3-Hydroxybufadienolides in Bufo gallbladders: structural insights and biotransformation

Bufadienolides, naturally occurring steroids primarily found in toads, have garnered attention for their pharmacological properties and ecological significance. In this study, we isolated and identified 21 bufadienolides from the gallbladders of Bufo gargarizans, comprising four new compounds and 17 known ones. Notably, the predominance of 15 bufadienolides with a 3 alpha-OH configuration in toad bile differs significantly from the 3 beta-OH bufadienolides found in venom secreted by toad glands. Moreover, our investigation into the biotransformation of 3 beta-OH and 3 alpha-OH bufadienolides in the liver and kidney tissues of toads revealed an irreversible conversion from 3 beta-OH to 3 alpha-OH bufadienolides, suggesting a crucial role in toad self-detoxification. These findings provide valuable insights into the structural diversity of bufadienolides and advance our understanding of their medical and ecological significance.