罗格列酮
过氧化物酶体增殖物激活受体
PPAR激动剂
化学
药理学
配体结合分析
超滤(肾)
受体
兴奋剂
交易激励
生物化学
生物
转录因子
基因
作者
Yong-Soo Choi,Yujung Jung,Su‐Nam Kim
出处
期刊:Molecules
[Multidisciplinary Digital Publishing Institute]
日期:2015-07-28
卷期号:20 (8): 13753-13763
被引量:30
标识
DOI:10.3390/molecules200813753
摘要
Peroxisome proliferator-activated receptors (PPARs) are key nuclear receptors and therapeutic targets for the treatment of metabolic diseases through the regulation of insulin resistance, diabetes, and dyslipidemia. Although a few drugs that target PPARs have been approved, more diverse and novel PPAR ligands are necessary to improve the safety and efficacy of available drugs. To expedite the search for new natural agonists of PPARs, we developed a screening assay based on ultrafiltration liquid chromatography-mass spectrometry (LC-MS) that is compatible with complex samples such as dietary foods or botanical extracts. The known PPARα and/or PPARγ ligands resveratrol and rosiglitazone were used as positive controls to validate the developed method. When applied to the screening of an Artemisia argyi extract, eupatilin was identified as a selective PPARα ligand. A PPAR competitive binding assay based on FRET detection also confirmed eupatilin as a selective PPARα agonist exhibiting a binding affinity of 1.18 μM (IC50). Furthermore, eupatilin activation of the transcriptional activity of PPARα was confirmed using a cell-based transactivation assay. Thus, ultrafiltration LC-MS is a suitable assay for the identification of PPAR ligands in complex matrixes such as extracts of dietary foods and botanicals.
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