Natural products for the control of malaria
Malar J. 2011 Mar 15;10 Suppl 1:S1
PubMed recently posted several articles from a 2011 supplement to Malaria Journal devoted to natural products for the control of malaria, so I’ve taken the opportunity to look at the entire issue.
Edited by Hagai Ginsburg of The Hebrew University of Jerusalem, and funded with contributions from the African Network for Drugs & Diagnostics Innovation, Department of Primary Health Care at University of Oxford, Institut de Recherche pour le Développement, MMV – Medicines for Malaria Venture and University of Cape Town, the supplement surveys a number of topics related to the use of natural compounds in the development of antimalarial treatments.
I’ll address the articles one at a time, starting with the editor’s introduction.
I. A call for using natural compounds in the development of new antimalarial treatments – an introduction
Ginsburg H, Deharo E
Malar J. 2011 Mar 15;10 Suppl 1:S1
PubMed Central PMCID: PMC3059457
In this introduction, supplement editor Hagai Ginsburg and Eric Deharo of the Université de Toulouse and the Institut de Recherche pour le Développement argue for a revisiting of old approaches to the development of antimalarial drugs.
From the abstract:
“Natural compounds, mostly from plants, have been the mainstay of traditional medicine for thousands of years. They have also been the source of lead compounds for modern medicine, but the extent of mining of natural compounds for such leads decreased during the second half of the 20th century. The advantage of natural compounds for the development of drugs derives from their innate affinity for biological receptors. Natural compounds have provided the best anti-malarials known to date. Recent surveys have identified many extracts of various organisms (mostly plants) as having antiplasmodial activity. Huge libraries of fractionated natural compounds have been screened with impressive hit rates. Importantly, many cases are known where the crude biological extract is more efficient pharmacologically than the most active purified compound from this extract. This could be due to synergism with other compounds present in the extract, that as such have no pharmacological activity. Indeed, such compounds are best screened by cell-based assay where all potential targets in the cell are probed and possible synergies identified. Traditional medicine uses crude extracts. These have often been shown to provide many concoctions that deal better with the overall disease condition than with the causative agent itself. Traditional medicines are used by ~80 % of Africans as a first response to ailment. Many of the traditional medicines have demonstrable anti-plasmodial activities. It is suggested that rigorous evaluation of traditional medicines involving controlled clinical trials in parallel with agronomical development for more reproducible levels of active compounds could improve the availability of drugs at an acceptable cost and a source of income in malaria endemic countries.”
For malaria research, Ginsburg and Deharo propose a shift in the drug discovery paradigm from ‘finding new-entity drugs’ to ‘combining existing agents’. Reviewing the current literature on drug leads for novel plant-based antimalarials, they note a bias against studying the biological activity of crude extracts and favoring the screening of purified compounds – potentially missing the effect of synergistic combinations that might have arisen over the natural history of the plant-based therapy. They also address significant limitations of the prevailing model of rational drug development, in which a thorough understanding of a disease’s pathogenesis and the mechanism of a therapy’s action is the primary, if not exclusive, driver of discovery:
“Testing the effects of extracts usually doesn’t divulge the drug target or its mode of action. But if the extract is working well is it really important as to know the precise mode of action? In the context of anti-malarials, it is relevant to underscore the fact that till this very day, the mechanism of action of two of the most efficient drugs derived from traditional medicine, artemisinin and quinine, is still debatable.”
In their conclusion, Ginsburg and Deharo introduce a third key theme for this supplement, a review of scientific and pharmacological evidence to provide a “basis for further development of ethnic/traditional medicine as a valid, cheap and locally-available means to treat malaria.”
Read the complete article at PubMed Central.
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