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Published in: Malaria Journal 1/2011

Open Access 01-12-2011 | Reviews

A “reverse pharmacology” approach for developing an anti-malarial phytomedicine

Authors: Merlin L Willcox, Bertrand Graz, Jacques Falquet, Chiaka Diakite, Sergio Giani, Drissa Diallo

Published in: Malaria Journal | Special Issue 1/2011

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Abstract

A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.
Literature
1.
go back to reference WHO: Guidelines for the treatment of malaria. 2010, Geneva: World Health Organisation, 2 WHO: Guidelines for the treatment of malaria. 2010, Geneva: World Health Organisation, 2
2.
go back to reference Dondorp AM, Yeung S, White L, Nguon C, Day NPJ, Socheat D, von Seidlein L: Artemisinin resistance: current status and scenarios for containment. Nature Reviews Microbiology. 2010, 8: 272-280. 10.1038/nrmicro2385.CrossRefPubMed Dondorp AM, Yeung S, White L, Nguon C, Day NPJ, Socheat D, von Seidlein L: Artemisinin resistance: current status and scenarios for containment. Nature Reviews Microbiology. 2010, 8: 272-280. 10.1038/nrmicro2385.CrossRefPubMed
3.
go back to reference Nwaka S, Hudson A: Innovative lead discovery strategies for tropical diseases. Nature Reviews Drug Discovery. 2006, 5: 941-955. 10.1038/nrd2144.CrossRefPubMed Nwaka S, Hudson A: Innovative lead discovery strategies for tropical diseases. Nature Reviews Drug Discovery. 2006, 5: 941-955. 10.1038/nrd2144.CrossRefPubMed
4.
go back to reference Nwaka S, Ramirez B, Brun R, Maes L, Douglas F, Ridley R, Nwaka S, Ramirez B, Brun R, Maes L: Advancing drug innovation for neglected diseases-criteria for lead progression. PLoS Neglected Tropical Diseases [electronic resource]. 2009, 3: e440-10.1371/journal.pntd.0000440.CrossRef Nwaka S, Ramirez B, Brun R, Maes L, Douglas F, Ridley R, Nwaka S, Ramirez B, Brun R, Maes L: Advancing drug innovation for neglected diseases-criteria for lead progression. PLoS Neglected Tropical Diseases [electronic resource]. 2009, 3: e440-10.1371/journal.pntd.0000440.CrossRef
5.
go back to reference DiMasi JA, Hansen RW, Grabowski HG: The price of innovation: new estimates of drug development costs. Journal of Health Economics. 2003, 22: 151-185. 10.1016/S0167-6296(02)00126-1.CrossRefPubMed DiMasi JA, Hansen RW, Grabowski HG: The price of innovation: new estimates of drug development costs. Journal of Health Economics. 2003, 22: 151-185. 10.1016/S0167-6296(02)00126-1.CrossRefPubMed
6.
go back to reference Lei SH-l, Bodeker G: Changshan (Dichroa febrifuga). Ancient Febrifuge And Modern Antimalarial: Lessons For Research From A Forgotten Tale. Traditional Medicinal Plants and Malaria. Edited by: Willcox M, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press Lei SH-l, Bodeker G: Changshan (Dichroa febrifuga). Ancient Febrifuge And Modern Antimalarial: Lessons For Research From A Forgotten Tale. Traditional Medicinal Plants and Malaria. Edited by: Willcox M, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press
7.
go back to reference Patwardhan B, Mashelkar RA, Patwardhan B, Mashelkar RA: Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?. Drug Discovery Today. 2009, 14: 804-811. 10.1016/j.drudis.2009.05.009.CrossRefPubMed Patwardhan B, Mashelkar RA, Patwardhan B, Mashelkar RA: Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?. Drug Discovery Today. 2009, 14: 804-811. 10.1016/j.drudis.2009.05.009.CrossRefPubMed
8.
