Quantitative Bioactivity Signatures of Dietary Supplements and Natural Products

Dietary supplements and natural products are often marketed
as
safe and effective alternatives to conventional drugs, but their safety
and efficacy are not well regulated. To address the lack of scientific
data in these areas, we assembled a collection of Dietary Supplements
and Natural Products (DSNP), as well as Traditional Chinese Medicinal
(TCM) plant extracts. These collections were then profiled in a series
of in vitro high-throughput screening assays, including
a liver cytochrome p450 enzyme panel, CAR/PXR signaling pathways,
and P-glycoprotein (P-gp) transporter assay activities. 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 (the NCATS Pharmaceutical Collection or NPC).
Many of the approved drugs have well-annotated mechanisms of action
(MOAs), 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 NPC to predict the
MOAs of the DSNP/TCM substances. Our results suggest that many of
these substances may have significant bioactivity and potential toxicity,
and they provide a starting point for further research on their clinical
relevance.