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

## TL;DR

This study identifies compounds in Lindera sericea that activate receptors involved in metabolism, suggesting potential medicinal use.

## Contribution

The study isolates and characterizes pinocembrin and pinostrobin enantiomers from Lindera sericea as activators of TGR5 and PPARγ.

## Key findings

- Methanolic extract of Lindera sericea activates TGR5 and PPARγ receptors.
- Pinocembrin and pinostrobin enantiomers show comparable TGR5 and PPARγ activation.
- Lindera sericea is a promising source of bioactive compounds with metabolic regulatory potential.

## Abstract

Lindera sericea var. sericea (Japanese common name: “Kekuromoji”) is a deciduous shrub belonging to the Lauraceae family. Mainly distributed in Japan and Korea, L. sericea 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 L. sericea showed significant dose-dependent TGR5 activation and modest PPARγ activation. Spectroscopic analysis identified rac-pinocembrin (rac-1) and rac-pinostrobin (rac-2) as the major bioactive compounds in the methanolic extract. Reporter assays revealed that rac-2 is a TGR5 activator, whereas both rac-1 and rac-2 are modest PPARγ activators. We then separated the enantiomers of pinocembrin (1) and pinostrobin (2) using chiral column chromatography. Both enantiomers of 2 contributed comparably to TGR5 activation, whereas each pair of enantiomers (1 and 2) exhibited similar activity within the same compound toward PPARγ. These findings suggest that L. sericea is a promising source of bioactive compounds with potential metabolic regulatory activity.