Abstract
Translation of traditional medicine is moving away from the reductionist approach towards harnessing the synergy of poly-pharmacological phyto-combinations that modulate the activity of target networks of underlying disease phenotypes. Metabolomics enabled the profiling of herbal extracts and formulations in high resolution through LC-MS/MS, GC-MS and NMR providing the possibility of multi-component drug discovery. Phytopharmaceuticals are multi-molecular combinations which follow a combinatory treatment module which minimizes off-target toxicity by synergistic potency and improve outcomes by synergistic efficacy. Combination synergy is a multi-dimensional concept where synergy can be observed from a network pharmacology perspective. Network pharmacology uses systems-level drug–response phenotypes originating from various ‘omics’ platforms. This network pharmacology with metabolomics has been proven to be effective in elucidating the mechanisms of action of medicinal plants and complex traditional formulations. LC-MS/MS of medicinal plants along with network pharmacology unveil synergistic molecular combinations which interact with neighbouring targets in a combination synergy network. Case studies on some traditional herbs mentioned in Ayurveda, has been reported based on the combination of network-based methods and metabolomics for establishing the mechanism for their therapeutic potentials. The synergistic combination of molecules interacts with target-disease networks which provide novel, mechanistic insights towards understanding their therapeutic potentials. This review along with case-studies illustrates various strategies to explore the mechanism of action for different synergistic natural products combinations through neighbourhood-based network pharmacology approach.
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