Wogonin, a Compound in <i>Scutellaria baicalensis</i>, Activates ATF4–FGF21 Signaling in Mouse Hepatocyte AML12 Cells

Yasunari Yamada; Hodaka Saito; Masaya Araki; Yuhei Tsuchimoto; Shin-ichi Muroi; Kyohei Suzuki; Kazufumi Toume; Jun-Dal Kim; Takashi Matsuzaka; Hirohito Sone; Hitoshi Shimano; Yoshimi Nakagawa

doi:10.3390/nu14193920

Nutrients (Sep 2022)

Wogonin, a Compound in <i>Scutellaria baicalensis</i>, Activates ATF4–FGF21 Signaling in Mouse Hepatocyte AML12 Cells

Yasunari Yamada,
Hodaka Saito,
Masaya Araki,
Yuhei Tsuchimoto,
Shin-ichi Muroi,
Kyohei Suzuki,
Kazufumi Toume,
Jun-Dal Kim,
Takashi Matsuzaka,
Hirohito Sone,
Hitoshi Shimano,
Yoshimi Nakagawa

Affiliations

Yasunari Yamada: Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
Hodaka Saito: Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
Masaya Araki: Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Yuhei Tsuchimoto: Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
Shin-ichi Muroi: Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
Kyohei Suzuki: Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
Kazufumi Toume: Section of Pharmacognosy, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
Jun-Dal Kim: Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
Takashi Matsuzaka: Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Hirohito Sone: Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata 951-8510, Japan
Hitoshi Shimano: Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Yoshimi Nakagawa: Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan

DOI: https://doi.org/10.3390/nu14193920
Journal volume & issue: Vol. 14, no. 19
p. 3920

Abstract

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Fibroblast growth factor 21 (FGF21), which is mainly synthesized and secreted by the liver, plays a crucial role in systemic glucose and lipid metabolism, ameliorating metabolic diseases. In this study, we screened the WAKANYAKU library derived from medicinal herbs to identify compounds that can activate Fgf21 expression in mouse hepatocyte AML12 cells. We identified Scutellaria baicalensis root extract and one of its components, wogonin, as an activator of Fgf21 expression. Wogonin also enhanced the expression of activating transcription factor 4 (ATF4) by a mechanism other than ER stress. Knockdown of ATF4 by siRNA suppressed wogonin-induced Fgf21 expression, highlighting its essential role in wogonin’s mode of action. Thus, our results indicate that wogonin would be a strong candidate for a therapeutic to improve metabolic diseases by enhancing hepatic FGF21 production.

Published in Nutrients

ISSN: 2072-6643 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Home economics: Nutrition. Foods and food supply
Website: https://www.mdpi.com/journal/nutrients

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