Most research for antimalarial new drugs is only focused on direct activity against Plasmodium species. But attention to ethnomedical information gathered by Monteiro da Silva suggests that other effects should be investigated. For example, some plants are referred to enhance the action of other herbs, which can indicate an increase on permeability of the Plasmodium membrane to antiparasitic substances, or an inhibition of pump mechanisms of eliminating the drugs[58,59]. Considering that one of the common mechanisms of drugs resistance is the reduction of permeability, the development of drugs that enhance parasite permeability could be of valuable help in the treatment of infectious diseases[60,61]. Other possible mechanism of action is interference with parasite enzymes used for protection against antiparasitic drugs[62].
Some plants with noticeable ethnopharmacological use in malaria showed only weak or even no activity against Plasmodium in vitro[55]. For example, Mikania glomerata, Melampodium divaricatum, Galipea multiflora, Aspidosperma polyneuron, and Coutarea hexandra had their antimalarial activity confirmed by clinical observations of medical doctors (Table 1), an information that yields a high probability of accuracy.
Some authors have underestimated the traditional plants used for malaria based exclusively on low activity against Plasmodium in vitro or in animal models[55]. This can be a mistake of strategy or even methodology.
There are many explanations for the absence of in vitro activity of an effective antimalarial drug. As an example, the active principle could be formed by hepatic metabolism, or as a result of transformation by gut bacteria. Other possible mechanisms of action include immunomodulation or interference with the invasion of new red blood cells by parasites, which can be species specific. Therefore studies in human subjects, as well as the observance of ethnomedical detailed data, are urged in order to exclude or confirm the activity of herbs traditionally used to treat malaria.
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