Peroxisome proliferator-activated receptors (PPARs) belong to the superfamily of nuclear receptors and represent the targets for the therapeutical treatment of type 2 diabetes, dyslipidemia and hyperglycemia associated with metabolic syndrome. Some medicinal plants have been traditionally used to treat this kind of metabolic diseases. Today only few drugs targeting PPARs have been approved and for this reason, the rapid identification of novel ligands and/or chemical scaffolds starting from natural extracts would benefit of a selective affinity ligand fishing assay. In this paper we describe the development of a new ligand fishing assay based on size exclusion chromatography (SEC) coupled to LC-MS for the analysis of complex samples such as botanical extracts. The known PPARα and PPARγ ligands, WY-14643 and rosiglitazone respectively, were used for system development and evaluation. The system has found application on an methanolic extract, containing saponins, a class of chemical compounds which have attracted interest as PPARs ligands because of their hypolipidemic and insulin-like properties. A new SEC-AS-MS method has been developed for the affinity screening of PPARα and PPARγ ligands. The system proved to be highly specific and will be used to improve the throughput for the identification of new selective metabolites from natural souces targeting PPARα and PPARγ.

中文翻译：

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开发用于通过 SEC-MS 对 PPARα 和 PPARγ 受体进行天然提取物亲和力筛选的分析平台


过氧化物酶体增殖物激活受体 (PPAR) 属于核受体超家族，是治疗 2 型糖尿病、血脂异常和与代谢综合征相关的高血糖的靶标。一些药用植物传统上被用来治疗此类代谢性疾病。目前，只有少数针对 PPAR 的药物已获得批准，因此，从天然提取物中快速鉴定新型配体和/或化学支架将受益于选择性亲和配体捕捞测定。在本文中，我们描述了一种基于尺寸排阻色谱 (SEC) 与 LC-MS 联用的新型配体捕捞测定的开发，用于分析植物提取物等复杂样品。已知的 PPARα 和 PPARγ 配体分别为 WY-14643 和罗格列酮，用于系统开发和评估。该系统已应用于含有皂苷的甲醇提取物，皂苷是一类化合物，由于其降血脂和胰岛素样特性而作为 PPAR 配体引起了人们的兴趣。开发了一种新的 SEC-AS-MS 方法用于 PPARα 和 PPARγ 配体的亲和力筛选。该系统被证明具有高度特异性，将用于提高从天然来源中鉴定针对 PPARα 和 PPARγ 的新选择性代谢物的通量。