Abstract

Context

Our previous studies indicated that Yiguanjian decoction (YGJ) has an anti-hepatic-fibrosis effect and could regulate macrophage status.

Objective

To elucidate the mechanism of YGJ in regulating macrophages.

Materials and methods

Liver cirrhosis was induced by CCl4 for 12 weeks combined with 2-acetylaminofluorene (2-AAF) for the last 4 weeks in male Wistar rats. YGJ (3.56 mg/kg) orally administered in the last 4 weeks, and SORA (1 mg/kg) as control. In vitro, RAW264.7 cells were treated with lipopolysaccharides (LPSs) to induce macrophage polarization to the M1 phenotype, and they were co-cultured with WB-F344 cells and allocated to M group, YGJ group (2 μg/mL) and WIF-1 group (1 μg/mL) with untreated cells as control. The differentiation direction of WB-F344 cell line was observed in the presence or absence of YGJ. Pathology, fibrosis-related cytokines, macrophage polarization-related components, and Wnt signalling pathway components were detected.

Results

In vivo, the expression levels of α-SMA, Col (1), OV6, SOX9, EpCAM and M1 macrophage-related components (STAT1, IRF3, IRF5, IRF8, SOCS3) significantly decreased in the YGJ group compared with those in the 2-AAF/CCl4 group (p < 0.01 or 0.05). In vitro, the expression levels of M1 macrophage-related components, including STAT1, NF-κB, IRF3, IRF5, and SOCS3, in RAW264.7 cells decreased significantly in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01). The expression levels of Wnt3A, FZD5, LRP-5/-6, and β-catenin significantly increased in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01). In addition, the expression levels of Wnt-4/-5A/-5B, and FZD2 significantly decreased in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01).

Conclusion

This study suggests that the anti-cirrhosis effect of YGJ is associated with its ability to inhibit macrophage M1-polarization, which provides a scientific basis for the clinical application of YGJ.

Details

Title
Yiguanjian decoction inhibits macrophage M1 polarization and attenuates hepatic fibrosis induced by CCl4/2-AAF
Author
Xu, Ying 1 ; Xu, Wen 1 ; Liu, Wei 1 ; Chen, Gaofeng 2 ; Jiang, Shili 1 ; Chen, Jiamei 2 ; Xun Jian 1 ; Zhang, Hua 2 ; Liu, Ping 3 ; Mu, Yongping 2 

 Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, Pudong District, China; Institute of Liver Diseases, Shanghai University of TCM, Shanghai, China 
 Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, Pudong District, China; Institute of Liver Diseases, Shanghai University of TCM, Shanghai, China; Key Laboratory of Liver and Kidney Disease of the Ministry of Education, Shanghai, China 
 Institute of Liver Diseases, Shanghai University of TCM, Shanghai, China; Key Laboratory of Liver and Kidney Disease of the Ministry of Education, Shanghai, China; Clinical Key Laboratory of TCM of Shanghai, Shanghai, Pudong District, China 
Pages
1148-1158
Publication year
2021
Publication date
Dec 2021
Publisher
Taylor & Francis Ltd.
ISSN
13880209
e-ISSN
17445116
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2691137958
Copyright
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.