Not ordinary antimalarial drugs: Madagascar plant decoctions potentiating the chloroquine action against Plasmodium parasites

Malaria mortality rates have fallen by 47% globally since 2000 and by 54% in the African region, but they are still a major problem. Malaria is caused by Plasmodium parasites, vectored to people through Anopheles mosquitoes, which mainly bite between dusk and dawn. Currently, a growing number of Plasmodium species and strains developed resistance to the most commonly used anti-malarial drugs. Chloroquine (CQ), the most commonly used anti-malarial drug, actually is not effective in a number of cases, and growing Plasmodium resistance has been already observed to artemisinin. New approaches are necessary to face this challenge. One of the strategies to overcome the drug resistance in different Plasmodium species is the search for compounds known as resistance-modifiers or chemosensitizers. These compounds may restore the CQ sensitivity in CQ-resistant strains of Plasmodium. The studies started from the knowledge that some Madagascar populations use decoctions of some local plants in association with low doses of CQ to complement the CQ action against chronic malaria. In such way, resistance insurgence is lowered, as well as collateral effects. Phytochemical analyses on twelve plant species commonly used by local populations to treat malaria evidenced the presence of complex alkaloids, which showed in vitro and/or in vivo efficacy against CQ-resistant Plasmodium strains, attesting the potential use of the mix of CQ and medicinal plant preparations or compounds therein present. The approach, in accordance with recent tendencies on multidrug resistance control, is based on mixtures of natural products and classic antimalarial drugs, with a relevant coincidence between the ethnobotanical reports and the scientific evidence.