go back to reference Graz B, Falquet J, Elisabetsky E: Ethnopharmacology, sustainable development and cooperation: The importance of gathering clinical data during field surveys. Journal of Ethnopharmacology. 2010, 130: 635-638. 10.1016/j.jep.2010.04.044.CrossRefPubMed Graz B, Falquet J, Elisabetsky E: Ethnopharmacology, sustainable development and cooperation: The importance of gathering clinical data during field surveys. Journal of Ethnopharmacology. 2010, 130: 635-638. 10.1016/j.jep.2010.04.044.CrossRefPubMed
9.
go back to reference Graz B, Diallo D, Falquet J, Willcox M, Giani S: Screening of traditional herbal medicine: first, do a retrospective study, with correlation between diverse treatments used and reported patient outcome. Journal of Ethnopharmacology. 2005, 101: 338-339. 10.1016/j.jep.2005.07.008.CrossRefPubMed Graz B, Diallo D, Falquet J, Willcox M, Giani S: Screening of traditional herbal medicine: first, do a retrospective study, with correlation between diverse treatments used and reported patient outcome. Journal of Ethnopharmacology. 2005, 101: 338-339. 10.1016/j.jep.2005.07.008.CrossRefPubMed
10.
go back to reference Diallo D, Graz B, Falquet J, Traore AK, Giani S, Mounkoro PP, Berthe A, Sacko M, Diakite C: Malaria treatment in remote areas of Mali: use of modern and traditional medicines, patient outcome. Trans R Soc Trop Med Hyg. 2006, 100: 515-520. 10.1016/j.trstmh.2005.08.003.CrossRefPubMed Diallo D, Graz B, Falquet J, Traore AK, Giani S, Mounkoro PP, Berthe A, Sacko M, Diakite C: Malaria treatment in remote areas of Mali: use of modern and traditional medicines, patient outcome. Trans R Soc Trop Med Hyg. 2006, 100: 515-520. 10.1016/j.trstmh.2005.08.003.CrossRefPubMed
11.
go back to reference WHO: Guidelines for the treatment of malaria. WHO/HTM/MAL/2006.1108. 2006, Geneva: WHO WHO: Guidelines for the treatment of malaria. WHO/HTM/MAL/2006.1108. 2006, Geneva: WHO
12.
go back to reference Diallo D, Diakite C, Mounkoro PP, Sangare D, Graz B, Falquet J, Giani S: [Knowledge of traditional healers on malaria in Kendi (Bandiagara) and Finkolo (Sikasso) in Mali ]. Mali Med. 2007, 22: 1-8.PubMed Diallo D, Diakite C, Mounkoro PP, Sangare D, Graz B, Falquet J, Giani S: [Knowledge of traditional healers on malaria in Kendi (Bandiagara) and Finkolo (Sikasso) in Mali ]. Mali Med. 2007, 22: 1-8.PubMed
13.
go back to reference Benoit-Vical F, Soh PN, Salery M, Harguem L, Poupat C, Nongonierma R: Evaluation of Senegalese plants used in malaria treatment: focus on Chrozophora senegalensis. J Ethnopharmacol. 2008, 116: 43-48. 10.1016/j.jep.2007.10.033.CrossRefPubMed Benoit-Vical F, Soh PN, Salery M, Harguem L, Poupat C, Nongonierma R: Evaluation of Senegalese plants used in malaria treatment: focus on Chrozophora senegalensis. J Ethnopharmacol. 2008, 116: 43-48. 10.1016/j.jep.2007.10.033.CrossRefPubMed
14.
go back to reference WHO: Expert Committee on specifications for pharmaceutical preparations: Thirty-fourth report. 1996, Geneva: World Health Organisation WHO: Expert Committee on specifications for pharmaceutical preparations: Thirty-fourth report. 1996, Geneva: World Health Organisation
15.
go back to reference WHO: Guidelines for the Appropriate Use of Herbal Medicines. 1998, Manila: WHO Regional Office for the Western Pacific WHO: Guidelines for the Appropriate Use of Herbal Medicines. 1998, Manila: WHO Regional Office for the Western Pacific
16.
go back to reference Katende AB, Ssegawa P, Birnie A: Wild food plants and mushrooms of Uganda. 1999, Nairobi: Regional Land Management Unit, Sida Katende AB, Ssegawa P, Birnie A: Wild food plants and mushrooms of Uganda. 1999, Nairobi: Regional Land Management Unit, Sida
17.
