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

Protus Arrey Tarkang, Regina Appiah-Opong, Michael F. Ofori, Lawrence S. Ayong, Alexander K. Nyarko

Research output: Contribution to journalReview articlepeer-review

24 Citations (Scopus)

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.

Original languageEnglish
Article number25
JournalBiomarker Research
Volume4
Issue number1
DOIs
Publication statusPublished - 13 Dec 2016
Externally publishedYes

Keywords

  • HPLC-based anti-malarial profiling
  • High throughput screening (HTS)
  • In vivo pharmacology
  • Malaria
  • Multi-target effects
  • Pharmacokinetics
  • Phytotherapy
  • Reverse pharmacology

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