Identification of Plant Phenolics from <i>Paulownia tomentosa</i> and <i>Morus alba</i> as Novel PPARγ Partial Agonists and Hypoglycemic Agents

The aim of our study was to determine the PPARγ agonism and hypoglycemic activity of natural phenolics isolated from <i>Paulownia tomentosa</i> and <i>Morus alba</i>. We started with a molecular docking preselection, followed by <i>in vitro</i> cell culture assays, such as PPARγ luciferase reporter gene assay and PPARγ protein expression by Western blot analysis. The ability of the selected compounds to induce GLUT4 translocation in cell culture and lower blood glucose levels in chicken embryos was also determined. Among the thirty-six plant phenolic compounds, moracin M showed the highest hypoglycemic effect in an <i>in ovo</i> experiment (7.33 ± 2.37%), followed by mulberrofuran Y (3.84 ± 1.34%) and diplacone (3.69 ± 1.37%). Neither moracin M nor mulberrofuran Y showed a clear effect on the enhancement of GLUT4 translocation or agonism on PPARγ, while diplacone succeeded in both (3.62 ± 0.16% and 2.4-fold ± 0.2, respectively). Thus, we believe that the compounds moracin M, mulberrofuran Y, and diplacone are suitable for further experiments to elucidate their mechanisms of action.