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Innovative Approaches for Establishing Biological Signatures of Natural Products

Introduction and Explanation of Need

Natural products, whether as herbal supplements or as part of a diet, are frequently consumed as a complex mixture. This complexity is further amplified by potential interactions with endogenous metabolic pathways, including those associated with the microbiome. The result is a collection of natural products and their metabolites that, individually and/or collectively, are associated with a network of biological activity. Importantly, in addition to direct action on biological targets, the activity of natural products can be influenced by an individual’s health and metagenomic background. The purpose of this research priority therefore is to advance the characterization and categorization of the biologic activity of complex natural products broadly, with an emphasis on determining metabolomic profiles.

Many of the techniques for studying complex mixtures of natural products have remained largely unchanged for many years and have not taken full advantage of innovative advances in biological and chemical methodologies and technologies. Understanding biological signatures of complex natural products requires innovative approaches and tools beyond those traditionally used for analyzing a single molecule against a single mechanistic target. To move the field forward, there must be a renewed emphasis on multidisciplinary high-impact approaches to overcome conceptual, methodological, and technological hurdles that hinder advances in natural products research.

One promising method is the incorporation of network pharmacology, an innovative approach that seeks to define the web of biologic targets for bioactive substances. This tool will facilitate the characterization and categorization of complex natural products. Information gleaned from network pharmacologic analyses may help predict pharmacological and biological mechanisms of action, including their influence on the microbiome.

What Does Success Look Like?

Researchers who are at the leading edge of science successfully incorporate novel natural products technologies in their research activities. In addition, these new technologies help elucidate pharmacological and metabolomic signatures that may provide a basis for understanding natural products’ biological activities.


  • Establish a state-of-the-art data repository of the chemical and biological signatures of natural products as a resource to aid researchers.
  • Develop new and innovative technologies to better understand the effects of natural products on the human biome.
  • Develop innovative bioinformatic technologies to better predict potential toxicities of dietary supplements, including botanical dietary supplements and pre-/probiotics.
  • Identify and develop novel bioassays to evaluate natural products and their analogs for their complementary effects in alleviating pain, symptoms of depression, or signs of anxiety.

Areas of Low Programmatic Priority

  • Research focused on a single compound or well-characterized mechanistic target.
  • Screening of natural product libraries in subcellular assays.
  • Bioactivity-guided fractionation projects.

Top Scientific Priorities