TY - JOUR
T1 - Application of multi-target phytotherapeutic concept in malaria drug discovery
T2 - A systems biology approach in biomarker identification
AU - Tarkang, Protus Arrey
AU - Appiah-Opong, Regina
AU - Ofori, Michael F.
AU - Ayong, Lawrence S.
AU - Nyarko, Alexander K.
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/12/13
Y1 - 2016/12/13
N2 - 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.
AB - 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.
KW - HPLC-based anti-malarial profiling
KW - High throughput screening (HTS)
KW - In vivo pharmacology
KW - Malaria
KW - Multi-target effects
KW - Pharmacokinetics
KW - Phytotherapy
KW - Reverse pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85015734511&partnerID=8YFLogxK
U2 - 10.1186/s40364-016-0077-0
DO - 10.1186/s40364-016-0077-0
M3 - Review article
AN - SCOPUS:85015734511
SN - 2050-7771
VL - 4
JO - Biomarker Research
JF - Biomarker Research
IS - 1
M1 - 25
ER -