Biotransformation and its effects on anxiolytic activity and toxicity of Polygalae Radix saponins.

Saponins, accounting for over 2.0% (w/w) in Polygalae Radix extracts, act as both active and toxic constituents, with their glycosyl structures hypothesized to modulate efficacy and toxicity. This study aimed to modify the glycosyl structures of Polygalae Radix (PR) saponins via snail enzyme biotransformation and evaluate changes in the activity of inhibiting anxiety-like behavior in the EPM and gastrointestinal toxicity. The biotransformation process was optimized using one-way experiments and response surface methodology, identifying optimal conditions as 46 °C, pH 6.4, 72-h reaction time, and an enzyme-substrate ratio of 25:1. UPLC-Q-Exactive/MS analysis revealed 37 differential saponin-like components with truncated glycosyl chains. In the elevated plus-maze (EPM) test, both untransformed and transformed PR saponins exhibited a significant effect of inhibiting anxiety-like behavior in the EPM, with transformed products showing enhanced activity. Gastrointestinal toxicity assessments, including weight monitoring and gastric tissue morphology observation, demonstrated reduced flatulence and weight loss in mice administered transformed saponins. These results confirm that glycosyl chain degradation in PR saponins reduces gastrointestinal toxicity while preserving the efficacy of inhibiting anxiety-like behavior in the EPM, providing a scientific basis for improving the safety and clinical application of PR.