Sini Powder Alleviates Stress Response and Suppresses Hepatocellular Carcinoma Development by Restoring Gut Microbiota (original) (raw)

Abstract

Objectives

To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC).

Methods

The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice.

Results

The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased.

Conclusion

SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.

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Authors and Affiliations

  1. Faculty of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
    Si Mei
  2. College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
    Zhe Deng, Fan-ying Meng, Qian-qian Guo, He-yun Tao, Lin Zhang & Xue-fei Tian
  3. School of Humanities and Management, Hunan University of Chinese Medicine, Changsha, 410208, China
    Chang Xi
  4. The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, China
    Qing Zhou
  5. Faculty of International Education, Hunan University of Chinese Medicine, Changsha, 410208, China
    Xue-fei Tian

Authors

  1. Si Mei
  2. Zhe Deng
  3. Fan-ying Meng
  4. Qian-qian Guo
  5. He-yun Tao
  6. Lin Zhang
  7. Chang Xi
  8. Qing Zhou
  9. Xue-fei Tian

Contributions

Mei S conceived and designed the experiments. Deng Z, Meng FY and Guo QQ performed the experiments. Tao HY, Zhang L and Xi C analyzed the data. Mei S, Zhou Q and Tian XF contributed to the writing of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Xue-fei Tian.

Ethics declarations

The authors declare no competing financial interest.

Additional information

Supported by Natural Science Foundation of Hunan Province (No. 2023JJ40481), funding from the Education Department of Hunan Province (No. 21B0374), and funding from the Hunan University of Chinese Medicine (No. 2024XJZA001)

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Mei, S., Deng, Z., Meng, Fy. et al. Sini Powder Alleviates Stress Response and Suppresses Hepatocellular Carcinoma Development by Restoring Gut Microbiota.Chin. J. Integr. Med. 31, 802–811 (2025). https://doi.org/10.1007/s11655-025-4127-z

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