Wogonin, a Compound in Scutellaria baicalensis, 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

Wogonin, a Compound in Scutellaria baicalensis, 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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.

Original language	English
Article number	3920
Journal	Nutrients
Volume	14
Issue number	19
DOIs	https://doi.org/10.3390/nu14193920
State	Published - 2022/10

Keywords

Scutellaria baicalensis
WAKANYAKU
activating transcription factor 4
fibroblast growth factor
wogonin

ASJC Scopus subject areas

Food Science
Nutrition and Dietetics

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10.3390/nu14193920

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@article{a2aade64c117474ca2e117394af33f3f,

title = "Wogonin, a Compound in Scutellaria baicalensis, Activates ATF4–FGF21 Signaling in Mouse Hepatocyte AML12 Cells",

abstract = "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{\textquoteright}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.",

keywords = "Scutellaria baicalensis, WAKANYAKU, activating transcription factor 4, fibroblast growth factor, wogonin",

author = "Yasunari Yamada and Hodaka Saito and Masaya Araki and Yuhei Tsuchimoto and Muroi, {Shin Ichi} and Kyohei Suzuki and Kazufumi Toume and Kim, {Jun Dal} and Takashi Matsuzaka and Hirohito Sone and Hitoshi Shimano and Yoshimi Nakagawa",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = oct,

doi = "10.3390/nu14193920",

language = "英語",

volume = "14",

journal = "Nutrients",

issn = "2072-6643",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "19",

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TY - JOUR

T1 - Wogonin, a Compound in Scutellaria baicalensis, Activates ATF4–FGF21 Signaling in Mouse Hepatocyte AML12 Cells

AU - Yamada, Yasunari

AU - Saito, Hodaka

AU - Araki, Masaya

AU - Tsuchimoto, Yuhei

AU - Muroi, Shin Ichi

AU - Suzuki, Kyohei

AU - Toume, Kazufumi

AU - Kim, Jun Dal

AU - Matsuzaka, Takashi

AU - Sone, Hirohito

AU - Shimano, Hitoshi

AU - Nakagawa, Yoshimi

PY - 2022/10

Y1 - 2022/10

N2 - 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.

AB - 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.

KW - Scutellaria baicalensis

KW - WAKANYAKU

KW - activating transcription factor 4

KW - fibroblast growth factor

KW - wogonin

UR - http://www.scopus.com/inward/record.url?scp=85139841958&partnerID=8YFLogxK

U2 - 10.3390/nu14193920

DO - 10.3390/nu14193920

M3 - 学術論文

C2 - 36235573

AN - SCOPUS:85139841958

SN - 2072-6643

VL - 14

JO - Nutrients

JF - Nutrients

IS - 19

M1 - 3920

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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