Screening of saponins and sapogenins from Medicago species as potential PPAR? agonists and X-ray structure of the complex PPAR?/caulophyllogenin.

ABSTRACT: A series of saponins and sapogenins from Medicago species were tested for their ability to bind and activate the nuclear receptor PPAR? by SPR experiments and transactivation assay, respectively. The SPR analysis proved to be a very powerful and fast technique for screening a large number of compounds for their affinity to PPAR? and selecting the better candidates for further studies. Based on the obtained results, the sapogenin caulophyllogenin was proved to be a partial agonist towards PPAR? and the X-ray structure of its complex with PPAR? was also solved, in order to investigate the binding mode in the ligand binding domain of the nuclear receptor. This is the first known crystal structure of a sapogenin directly interacting with PPAR?. Another compound of the series, the echinocistic acid, showed antagonist activity towards PPAR?, a property that could be useful to inhibit the adipocyte differentiation which is a typical adverse effect of PPAR? agonists. This study confirms the interest on saponins and sapogenins as a valuable natural resource exploitable in the medical and food industry for ameliorating the metabolic syndrome.

SUBMITTER: Montanari R 

PROVIDER: S-EPMC4901321 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature