Books and Book Chapters

      Systems pharmacology investigation of mechanism of action of nutraceuticals

      Messinis, D. E.; Latino, D. A. R. S.; Pospisil, P.; Poussin, C.; Peitsch, M. C.; Hoeng, J.

      Date published
      Jan 29, 2021
      DOI
      10.1016/B978-0-12-821038-3.00024-0
      ISBN
      9780128212462
      Published in
      Nutraceuticals: Efficacy, Safety and Toxicity, Second Edition
      Editors
      Gupta, R. C.; Lall, R.; Srivastava, A.
      Link to publication
      Topic
      Summary

      Nutraceuticals’ properties render them a good source of potential drug leads in pharmaceutical research, but the elucidation of their mechanism of action (MoA) is challenging, partly because natural compounds can bind multiple targets with unrelated structures. In this work, we present a pipeline that integrates complementary systems biology and chemoinformatics-based approaches with the goal of identifying potential targets and generating MoA hypotheses that can be tested in a new cycle of experiments. We focus on how we can integrate knowledge from multiple sources into an ensemble score and translate our results into biological insights, providing use cases on three extensively studied nutraceuticals, epigallocatechin-3-gallate, quercetin, and resveratrol as well as on a prototypical proinflammatory stimulus, TNF-α. Fifty-seven of our top 60 predicted targets were already identified in the literature as experimentally perturbed by the corresponding compounds, interestingly observing anticancer, antiviral, and antibacterial MoA to be shared among the tested nutraceuticals.

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