Isolation of a novel bufadienolide, bufovende A, and seven known analogs from Venenum bufonis with inhibitory activity on hepatic stellate cell activation.

Abstract

As the principal bioactive constituents of Venenum Bufonis (VB), bufadienolides mediate the therapeutic efficacy of this traditional Chinese medicine in diverse clinical applications. In this study, a novel bufadienolide, designated as bufovende A (1), and seven known analogs (2-8) were isolated from VB. The structure of bufovende A was determined using spectroscopic methods (1D/2D NMR and HRESIMS). Given the pivotal role of hepatic stellate cell (HSC) activation in liver fibrogenesis, we evaluated the antifibrotic potential of these compounds using the LX-2 human HSC line. The results indicated that non-cytotoxic concentrations (0.2 μM) of bufadienolides significantly suppressed the mRNA expression of fibrosis biomarkers α-SMA and COL1A1, with bufovende A exhibiting the most pronounced inhibitory efficacy (inhibition rates of 61.33% ± 1.54% for α-SMA and 57.46% ± 12.03% for COL1A1). Additionally, compared to the model group, bufovende A downregulated α-SMA, COL1A1, and TGF-β protein expression. These results highlight the potential of bufadienolides as promising antifibrotic leads, with bufovende A being particularly promising for further investigation.