go back to reference WHO: General guidelines for methodologies on research and evaluation of traditional medicine. 2000, Geneva: World Health Organisation WHO: General guidelines for methodologies on research and evaluation of traditional medicine. 2000, Geneva: World Health Organisation
18.
go back to reference Willcox ML, Gamaniel SK, Matsabisa MG, Randriasamimanana JR, Wambebe CON, Rasoanaivo P: Guidelines for the pre-clinical evaluation of the safety of traditional herbal antimalarials. Traditional Medicinal Plants and Malaria. Edited by: Willcox M, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press Willcox ML, Gamaniel SK, Matsabisa MG, Randriasamimanana JR, Wambebe CON, Rasoanaivo P: Guidelines for the pre-clinical evaluation of the safety of traditional herbal antimalarials. Traditional Medicinal Plants and Malaria. Edited by: Willcox M, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press
21.
go back to reference WHO: WHO Monographs on selected medicinal plants. 1999, Geneva: World Health Organisation WHO: WHO Monographs on selected medicinal plants. 1999, Geneva: World Health Organisation
22.
go back to reference Barnes J, Anderson L, Phillipson J: Herbal Medicines. 2007, London: Pharmaceutical Press, 3 Barnes J, Anderson L, Phillipson J: Herbal Medicines. 2007, London: Pharmaceutical Press, 3
23.
go back to reference Frohne D, Pfände H: Poisonous Plants: A Handbook for Doctors, Pharmacists, Toxicologists, Biologists and Veterinarians. 2005, Timber Press, 2 Frohne D, Pfände H: Poisonous Plants: A Handbook for Doctors, Pharmacists, Toxicologists, Biologists and Veterinarians. 2005, Timber Press, 2
24.
go back to reference Mills S, Bone K: The Essential Guide to Herbal Safety. 2005, St Louis, Missouri: Elsevier Churchill Livingstone Mills S, Bone K: The Essential Guide to Herbal Safety. 2005, St Louis, Missouri: Elsevier Churchill Livingstone
25.
go back to reference Verma SK, Dev G, Tyagi AK, Goomber S, Jain GV: Argemone mexicana poisoning: autopsy findings of two cases. Forensic Science International. 2001, 115: 135-141. 10.1016/S0379-0738(00)00322-4.CrossRefPubMed Verma SK, Dev G, Tyagi AK, Goomber S, Jain GV: Argemone mexicana poisoning: autopsy findings of two cases. Forensic Science International. 2001, 115: 135-141. 10.1016/S0379-0738(00)00322-4.CrossRefPubMed
26.
go back to reference Adjobimey T, Edayé I, Lagnika L, Gbenou J, Moudachirou M, Sanni A: Activités antiplasmodiales in vitro de quelques plantes antipaludiques de la pharmacopée béninoise. C R Chimie. 2004, 7: 1023-1027. 10.1016/j.crci.2003.10.022.CrossRef Adjobimey T, Edayé I, Lagnika L, Gbenou J, Moudachirou M, Sanni A: Activités antiplasmodiales in vitro de quelques plantes antipaludiques de la pharmacopée béninoise. C R Chimie. 2004, 7: 1023-1027. 10.1016/j.crci.2003.10.022.CrossRef
27.
go back to reference Guindo M: Contribution à l'étude du traitement traditionnel du "suma" (paludisme). 1988, Universite de Bamako, Ecole Nationale de Médecine et de Pharmacie du Mali Guindo M: Contribution à l'étude du traitement traditionnel du "suma" (paludisme). 1988, Universite de Bamako, Ecole Nationale de Médecine et de Pharmacie du Mali
28.
go back to reference Nadkarni AK: Dr K. M. Nadkarni's Indian Materia Medica. 1976, Bombay: Popular Prakashan, 3 Nadkarni AK: Dr K. M. Nadkarni's Indian Materia Medica. 1976, Bombay: Popular Prakashan, 3
29.
