Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification

• Published in: Biomarker research 2016-12, Vol.4 (1), p.25, Article 25
• Main Authors: Tarkang, Protus Arrey, Appiah-Opong, Regina, Ofori, Michael F, Ayong, Lawrence S, Nyarko, Alexander K
• Format: Article
• Language: English
• Subjects: Biomolecules; Botanical research; Care and treatment; Identification and classification; Malaria; Phytochemistry; Review
• ISSN: 2050-7771; 2050-7771
• DOI: 10.1186/s40364-016-0077-0

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.