Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice

Author:

Kawano Yutaka1,Tanaka Maki2,Satoh Yasushi1,Sugino Shigekazu3,Suzuki Jun3,Fujishima Masaki4,Okumura Eri4,Takekoshi Hideo4,Uehara Osamu5,Sugita Shintaro6,Abiko Yoshihiro5,Tomonari Tetsu1,Tanaka Hironori1,Takeda Hidekatsu6,Takayama Tetsuji1

Affiliation:

1. Tokushima University Graduate School of Biomedical Sciences

2. Health Sciences University of Hokkaido Hospital

3. Tohoku University School of Medicine

4. Sun Chlorella Co., Ltd

5. Health Sciences University of Hokkaido

6. Sapporo Medical University School of Medicine

Abstract

Abstract Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5 % ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score=2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.

Publisher

Research Square Platform LLC

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