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CN 22-1108/R
Volume 42 Issue 2
Feb.  2026
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Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(2): 362-371

Epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer

DOI: 10.12449/JCH260216
  • 1.

    Institute of Liver Disease，The Affiliated Hospital of Hubei University of Chinese Medicine （Hubei Provincial Hospital of Traditional Chinese Medicine）；Level 3 Laboratory of Cell Molecular Biology，State Administration of Traditional Chinese Medicine；Key Laboratory of Liver and Kidney Treatment of Chronic Liver Disease，State Administration of Traditional Chinese Medicine；Hubei Key Laboratory of Theoretical and Applied Research of Liver and Kidney in Traditional Chinese Medicine，Wuhan 430061，China

  • 2.

    Science Experiment Centre for Traditional Chinese Medicine and Ethnic Medicine，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Scientific Experimental Center for Traditional Chinese Medicine and Ethnic Medicine，Nanning 530023，China

  • 3.

    Graduate School of Guangxi University of Chinese Medicine，Nanning 530001，China

Research funding:

National Natural Science Foundation of China (81973669);

National Natural Science Foundation of China (81774280);

National Natural Science Foundation of China (81703912);

National Natural Science Foundation of China (81603484);

National Natural Science Foundation of China (81573815);

National Natural Science Foundation of China (81274147);

Key Disease Research Project of the National Clinical Research Base of Traditional Chinese Medicine （Hubei） (JDZX2015172);

Li Hanmin’s Hubei Famous Traditional Chinese Medicine Master’s Transmission Studio Funding Project (Hubei Health and Family Planning Commission Document （2018） No.32);

Guangxi Zhuang Autonomous Region Traditional Chinese Medicine Administration Department’s Multi-Disciplinary Cross-Interactive Innovation Team Project for Severe Liver Diseases (GZKJ2306);

Guangxi Science and Technology Project (Guike AD17129001)

More Information
  • Corresponding author: LI Hanmin， lihanmin69@126.com （ORCID： 0000-0003-1168-0876）
  • Received Date: 2025-07-17
  • Accepted Date: 2025-11-04
  • Published Date: 2026-02-25
    Abstract
  •   Objective  To investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication.  Methods  A total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups.  Results  The DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）.  Conclusion  Abnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

     

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