go back to reference Blair S, Correa A, Madrigal B, Zuluaga CB, Franco HD: Plantas antimalaricas. 1991, Medellin, Colombia: Editorial Universidad de Antioquia Blair S, Correa A, Madrigal B, Zuluaga CB, Franco HD: Plantas antimalaricas. 1991, Medellin, Colombia: Editorial Universidad de Antioquia
30.
go back to reference WHO: Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. 2003, Geneva: World Health Organisation WHO: Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. 2003, Geneva: World Health Organisation
31.
go back to reference Willcox M, Olanrewaju I: Guidelines for clinical studies on herbal antimalarials. Traditional Medicinal Plants and Malaria. Edited by: Willcox M, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press, Hardman R (Series Editor) Willcox M, Olanrewaju I: Guidelines for clinical studies on herbal antimalarials. Traditional Medicinal Plants and Malaria. Edited by: Willcox M, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press, Hardman R (Series Editor)
32.
go back to reference Willcox ML, Graz B, Falquet J, Sidibe O, Forster M, Diallo D: Argemone mexicana decoction for the treatment of uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg. 2007, 101: 1190-1198. 10.1016/j.trstmh.2007.05.017.CrossRefPubMed Willcox ML, Graz B, Falquet J, Sidibe O, Forster M, Diallo D: Argemone mexicana decoction for the treatment of uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg. 2007, 101: 1190-1198. 10.1016/j.trstmh.2007.05.017.CrossRefPubMed
33.
go back to reference Sidibe O: Etude d’Argemone mexicana Linn. dans le traitement traditionnel du paludisme non compliqué dans le village de Missidougou, région de Sikasso, Mali. 2006, University of Bamako, Faculté de Médecine, Pharmacologie et Odonto-Stomatologie Sidibe O: Etude d’Argemone mexicana Linn. dans le traitement traditionnel du paludisme non compliqué dans le village de Missidougou, région de Sikasso, Mali. 2006, University of Bamako, Faculté de Médecine, Pharmacologie et Odonto-Stomatologie
34.
go back to reference Guissou IP: Rapport d'Expertise Toxicologique: Evaluation de la Toxicite et du pouvoir irritant d'un decocte aqueux des feuilles d'Argemone mexicana (Papaveraceae). 2007, Ougadougou: Laboratoire de Biologie, Departement Medecine - Pharmacopee Traditionnelles, IRSS, Book Rapport d'Expertise Toxicologique: Evaluation de la Toxicite et du pouvoir irritant d'un decocte aqueux des feuilles d'Argemone mexicana (Papaveraceae) Guissou IP: Rapport d'Expertise Toxicologique: Evaluation de la Toxicite et du pouvoir irritant d'un decocte aqueux des feuilles d'Argemone mexicana (Papaveraceae). 2007, Ougadougou: Laboratoire de Biologie, Departement Medecine - Pharmacopee Traditionnelles, IRSS, Book Rapport d'Expertise Toxicologique: Evaluation de la Toxicite et du pouvoir irritant d'un decocte aqueux des feuilles d'Argemone mexicana (Papaveraceae)
35.
go back to reference Graz B, Willcox M, Diakite C, Falquet J, Dakouo F, Sidibe O, Giani S, Diallo D: Argemone mexicana decoction versus Artesunate / Amodiaquine for the home-based management of malaria in Mali. Policy and public health implications. Transactions of the Royal Society of Tropical Medicine & Hygiene. 2010, 104: 33-41. 10.1016/j.trstmh.2009.07.005.CrossRef Graz B, Willcox M, Diakite C, Falquet J, Dakouo F, Sidibe O, Giani S, Diallo D: Argemone mexicana decoction versus Artesunate / Amodiaquine for the home-based management of malaria in Mali. Policy and public health implications. Transactions of the Royal Society of Tropical Medicine & Hygiene. 2010, 104: 33-41. 10.1016/j.trstmh.2009.07.005.CrossRef
36.
