Plant omics is an emerging field of systems science and offers the prospects of evidence-based evaluation of traditional herbal medicines in human diseases. To this end, the powdered root of Yashtimadhu (Glycyrrhiza glabra L.), commonly known as liquorice, is frequently used in Indian Ayurvedic medicine with an eye to neuroprotection but its target proteins, mechanisms of action, and metabolites remain to be determined. Using a metabolomics and network pharmacology approach, we identified 98,097 spectra from positive and negative polarities that matched to ∼1600 known metabolites. These metabolites belong to terpenoids, alkaloids, and flavonoids, including both novel and previously reported active metabolites such as glycyrrhizin, glabridin, liquiritin, and other terpenoid saponins. Novel metabolites were also identified such as quercetin glucosides, coumarin derivatives, beta-carotene, and asiatic acid, which were previously not reported in relation to liquorice. Metabolite–protein interaction-based network pharmacology analyses enriched 107 human proteins, which included dopamine, serotonin, and acetylcholine neurotransmitter receptors among other regulatory proteins. Pathway analysis highlighted the regulation of signaling kinases, growth factor receptors, cell cycle, and inflammatory pathways. In vitro validation confirmed the regulation of cell cycle, MAPK1/3, PI3K/AKT pathways by liquorice. The present data-driven, metabolomics and network pharmacology study paves the way for further translational clinical research on neuropharmacology of liquorice and other traditional medicines.

中文翻译：

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植物组学：甘草的代谢组学和网络药理学，印度阿育吠陀医学 Yashtimadhu

植物组学是系统科学的一个新兴领域，为人类疾病中传统草药的循证评估提供了前景。为此，Yashtimadhu ( Glycyrrhiza glabraL.)，通常称为甘草，经常用于印度阿育吠陀医学，着眼于神经保护作用，但其靶蛋白、作用机制和代谢物仍有待确定。使用代谢组学和网络药理学方法，我们从正极性和负极性中鉴定了 98,097 个光谱，这些光谱与 1600 种已知代谢物相匹配。这些代谢物属于萜类、生物碱和黄酮类化合物，包括新的和以前报道的活性代谢物，如甘草甜素、光甘草定、甘草苷和其他萜类皂苷。还鉴定了新的代谢物，例如槲皮素糖苷、香豆素衍生物、β-胡萝卜素和积雪草酸，这些以前没有与甘草有关。基于代谢物-蛋白质相互作用的网络药理学分析丰富了 107 种人类蛋白质，其中包括多巴胺、血清素和乙酰胆碱神经递质受体以及其他调节蛋白。通路分析强调了信号激酶、生长因子受体、细胞周期和炎症通路的调节。体外验证证实了甘草对细胞周期、MAPK1/3、PI3K/AKT 通路的调节。目前的数据驱动、代谢组学和网络药理学研究为甘草和其他传统药物神经药理学的进一步转化临床研究铺平了道路。