Osthole Activates FGF21 Expression by Mediating Activation of ATF4 in Human Hepatocyte HepG2 Cells
Osthole is a natural coumarin derivative found in several medicinal plants, including <i>Cnidium monnieri</i> and <i>Angelica pubescens</i>. 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 (<i>FGF21</i>) expression. Among the known transcription factors that regulate FGF21 induction, activating transcription factor 4 (<i>ATF4</i>) 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 <i>FGF21</i> expression. These findings suggest that osthole activates <i>FGF21</i> expression via ATF4 activation.
Authors
- Itsuki Terao (ORCID: https://orcid.org/0000-0003-0662-5637)
- Masaya Araki
- Hitoshi Shimano (ORCID: https://orcid.org/0000-0002-5562-5572)
- Takashi Matsuzaka (ORCID: https://orcid.org/0000-0002-5898-3463)
- Yoshimi Nakagawa (ORCID: https://orcid.org/0000-0001-8710-5232)
- Yuhei Tsuchimoto
- Hirohito Sone
- Tomoya Yamashita
- Kyohei Suzuki
- Ryo Kanazawa
- Akishi Taguchi
Institutions
- University of Tsukuba (JP)
- Tokyo Medical University Ibaraki Medical Center (JP)
- University of Toyama (JP)
- Niigata University (JP)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2026-01-19
- DOI
- https://doi.org/10.3390/ijms27021003
- Primary Topic
- Plant chemical constituents analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Institute of Natural Medicine, University of Toyama
- Japan Society for the Promotion of Science