go back to reference Sirima SB, Konate A, Tiono AB, Convelbo N, Cousens S, Pagnoni F: Early treatment of childhood fevers with pre-packaged antimalarial drugs in the home reduces severe malaria morbidity in Burkina Faso. Trop Med Int Health. 2003, 8: 133-139. 10.1046/j.1365-3156.2003.00997.x.CrossRefPubMed Sirima SB, Konate A, Tiono AB, Convelbo N, Cousens S, Pagnoni F: Early treatment of childhood fevers with pre-packaged antimalarial drugs in the home reduces severe malaria morbidity in Burkina Faso. Trop Med Int Health. 2003, 8: 133-139. 10.1046/j.1365-3156.2003.00997.x.CrossRefPubMed
37.
go back to reference Willcox ML, Graz B, Diakite C, Falquet J, Dackouo F, Sidibe O, Giani S, Diallo D: Is parasite clearance clinically important after malaria treatment in a high transmission area? A 3-month follow-up of home-based management with herbal medicine or ACT. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2011, 105: 23-31. 10.1016/j.trstmh.2010.10.003.CrossRefPubMed Willcox ML, Graz B, Diakite C, Falquet J, Dackouo F, Sidibe O, Giani S, Diallo D: Is parasite clearance clinically important after malaria treatment in a high transmission area? A 3-month follow-up of home-based management with herbal medicine or ACT. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2011, 105: 23-31. 10.1016/j.trstmh.2010.10.003.CrossRefPubMed
38.
go back to reference Verkman AS: Drug discovery in academia. American Journal of Physiology - Cell Physiology. 2004, 286: C465-474. 10.1152/ajpcell.00397.2003.CrossRefPubMed Verkman AS: Drug discovery in academia. American Journal of Physiology - Cell Physiology. 2004, 286: C465-474. 10.1152/ajpcell.00397.2003.CrossRefPubMed
39.
go back to reference Simoes-Pires CA: Investigation of antiplasmodial compounds from various plant extracts: Argemone mexicana L. (Papaveraceae), Licania octandra (Hoffmanns. ex. Roem & Schult) Kuntze (Chrysobalanaceae) and Syzygium cumini (L.) Skeels (Myrtaceae). 2009, Universite de Geneve, Section des Sciences Pharmaceutiques, Laboratoire de Pharmacognosie et Phytochimie Simoes-Pires CA: Investigation of antiplasmodial compounds from various plant extracts: Argemone mexicana L. (Papaveraceae), Licania octandra (Hoffmanns. ex. Roem & Schult) Kuntze (Chrysobalanaceae) and Syzygium cumini (L.) Skeels (Myrtaceae). 2009, Universite de Geneve, Section des Sciences Pharmaceutiques, Laboratoire de Pharmacognosie et Phytochimie
40.
go back to reference Pan G-Y, Wang G-J, Liu X-D, Fawcett JP, Xie Y-Y: The Involvement of P-Glycoprotein in Berberine Absorption. Pharmacology & Toxicology. 2002, 91: 193-197. 10.1034/j.1600-0773.2002.t01-1-910403.x.CrossRef Pan G-Y, Wang G-J, Liu X-D, Fawcett JP, Xie Y-Y: The Involvement of P-Glycoprotein in Berberine Absorption. Pharmacology & Toxicology. 2002, 91: 193-197. 10.1034/j.1600-0773.2002.t01-1-910403.x.CrossRef
41.
go back to reference Addae-Kyreme J: Cryptolepis sanguinolenta. Traditional Medicinal Plants and Malaria. Edited by: Willcox ML, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press Addae-Kyreme J: Cryptolepis sanguinolenta. Traditional Medicinal Plants and Malaria. Edited by: Willcox ML, Bodeker G, Rasoanaivo P. 2004, Boca Raton: CRC Press
43.
go back to reference WHO: Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated Falciparum Malaria in Areas with intense Transmission. WHO/MAL/96.1077. 1996, Geneva: World Health Organisation WHO: Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated Falciparum Malaria in Areas with intense Transmission. WHO/MAL/96.1077. 1996, Geneva: World Health Organisation
Metadata
Title
A “reverse pharmacology” approach for developing an anti-malarial phytomedicine
Authors
Merlin L Willcox
Bertrand Graz
Jacques Falquet
Chiaka Diakite
Sergio Giani
Drissa Diallo
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Malaria Journal / Issue Special Issue 1/2011
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-10-S1-S8

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