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已发表论文
SIRT1 的增强对于米歇利醇在四氯化碳诱导的小鼠肝纤维化中发挥抗炎作用是必需的
Authors Jin C, Jiang A, Chang J, Hu Y, Wang Y, Zhao R, Shi J, Wu H, Han Z, Liu Z
Received 7 August 2025
Accepted for publication 12 November 2025
Published 19 November 2025 Volume 2025:18 Pages 16231—16245
DOI https://doi.org/10.2147/JIR.S559076
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Fatih Türker
Chengye Jin,1,* Aoqing Jiang,1,* Jieming Chang,1 Yirong Hu,1 Yichen Wang,1 Rui Zhao,1 Jingwei Shi,2 Hongyan Wu,3 Zhongliang Han,1 Zhaoguo Liu1
1School of Pharmacy, Nantong University, Nantong, Jiangsu, People’s Republic of China; 2School of Medicine, Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Institute of Biomedical Technology, Jiangsu Medical College, Yancheng, Jiangsu, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhaoguo Liu, School of Pharmacy, Nantong University, Nantong, Jiangsu, People’s Republic of China, Tel +86 513 8505 1726, Fax +86 513 8505 1728, Email lzg871014@ntu.edu.cn
Purpose: Micheliolide (MCL), a guaianolide sesquiterpene lactone isolated from Michelia compressa and Michelia champaca, exhibits diverse pharmacological activities, with particularly potent hepatoprotective effects. However, research on its effects against liver fibrosis and underlying mechanisms remains limited. This study aimed to investigate the protective role of MCL in carbon tetrachloride (CCl4)-induced liver fibrosis in mice and elucidate the potential mechanisms, with a focus on the regulation of Sirtuin 1 (SIRT1).
Methods: Liver fibrosis model was established in mice via intraperitoneal (i.p.) injections of 10% CCl4. Serum biochemical indicators and liver fibrosis biomarkers were investigated. Liver collagen deposition was assessed by Masson and Sirus red staining. Protein and inflammatory cytokine expression levels were assessed using qRT-PCR, Western blot, ELISA, Immunohistochemistry staining, and Tissue immunofluorescence assays.
Results: MCL attenuated CCl4-induced liver injury and restored hepatic function in mice. Mechanistically, MCL reduced liver collagen deposition, downregulated the protein expression of α-smooth muscle actin (α-SMA) and fibronectin in liver tissues, and decreased serological markers of liver fibrosis. Additionally, MCL suppressed the serum levels of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) while increasing IL-10 levels. Notably, CCl4 administration caused a significant reduction in SIRT1 protein and mRNA expression, which was markedly reversed by MCL treatment. The selective SIRT1 inhibitor EX-527 abrogated both the anti-liver injury and anti-fibrotic effects of MCL. Moreover, EX-527 also attenuated MCL-mediated suppression of liver inflammation in CCl4-induced fibrotic mice.
Conclusion: MCL mitigates CCl4-induced liver injury and fibrosis by activating SIRT1 to suppress liver inflammation in mice. These findings uncover a novel molecular mechanism for the anti-liver fibrotic activity of MCL and highlight its potential as a therapeutic candidate for liver fibrosis.
Keywords: micheliolide, carbon tetrachloride, liver fibrosis, inflammation, SIRT1
1School of Pharmacy, Nantong University, Nantong, Jiangsu, People’s Republic of China; 2School of Medicine, Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Institute of Biomedical Technology, Jiangsu Medical College, Yancheng, Jiangsu, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhaoguo Liu, School of Pharmacy, Nantong University, Nantong, Jiangsu, People’s Republic of China, Tel +86 513 8505 1726, Fax +86 513 8505 1728, Email lzg871014@ntu.edu.cn
Purpose: Micheliolide (MCL), a guaianolide sesquiterpene lactone isolated from Michelia compressa and Michelia champaca, exhibits diverse pharmacological activities, with particularly potent hepatoprotective effects. However, research on its effects against liver fibrosis and underlying mechanisms remains limited. This study aimed to investigate the protective role of MCL in carbon tetrachloride (CCl4)-induced liver fibrosis in mice and elucidate the potential mechanisms, with a focus on the regulation of Sirtuin 1 (SIRT1).
Methods: Liver fibrosis model was established in mice via intraperitoneal (i.p.) injections of 10% CCl4. Serum biochemical indicators and liver fibrosis biomarkers were investigated. Liver collagen deposition was assessed by Masson and Sirus red staining. Protein and inflammatory cytokine expression levels were assessed using qRT-PCR, Western blot, ELISA, Immunohistochemistry staining, and Tissue immunofluorescence assays.
Results: MCL attenuated CCl4-induced liver injury and restored hepatic function in mice. Mechanistically, MCL reduced liver collagen deposition, downregulated the protein expression of α-smooth muscle actin (α-SMA) and fibronectin in liver tissues, and decreased serological markers of liver fibrosis. Additionally, MCL suppressed the serum levels of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) while increasing IL-10 levels. Notably, CCl4 administration caused a significant reduction in SIRT1 protein and mRNA expression, which was markedly reversed by MCL treatment. The selective SIRT1 inhibitor EX-527 abrogated both the anti-liver injury and anti-fibrotic effects of MCL. Moreover, EX-527 also attenuated MCL-mediated suppression of liver inflammation in CCl4-induced fibrotic mice.
Conclusion: MCL mitigates CCl4-induced liver injury and fibrosis by activating SIRT1 to suppress liver inflammation in mice. These findings uncover a novel molecular mechanism for the anti-liver fibrotic activity of MCL and highlight its potential as a therapeutic candidate for liver fibrosis.
Keywords: micheliolide, carbon tetrachloride, liver fibrosis, inflammation, SIRT1