- herb pair in the progression of hepatitis, cirrhosis, and hepatocellular carcinoma: a possible mechanisms and relevant therapeutic substances.

BACKGROUND

Both (SF) and (AM) are known for their anti-inflammatory, antifibrotic, and anticancer activities. However, the efficacy, multi-target mechanisms, and therapeutic substances of SF-AM herb pair on the progression of hepatitis-cirrhosis-hepatocellular carcinoma hepatocellular carcinoma (HCC) remain unclear.

PURPOSE

To investigate the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the progression of hepatitis-cirrhosis-HCC.

METHODS

Firstly, diethylnitrosamine was used to establish the hepatitis-cirrhosis-HCC model. HE staining and non-targeted metabolomics were used to evaluate the efficacy of SF-AM herb pair. Subsequently, the absorbed components of SF-AM herb pair in the plasma of rats were determined through HPLC-Q-TOF-MS/MS analysis. Flow cytometry, Western blot, and qRT-PCR were then employed to assess CD4 and CD8 T lymphocytes, PI3K/Akt signaling pathway-related proteins, and their corresponding mRNAs. Simultaneously, the efficacy and mechanism of SF-AM herb pair on HCC were confirmed by experiments. Finally, Pearson correlation analysis was performed between pharmacodynamic indicators and components to identify the potential therapeutic substances of SF-AM herb pair.

RESULTS

SF-AM herb pair can alleviate the pathological damage and reverse metabolic abnormalities in hepatitis, cirrhosis, and HCC rats, particularly during the hepatitis and cirrhosis stages. Pharmacological researches have demonstrated that SF-AM herb pair can increase the proportion of CD8 T lymphocytes, inhibit the expression of PI3K, Akt, p-Akt, NF-κB p65, NF-κB pp65, and Bcl-2, as well as increase the expression of IκBα, Bax, and cleaved caspase-3. These findings suggest that SF-AM herb pair has the ability to enhance immunity, anti-inflammation and promote apoptosis. Cell experiments have shown that SF-AM herb pair can inhibit the proliferation of HepG2 cell and regulate the PI3K/Akt signaling pathway. Moreover, 23 absorbed prototypical components and 53 metabolites of SF-AM herb pair were identified at different stages of HCC rats. Pearson correlation analysis revealed that matrine, cytisine, wogonoside, and isoastragaloside are potential therapeutic substances in SF-AM herb pair for the prevention and treatment of hepatitis, cirrhosis, and HCC.

CONCLUSION

In summary, this study revealed the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the hepatitis-cirrhosis-HCC axis and provided a reference for its clinical application.