# Osthole Activates FGF21 Expression by Mediating Activation of ATF4 in Human Hepatocyte HepG2 Cells

## TL;DR

Osthole, a natural compound, activates FGF21 expression in liver cells by boosting ATF4 activity.

## Contribution

This study identifies ATF4 as a key mediator through which osthole activates FGF21 expression in HepG2 cells.

## Key findings

- Osthole increases FGF21 expression in HepG2 cells.
- ATF4 is upregulated by osthole and mediates FGF21 induction.
- ATF4 knockdown reduces osthole-induced FGF21 expression.

## Abstract

Osthole is a natural coumarin derivative found in several medicinal plants, including Cnidium monnieri and Angelica pubescens. It has been studied for its various biological properties, such as anti-inflammatory, neuroprotective, osteogenic, cardioprotective, antimicrobial, and antiparasitic effects. Osthole was found to induce Fibroblast growth factor 21 (FGF21) expression. Among the known transcription factors that regulate FGF21 induction, activating transcription factor 4 (ATF4) expression was found to be upregulated by osthole. Additionally, as osthole induced ATF4 downstream gene expression, it was concluded that it activates ATF4 signaling. ATF4 knockdown significantly suppressed osthole-mediated induction of FGF21 expression. These findings suggest that osthole activates FGF21 expression via ATF4 activation.