Annam Suresh Chandra V A R, Neal William M, Pandey Pankaj, Avula Bharathi, Katragunta Kumar, Husain Islam, Khan Shabana I, Koturbash Igor, Gurley Bill J, Khan Ikhlas A, Chittiboyina Amar G
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, United States.
Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, United States.
ACS Omega. 2024 Dec 16;9(52):51394-51407. doi: 10.1021/acsomega.4c08293. eCollection 2024 Dec 31.
Despite promising preliminary biology, natural products isolation efforts may be confounded when the active compound is not isolated during bioassay-guided purification or classical pharmacognostic research investigations. A more rational isolation procedure connecting the polypharmacology of an herb to its individual constituents must be applied to better detect bioactive molecules before tedious analytical steps are considered. While (yohimbe) has been traditionally used in herbal medicine as a general tonic, an aphrodisiac, a performance enhancer, and an integral part of various dietary supplements, the hydroethanolic extract of yohimbe was identified to possess at least 3-4-fold induction of the pregnane X receptor (PXR) at 30 μg/mL, a key nuclear receptor implicated in adverse interactions, ., herb-drug interactions (HDIs). For rapid dereplication of potential HDI agents within yohimbe, a novel MS/MS-based molecular networking analysis was integrated with data and analysis of activity at PXR. Analysis of the molecular network of biologically active fractions resulted in the dereplication of three oxindole alkaloids, 14 indole alkaloids, and eight -oxide alkaloids as the primary causative agents for PXR induction. The findings of this study indicate that this strategy could effectively guide the rapid dereplication of bioactive causative agents within complex botanical extracts. Additionally, it serves as a proof-of-concept for using integrated MS/MS-based molecular networking analysis to assess the safety profile of botanical supplements.
尽管初步生物学研究前景乐观，但在生物测定指导的纯化过程或传统生药学研究调查中，如果未分离出活性化合物，天然产物的分离工作可能会受到干扰。在考虑繁琐的分析步骤之前，必须应用一种更合理的分离程序，将草药的多药理学与其单个成分联系起来，以便更好地检测生物活性分子。虽然育亨宾传统上在草药中用作一般滋补品、壮阳药、性能增强剂以及各种膳食补充剂的组成部分，但育亨宾的水乙醇提取物在30μg/mL时被确定对孕烷X受体（PXR）有至少3至4倍的诱导作用，PXR是一种与不良相互作用（即草药-药物相互作用，HDIs）有关的关键核受体。为了快速排除育亨宾中潜在的HDI剂，将基于MS/MS的新型分子网络分析与PXR活性数据和分析相结合。对生物活性部分的分子网络分析导致排除了三种氧化吲哚生物碱、十四种吲哚生物碱和八种氧化生物碱是诱导PXR的主要致病因子。本研究结果表明，该策略可以有效地指导复杂植物提取物中生物活性致病因子的快速排除。此外，它为使用基于MS/MS的综合分子网络分析来评估植物性补充剂的安全性提供了概念验证。
