The selection of medicinal plants’ chemical markers focuses on bioactivity as the primary goal, followed by the nature of secondary metabolites, their stability, and availability. However, herbal medicines are valued for their complex and holistic pharmacological effects. A correct chemical marker can be carefully selected by a systematic clarification of their chemical-biological relationships. In the current study, the multi-informative molecular networking (MIMN) approach was employed to construct the anti-inflammatory metabolomic pattern of a heat-clearing herb, Scrophularia ningpoensis Hemsl. (S. ningpoensis). The MIMN molecular families characterized by cinnamic acid glycosides showed a higher bioactivity score compared with the other two major chemical classes (iridoid glycosides and iridoid-cinnamic acid glycosides). The Global Natural Product Social Molecular Networking (GNPS) and Reaxys database were used to assist in the putative annotation of eighteen metabolites from the bioactive and non-bioactive molecular families. The anti-inflammatory validation step was based on the detection of reactive oxygen species (ROS) generation by activated human neutrophils. All compounds from the bioactive MIMN molecular families dose-dependently inhibited the total ROS generation promoted by fMLF (IC50: 0.04–0.42 μM), while the compounds from non-bioactive MIMN clusters did not show any significant anti-inflammatory effect. The ROS-dependent anti-inflammatory activity of these cinnamic acid glycosides was attributed to their oxygen radical scavenging ability. The most abundant cinnamic acid glycoside, angoroside C (IC50: 0.34 μM) was suggested to be selected as a chemical marker for S. ningpoensis. In this study, the MIMN platform was applied to assist in the chemical marker selection of S. ningpoensis. The correct selection of markers will aid in the compilation and revision of herbal monographs and pharmacopeias resulting in the precise analysis and classification of medicinal plants on a scientific basis.

中文翻译：

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化学计量学指导的化学标记选择：以清热草药宁波玄参为例

药用植物化学标记物的选择以生物活性为首要目标，其次是次级代谢产物的性质、稳定性和有效性。然而，草药因其复杂而全面的药理作用而受到重视。可以通过系统地阐明它们的化学-生物学关系来仔细选择正确的化学标记。在目前的研究中，采用多信息分子网络 (MIMN) 方法构建清热草药的抗炎代谢组学模式，玄参Hemsl。(宁波沙棘). 与其他两个主要化学类别（环烯醚萜苷和环烯醚萜-肉桂酸苷）相比，以肉桂酸苷为特征的 MIMN 分子家族显示出更高的生物活性评分。全球天然产物社会分子网络 (GNPS) 和 Reaxys 数据库用于协助对来自生物活性和非生物活性分子家族的 18 种代谢物进行推定注释。抗炎验证步骤基于检测活化的人嗜中性粒细胞产生的活性氧 (ROS)。来自生物活性 MIMN 分子家族的所有化合物剂量依赖性地抑制 fMLF 促进的总 ROS 生成（IC50: 0.04–0.42 μM)，而来自非生物活性 MIMN 簇的化合物没有显示出任何显着的抗炎作用。这些肉桂酸苷的 ROS 依赖性抗炎活性归因于它们的氧自由基清除能力。最丰富的肉桂酸苷，angoroside C (IC50: 0.34 μM)被建议作为化学标记宁波沙棘. 在本研究中，应用 MIMN 平台辅助化学标记选择宁波沙棘. 正确选择标记将有助于草药专着和药典的编写和修订，从而在科学的基础上对药用植物进行精确的分析和分类。