their mechanisms of action and their promise as templates for developing novel drugs to combat both drug-sensitive and drug-resistant malaria strains.