title: Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification.
abstract: There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard. The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly-pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect. This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers. While preserving biodiversity, this will serve as a primary step towards the development of standardized phytomedicines, as well as facilitate lead discovery for chemical prioritization and downstream clinical development.
authors.affiliation: Centre for Research on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies (IMPM), P. O. Box 8013, Yaoundé, Cameroon ; Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, University of Ghana, P. O. Box LG 581, Legon, Accra Ghana.
authors.forename: Protus Arrey
authors.initials: PA
authors.lastname: Tarkang
authors.affiliation: Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, University of Ghana, P. O. Box LG 581, Legon, Accra Ghana.
authors.forename: Regina
authors.initials: R
authors.lastname: Appiah-Opong
authors.affiliation: Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, P. O. Box LG581, Legon, Accra Ghana.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ofori
authors.affiliation: Malaria Research Laboratory, Centre Pasteur Cameroon, BP 1274 Yaoundé, Cameroon.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Ayong
authors.affiliation: Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, University of Ghana, P. O. Box LG 581, Legon, Accra Ghana ; School of Pharmacy, University of Ghana, P.O. Box LG43, Legon, Accra Ghana.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Nyarko
keywords: HPLC-based anti-malarial profiling; High throughput screening (HTS); In vivo pharmacology; Malaria; Multi-target effects; Pharmacokinetics; Phytotherapy; Reverse pharmacology