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.

中文翻译：

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膳食补充剂和天然产品的定量生物活性特征

膳食补充剂和天然产品对其安全性和有效性的监督很少。我们收集了一系列膳食补充剂和天然产品 (DSNP) 以及中药 (TCM) 植物提取物，这些提取物经过体外筛选一组测定，包括肝细胞色素 p450 酶组、CAR/PXR 信号通路和 P-gp 转运蛋白测定，以评估它们的活性。该管道通过显着的代谢途径促进了对天然产物-药物相互作用 (NaPDI) 的研究。此外，我们将 DSNP/TCM 物质的活性概况与批准的药物集合的活性概况进行了比较。许多已获批准的药物具有详细注释的作用机制 (MOA)，而大多数 DSNP 和 TCM 样本的 MOA 仍然未知。基于具有相似活性谱的化合物倾向于共享相似的目标或 MOA 的前提，我们对库活性谱进行聚类以识别与 NCATS 药物集合的重叠，以预测 DSNP/TCM 物质的 MOA。全面的，我们强调了四个重要的生物活性特征（通过 p 值测量）作为该预测的示例。这些结果可以作为进一步探索这些物质的毒性潜力和临床相关性的起点。