[Development of a cell-based peroxisome proliferator-activated receptors (PPARs) screening model and its application...

Peroxisome proliferators activated receptors (PPARs) are closely related to human chronic disease, such as diabetes mellitus and the other metabolic diseases. In this study, a cell-based PPARs (PPAR α/β/γ) model was developed for the screening of PPARs agonists from Alismatis Rhizoma (AR). Firstly, 293T cells were transfected with the reconstructed plasmid pBind-PPAR (α, β, or γ)-LBD and reporter gene pGL4.35, and the known PPARs agonists were used as the positive control (fenofibrate for PPARα, L165041 for PPARβ, and rosiglitazone for PPARγ). The ability of activation for PPARs was evaluated by analyzing the expression value of luciferase. Afterward, the 14 pure triterpenoids isolate from AR were analyzed on the developed PPARα, PPARβ and PPARγ screening assay method. The results showed that the compounds 5, 6, 7, 8, 13 and 14 from AR have the ability of activation for PPARα. The compounds 5 and 7 from AR have the ability of activation for PPARβ. The compounds 6, 7, 8 and 12 from RA have the ability of activation for PPARγ.In this study, the compound 12 from AR were found to display significant activation on PPARγ for the first time. AR triterpenoids extracts had the ability of activation for PPARα, PPARβ and PPARγ. The results suggested that triterpenoids extracts from AR were PPARα, PPARβ and PPARγ agonists. The results will help to provide reference for clinical application of AR, and establish a model for PPARs on 293T cell, which can be used to screen and evaluate PPARs natural agonists.