Protective effect of quercetin against macrophage-mediated hepatocyte injury via anti-inflammation, anti-apoptosis and inhibition of ferroptosis

Abstract

Yinchenhao Decoction (YCHD) is a classic prescription in traditional Chinese medicine (TCM). It appears to play an important role in anti-inflammation and autoimmunity protection. As one of the key active ingredients in YCHD, quercetin is a novel anti-inflammatory metabolite that exerts protective effects in many autoimmune diseases. However, its role in autoimmune hepatitis (AIH)-related hepatic injury has not been studied. The aim of this study was to reveal the hepatocyte protective mechanism of quercetin. In this study, we used Concanavalin A (Con A) to establish an in vitro hepatocyte injury-associated AIH model. Brl3a hepatocyte injury was induced by the supernatant of J774A.1 cells treated with Con A. We found that quercetin mitigated Con A-induced via macrophage-mediated Brl3a hepatocyte injury. Quercetin administration reduced the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in the supernatant of Con A-treated Brl3a cells and attenuated the infiltration of J774A.1 macrophages induced by Con A. Moreover, quercetin effectively inhibited the expression of proinflammatory cytokines including interleukin-1β (IL-1β) by Con A. Furthermore, quercetin decreased hepatocyte apoptosis and ferroptosis levels in the macrophage-induced hepatocyte injury model. In conclusion, our study indicates that quercetin alleviates macrophage-induced hepatocyte damage by reducing the inflammatory response, apoptosis and ferroptosis. Our work suggests that quercetin might be a potential therapeutic strategy for AIH.

Keywords:

• Autoimmune hepatitis
• Yinchenhao decoction
• quercetin
• apoptosis
• ferroptosis

Author contributions

Yang Liu and Tiezheng Hou conceived and designed the project. Yiwen Hou completed the main experiments, wrote the paper and analyzed the data. Chen Chen, Zhurong Li Jiawen Wu, Sixue Lyu, Di Guo and Ying Liu assisted in conducting the experiments and analyzing the data. Yang Liu and Tiezheng Hou critically revised the manuscript.

Disclosure statement

No potential competing interest was reported by the authors.

Data availability statement

The data that supports the findings of this study is available from the corresponding author upon reasonable request.

Additional information

Funding

We thank the funding organizations Basic research of integrated Chinese and Western medicine on rheumatic immune diseases (Grant Number: 2023XKJS-03), Prevention and treatment of rheumatism and immune disease by combination of traditional Chinese and Western medicine Shanxi scientific and technological innovation talent team project (Grant Number: 202204051002033), Science and Technology Innovation Project of Shanxi University of Chinese Medicine (Grant Number: 2022TD2003) and Special project of scientific and technological cooperation and exchange in Shanxi Province (Grant Number: 202104041101013). The Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine.