Background: We administered Bushen Huoxue Huazhuo Formula (BSHXHZF) and transplanted bone marrow mesenchymal stem cells (BMSCs) into mice with Wilson's disease (WD)-related liver fibrosis to evaluate the liver-protecting mechanism of this prescription.
Methods: Mice, randomly divided into different treatment groups, showed histopathological changes and degree of hepatocyte apoptosis. For hepatic hydroxyproline (Hyp) determination, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) mRNA and protein were measured. Chemical profiling of the extract of BSHXHZF using The liquid chromatography-mass spectrometry (LC-MS/MS) and revealing its antifibrosis mechanism using metabolomics.
Results: TCM+BMSC group livers exhibited few inflammatory cells. TUNEL revealed abundant brown apoptotic cells in model control groups, while the TCM+BMSC groups showed a significant increase in blue negative expression of liver cells. Hyp in toxic milk (TX) mice groups was significantly lower than that in model control groups (MG). Compared with MG, TGF-β1 expression was significantly lower than all other groups, while BMP-7 expression was significantly higher. Metabolic analysis identified 20 potential biomarkers and 10 key pathways, indicating that BSHXHZF+BMSC intervention has a significant regulatory effect on metabolic disorders of these small molecule substances.
Conclusion: BSHXHZF combined with BMSCs can inhibit liver fibrosis and hepatocyte apoptosis by improving related metabolic disorders, and achieving therapeutic effects in WD-related liver fibrosis.
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