Quantitative bioactivity signatures of dietary supplements and natural products

Abstract

Dietary Supplements and Natural Products have minor oversight of their safety and efficacy. We assembled a collection of Dietary Supplements and Natural Products (DSNP) as well as Traditional Chinese Medicinal (TCM) Plant extracts, which were screened against an in vitro panel of assays, including a liver cytochrome p450 enzyme panel, CAR/PXR signaling pathways, and P-gp transporter assays, to assess their activity. This pipeline facilitated the interrogation of Natural Product-Drug Interaction (NaPDI) through prominent metabolizing pathways. In addition, we compared the activity profiles of the DSNP/TCM substances with those of an approved drug collection. Many of the approved drugs have well-annotated mechanisms of action (MOA) while the MOAs for most of the DSNP and TCM samples remain unknown. Based on the premise that compounds with similar activity profiles tend to share similar targets or MOA, we clustered the library activity profiles to identify overlap with the NCATS Pharmaceutical Collection to predict the MOAs of the DSNP/TCM substances. Overall, we highlight four significant bioactivity profiles (measured by p-values) as examples of this prediction. These results can be used as a starting point for further exploration on the toxicity potential and clinical relevance of these substances.