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

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.

Exploring the effect of Yinzhihuang granules on alcoholic liver disease based on pharmacodynamics, network pharmacology and molecular docking

“…When a large amount of oxides accumulate in the body and liver cells cannot be cleared in a timely manner, it can lead to lipid peroxidation reactions in the liver cell membrane, causing liver cell inflammation, fatty degeneration, inflammatory cell infiltration, and even liver cell necrosis [ 41 ]. When liver cells were damaged, AST and ALT levels in the body will increase [ 42 ]. This study showed that YZHG can reduce AST and ALT levels in ALD mice, indicating that YZHG has a certain protective effect on liver damage.…”

Polyphenols from the Peels of Punica granatum L. and Their Bioactivity of Suppressing Lipopolysaccharide-Stimulated Inflammatory Cytokines and Mediators in RAW 264.7 Cells via Activating p38 MAPK and NF-κB Signaling Pathways

“…As described in the literature, corilagin ( 16 ) could restrict M1 macrophage activation by regulating the MAPK, NF-κB and interferon regulatory factor signaling pathways, resulting in a reduction in the expression of pro-inflammatory cytokines, such as IL-6, IL-12 and iNOS [ 37 ]. In addition, punicalin ( 18 ) reduced the release of inflammatory factors, including IL-1β and IL-18, via the ROS/NLRP3 pathway to exert anti-inflammatory function [ 38 ].…”

Hydrolysable tannins as a potential therapeutic drug for the human fibrosis‐associated disease

“…In addition, another study also indicated that corilagin may ameliorate hepatic injury by connecting with macrophages and preventing M1 macrophage polarization in concanavalin A-induced acute immunemediated hepatitis (Yan et al, 2021). MicroRNA-21 (miR-21) was highly expressed in fibrotic disease through targeting Smad7 in the liver, activating HSCs, and producing ECM proteins (Wei et al, 2013).…”

“…fibrosis (Chu et al, 2016;Du et al, 2016;Go et al, 2016;Huang et al, 2013;Li et al, 2016;Rajasekar et al, 2020;Rong et al, 2018). By modulating macrophages polarization, HT inhibited LPS-induced M1 macrophages polarization in lung epithelial cells and decreased the activation of M1 macrophages in the hepatic mononuclear cells to alleviate fibrosis (Du et al, 2016;Li et al, 2017;Yan et al, 2021). HT could attenuate CCl 4 -induced liver fibrosis by suppressing tumor necrosis factorα downstream signaling pathway (Go et al, 2016).…”