Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis

Zhurong LI; Chen CHEN; Di GUO; Sixue LYU; Jiawen WU; Na YANG; Yang LIU

doi:10.12449/JCH240311

Volume 40 Issue 3

Mar. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(3): 502-508

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Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis

DOI: 10.12449/JCH240311

School of Basic Medical Sciences，Shanxi University of Chinese Medicine，Jinzhong，Shanxi 030619，China

Research funding:

Shanxi Provincial Key Country Science and Technology Cooperation Project Shanxi Provincial Science and Technology Department (202104041101013);

Science and Technology Innovation Team Project of Shanxi University of Traditional Chinese Medicine (2022TD2003);

Key Team of Science and Technology Innovation Talents of Shanxi Province for Prevention and Treatment of Rheumatological and Immunological diseases by Integrated Chinese and Western Medicine (202204051002033);

Discipline Construction Project of Shanxi University of Traditional Chinese Medicine (2023XKJS-03);

Natural Science Foundation Project of Shanxi Province (202203021222272)

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Corresponding author: LIU Yang， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）
Received Date: 2023-06-09
Accepted Date: 2023-08-15
Published Date: 2024-03-20

Abstract

Abstract

Objective To investigate the role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis. Methods A total of 18 specific pathogen-free female C57BL/6 mice were selected and divided into normal group， model group， and treatment group using a random number table， with 6 mice in each group. The mice in the model group and the treatment group were injected with concanavalin A （Con A） via the caudal vein to establish a mouse model of autoimmune hepatitis， and those in the normal group were injected with normal saline. The mice in the treatment group were given prophylactic treatment with Yinchenhao Decoction （4.68 g crude drug/kg） by gavage at 14 days before modeling， and Con A was injected after the last gavage. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interferon gamma （IFN-γ）， tumor necrosis factor-α （TNF-α）， iron ion， glutathione （GSH）， reactive oxygen species （ROS）， adenosine triphosphate （ATP）， and malondialdehyde （MDA） were measured； liver index and spleen index were calculated； the expression levels of GPX4 and SLC7A11 were measured； liver histopathological changes were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the least significant difference t-test was used for further comparison between two groups. Results Compared with the normal group， the model group had significant increases in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant reductions in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. Compared with the model group， the treatment group had significant reductions in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant increases in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. HE staining showed that compared with the normal group， the model group showed massive hepatocyte degeneration and necrosis and inflammatory cell aggregation at the portal area， and compared with the model group， the treatment group had alleviation of liver necrosis and inflammatory infiltration. Conclusion Liver injury induced by Con A may be associated with ferroptosis. Yinchenhao Decoction can increase the protein expression levels of SLC7A11 and GPX4 protein and thus inhibit ferroptosis of hepatocytes induced by Con A.
- Hepatitis， Autoimmune,
- Yinchenhao Decoction,
- Ferroptosis,
- Glutathione Peroxidase,
- Mice， Inbred C57BL

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Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis

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Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis

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