Astragaloside IV pretreatment enhances the therapeutic efficacy of bone marrow mesenchymal stem cells in murine fulminant hepatic failure.

OBJECTIVE

This study evaluated the effects of Huangqi injection (HQI), a standardized Astragalus extract, on the viability and regenerative potential of bone marrow-derived stem cells (BMSCs) in a D-galactosamine and lipopolysaccharide (D-GalN/LPS)-induced mouse model of FHF.

METHODS

BMSCs were cultured in medium supplemented with HQI to generate HQI-treated BMSCs (HQI-BMSCs). Cell viability was assessed using the CCK-8 assay. A murine FHF model was established by intraperitoneal injection of D-GalN/LPS, followed by immediate tail vein transplantation of BMSCs or HQI-BMSCs. Mice were randomly assigned to four groups: normal control, D-GalN + LPS (FHF), D-GalN + LPS + BMSCs, and D-GalN + LPS + HQI-BMSCs. At 4 h post-transplantation, serum levels of alanine aminotransferase (ALT), total bilirubin (TBIL), interleukin-10 (IL-10), and interleukin-6 (IL-6) were measured. Liver tissue was collected for hematoxylin-eosin staining to assess histopathological injury, TUNEL assay to evaluate hepatocyte apoptosis, and immunohistochemistry to detect proliferating cell nuclear antigen (PCNA)-positive cells. PCNA protein expression was further quantified by western blotting. To investigate the contribution of active constituents, BMSCs were also pretreated with AS-IV, a principal bioactive compound in HQI, and effects on stemness-related gene expression, cell cycle progression, and LPS-induced apoptosis were assessed.

RESULTS

HQI treatment markedly improved BMSC viability. In the FHF model, HQI-BMSC transplantation reduced serum ALT, TBIL, and IL-6 levels, and suppressed hepatocyte apoptosis in liver tissue. Furthermore, AS-IV enhanced the expression of stemness-related genes in BMSCs, promoted G1-to-S/G2 phase progression, and attenuated LPS-induced apoptosis in BMSCs. HQI-BMSCs conferred greater hepatoprotective effects than untreated BMSCs, as evidenced by improved biochemical indices and reduced histopathological damage.

CONCLUSION

Bioactive constituents of Astragalus membranaceus preconditioning enhanced the viability, stemness, and therapeutic efficacy of BMSCs in FHF, supporting their use as a potentiated stem cell-based intervention.