Takeda G Protein-Coupled Receptor 5 and Peroxisome Proliferator-Activated Receptor-Gamma Activation by Pinocembrin and Pinostrobin Isolated from Lindera sericea

<i>Lindera sericea</i> var. <i>sericea</i> (Japanese common name: "Kekuromoji") is a deciduous shrub belonging to the Lauraceae family. Mainly distributed in Japan and Korea, <i>L. sericea</i> has been traditionally used as a source of essential oils and has not been characterized as a medicinal plant. In this study, we aimed to isolate and identify compounds that activate Takeda G protein-coupled receptor 5 (TGR5) and peroxisome proliferator-activated receptor-γ (PPARγ). Bioactivities were evaluated using a dual-color real-time bioluminescence monitoring system. The methanolic extract of <i>L. sericea</i> showed significant dose-dependent TGR5 activation and modest PPARγ activation. Spectroscopic analysis identified <i>rac</i>-pinocembrin (<i>rac</i>-<b>1</b>) and <i>rac</i>-pinostrobin (<i>rac</i>-<b>2</b>) as the major bioactive compounds in the methanolic extract. Reporter assays revealed that <i>rac</i>-<b>2</b> is a TGR5 activator, whereas both <i>rac</i>-<b>1</b> and <i>rac</i>-<b>2</b> are modest PPARγ activators. We then separated the enantiomers of pinocembrin (<b>1</b>) and pinostrobin (<b>2</b>) using chiral column chromatography. Both enantiomers of <b>2</b> contributed comparably to TGR5 activation, whereas each pair of enantiomers (<b>1</b> and <b>2</b>) exhibited similar activity within the same compound toward PPARγ. These findings suggest that <i>L. sericea</i> is a promising source of bioactive compounds with potential metabolic regulatory activity.