Protodioscin, a natural saponin with potential steroidogenic effects: metabolic and analytical considerations

Protodioscin is a steroidal saponin naturally occurring in Tribulus terrestris, a plant widely used in traditional medicine and commercial supplements. It is often promoted for its potential to enhance physical performance, libido, and overall vitality. Nonetheless, scientific data regarding its pharmacokinetics in humans remain scarce. Understanding the metabolic biotransformation of such natural compounds is essential for assessing their pharmacological properties and for ensuring their safe use, particularly in contexts such as sports supplementation where regulatory concerns may arise. Metabolites may also serve as biomarkers of consumption. This study aimed to investigate the in-vitro metabolism of protodioscin. METHODS: The protidiosc in metabolism was studied using human hepatocyte incubations, liquid chromatography-high-resolution tandem mass spectrometry, and automated data mining. In addition, computational tools were employed to predict possible metabolic transformations to support the investigations. RESULTS: The obtained results showed no significant evidence of hepatic metabolism under the tested conditions, and no major metabolites were detected. The analysis of urine samples from individuals reporting recent ingestion of Tribulus terrestris supplements did not demonstrate the presence of metabolites related to protodioscin. DISCUSSION: These findings suggest that protodioscin may not undergo significant liver metabolism, or that it could be processed via alternative pathways, such as microbial metabolism in the gut. Further studies are necessary to elucidate the complete metabolic fate of protodioscin, to better assess its safety, efficacy, and regulatory implications, particularly in areas where its use may influence health or performance.