Cultured mycelia of Cordyceps sinensis exerts a protective effect on a mouse model of liver fibrosis by inhibiting the Toll-like receptor 4/nuclear transcription factor-κB signaling pathway and angiopoietin-like protein 4

Linzhang ZHANG; Dingqi ZHANG; Ying XU; Hailin YANG; Shenglan QI; Congcong ZHANG; Jiamei CHEN; Ping LIU; Wei LIU

doi:10.3969/j.issn.1001-5256.2022.07.016

Volume 38 Issue 7

Jul. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(7): 1540-1547

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Cultured mycelia of Cordyceps sinensis exerts a protective effect on a mouse model of liver fibrosis by inhibiting the Toll-like receptor 4/nuclear transcription factor-κB signaling pathway and angiopoietin-like protein 4

DOI: 10.3969/j.issn.1001-5256.2022.07.016

Linzhang ZHANG^{1, 2a},
Dingqi ZHANG¹,
Ying XU^{1, 2b},
Hailin YANG¹,
Shenglan QI^2a,
Congcong ZHANG¹,
Jiamei CHEN¹,
Ping LIU^{1, 2a
,
,
,},
Wei LIU^{1
,
,
,}

1.
Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2a.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2b.
Teaching and Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Research funding:

"Chen Guang" Project Supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (20CG50);

Young Elite Scientists Sponsorship Program by CAST (2020QNRC001);

National Natural Science Foundation of China (81530101);

National Natural Science Foundation of China (82004162);

Shanghai Science and Technology Innovation Action Plan (20S21902600);

Shanghai Sailing Program (20YF14495000);

China Postdoctoral Science Foundation (2020M681367)

More Information

Corresponding author: LIU Ping, liuliver@vip.sina.com(ORCID: 0000-0002-6152-4508); LIU Wei, lwhzayl@163.com(ORCID: 0000-0002-7284-0936)
Received Date: 2021-11-18
Accepted Date: 2021-12-21
Published Date: 2022-07-20

Abstract

Abstract

Objective To investigate the interventional effect of cultured mycelia of Cordyceps sinensis on a mouse model of CCl₄-induced liver fibrosis and its effect on the Toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) pathway and angiopoietin-like protein 4 (ANGPTL4). Methods A total of 60 specific pathogen-free male C57/BL6J mice were randomly divided into normal group, model group, Fuzheng Huayu group, and low-, middle-, and high-dose Cordyceps sinensis groups, with 10 mice in each group. The mice in the model group and each medication group were intraperitoneally injected with 15% CCl₄-olive oil for 6 weeks of modeling, and drug intervention was started on the first day of week 4 and lasted for 3 consecutive weeks. Blood biochemistry was used to measure the serum level or activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil); HE and SR staining was used to observe liver histopathology; alkaline hydrolysis was used to measure the content of hydroxyproline (HYP) in liver tissue; PCR was used to measure the mRNA expression of alpha-smooth muscle actin (α-SMA) and collagen type Ⅰ (Col-Ⅰ), immunohistochemistry was used to measure the protein expression of α-SMA, Col-Ⅰ, and ANGPTL4 in liver tissue, and Western blot (WB) was used to measure the protein expression of α-SMA, ANGPTL4, TLR4, NF-κB/phosphorylated NF-κB (P-NF-κB), and CD163. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the LSD-t test was used for further comparison between two groups. Results Compared with the normal group, the model group had significant increases in the serum levels of ALT, AST, and TBil (all P < 0.01), and compared with the model group, the high-dose Cordyceps sinensis group had a significant improvement in the degree of liver fibrosis and significant reductions in the serum levels of ALT, AST, and TBil (all P < 0.05). HE staining revealed that the high-dose Cordyceps sinensis group had a significant reduction in inflammatory cell infiltration in liver tissue, and SR staining showed that high-dose Cordyceps sinensis significantly alleviated collagen deposition in the liver tissue. Compared with the normal group, the model group had significant increases in HYP content and Sirius red-positive area ratio in liver tissue (both P < 0.01), and compared with the model group, the high-dose Cordyceps sinensis group had significant reductions in HYP content and Sirius red-positive area ratio (both P < 0.05). Compared with the normal group based on the results of immunohistochemistry, PCR, and WB, the model group had significant increases in the mRNA and protein expression levels of α-SMA and Col-Ⅰ in liver tissue (all P < 0.01), and compared with the model group, the high-dose Cordyceps sinensis group had significant reductions in the expression levels of α-SMA and Col-Ⅰ(P < 0.05). Compared with the normal group, the model group had significant increases in the protein expression of ANGPTL4, TLR4, P-NF-κB/NF-κB, and CD163 in liver tissue (all P < 0.01), and compared with the model group, the high-dose Cordyceps sinensis group had significant reductions in the protein expression of ANGPTL4, TLR4, P-NF-κB/NF-κB, and CD163 in liver tissue (all P < 0.05). Conclusion Cordyceps sinensis mycelia have a marked therapeutic effect on CCl₄-induced liver fibrosis in mice, possibly by regulating the TLR4/NF-κB signaling pathway and inhibiting ANGPTL4 expression in liver tissue.
- Liver Cirrhosis,
- Angiopoietins,
- Toll-Like Receptor 4,
- NF-kappa B

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References(26)

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Cultured mycelia of Cordyceps sinensis exerts a protective effect on a mouse model of liver fibrosis by inhibiting the Toll-like receptor 4/nuclear transcription factor-κB signaling pathway and angiopoietin-like protein 4

DOI: 10.3969/j.issn.1001-5256.2022.07.016

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Cultured mycelia of Cordyceps sinensis exerts a protective effect on a mouse model of liver fibrosis by inhibiting the Toll-like receptor 4/nuclear transcription factor-κB signaling pathway and angiopoietin-like protein 4

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