Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization

Fenglian Yan; Dalei Cheng; Haiyan Wang; Min Gao; Junfeng Zhang; Hongyan Cheng; Changying Wang; Hui Zhang; Huabao Xiong

doi:10.3389/fimmu.2021.807509

Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization

Front Immunol. 2022 Jan 13:12:807509. doi: 10.3389/fimmu.2021.807509. eCollection 2021.

Authors

Fenglian Yan^{1

2}, Dalei Cheng^{1

3}, Haiyan Wang^{1

2}, Min Gao⁴, Junfeng Zhang^{1

2}, Hongyan Cheng^{1

3}, Changying Wang^{1

2}, Hui Zhang^{1

2}, Huabao Xiong^{1

2}

Affiliations

¹ Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China.
² Jining Key Laboratory of Immunology, Jining Medical University, Jining, China.
³ Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ Clinical Laboratory, Jining First People's Hospital, Jining, China.

Abstract

Immune-mediated hepatic injury plays a key role in the initiation and pathogenesis of diverse liver diseases. However, treatment choice for immune-mediated hepatic injury remains limited. Corilagin, a natural ellagitannin extracted from various traditional Chinese medicines, has been demonstrated to exhibit multiple pharmacological activities, such as anti-inflammatory, anti-tumor, and hepatoprotective properties. The present study aimed to investigate the effects of corilagin on immune-mediated hepatic injury using a murine model of concanavalin A (Con A)-induced hepatitis, which is well-characterized to study acute immune-mediated hepatitis. Herein, mice were administered corilagin (25 mg/kg) intraperitoneally twice at 12 h intervals, and 1 h later, the mice were challenged with Con A (20 mg/kg body weight); serum and liver samples were collected after 12 h. The results showed that corilagin significantly increased the survival of mice and reduced serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. In addition, corilagin markedly improved histopathological damage, hepatocyte apoptosis, and oxidative stress in the liver. The activation of M1 macrophages in the hepatic mononuclear cells was also significantly reduced compared with that in the control group. The expression of M1 macrophage-associated proinflammatory cytokines and genes, including interleukin (IL)-6, IL-12, and inducible nitric oxide synthase (iNOS), was also decreased after corilagin treatment. Finally, the results demonstrated that corilagin regulated macrophage polarization by modulating the mitogen-activated protein kinases (MAPK), nuclear factor (NF)-κB, and interferon regulatory factor (IRF) signaling pathways. Thus, the findings indicate that corilagin protects mice from Con A-induced immune-mediated hepatic injury by limiting M1 macrophage activation via the MAPK, NF-κB, and IRF signaling pathways, suggesting corilagin as a possible treatment choice for immune-mediated hepatic injury.

Keywords: concanavalin A; corilagin; hepatic injury; inflammation; macrophage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Chemical and Drug Induced Liver Injury / diagnosis
Chemical and Drug Induced Liver Injury / drug therapy
Chemical and Drug Induced Liver Injury / etiology*
Chemical and Drug Induced Liver Injury / metabolism*
Concanavalin A / adverse effects*
Cytokines / metabolism
Disease Models, Animal
Disease Susceptibility
Glucosides / pharmacology*
Hydrolyzable Tannins / pharmacology*
Inflammation Mediators / metabolism
Liver Function Tests
Macrophage Activation / drug effects*
Macrophages / drug effects*
Macrophages / immunology*
Macrophages / metabolism*
Male
Mice
Treatment Outcome

Substances

Biomarkers
Cytokines
Glucosides
Hydrolyzable Tannins
Inflammation Mediators
Concanavalin A
corilagin