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.
Highlights
Malaria control initiatives have led to substantial improvement in the number of saved lives in vulnerable populations, in those with access to effective anti-malarial drugs [1]
A dependable alternative is a combination of various solvents, such as a multi-phase solvent system composed of a mixture of solvents, such as chloroform-methanol—water, which has been proposed for such studies which are performed with pure methanol or a mixture containing it [31]
An aspect that needs to be considered is that lipophilic compounds do not elute from C18 reversed phase columns and certain methanol—water mixtures do not extract chlorophyll from plant aerial parts, which might be an advantage for incorporating LC analysis in mass spectrometry (MS)— based metabolomics [13]
Summary
Malaria control initiatives have led to substantial improvement in the number of saved lives in vulnerable populations, in those with access to effective anti-malarial drugs [1]. Malaria parasite has developed resistance to many of the currently available drugs, including emerging resistance to the core artemisinin component of the artemisinin-based combination (ACT) therapies [6]. This underscores the need to explore new therapeutic strategies from natural products. The physiopathology of malaria is not fully understood, the knowledge that its pathogenesis involves multiple factors, obliges effective therapeutic approaches to shift from the conventional “one target, one drug” to a new “multi-target, multidrug” model [7, 8]. The requirements for the development of new anti-malarials to support the current therapeutic and eradication agenda include novel modes of action with no cross resistance to current drugs, multiple-stage efficacy and anti-relapsing activity [9]
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