Deglycosylation of Plant Compounds Alters Suitability as Substrates for Hepatic CYP Enzymes
Faculty Mentor Information
Dr. Carolyn Dadabay, College of Idaho
Presentation Date
7-16-2026
Abstract
Herbivorous vertebrates tolerate chemically complex compounds (xenobiotics) by using liver detoxification enzymes, including the cytochrome-P450 (CYP) enzyme family. Before xenobiotics are absorbed and circulated to the liver, they can be metabolized by the gut microbiome which cleaves sugar moieties to liberate aglycones. This modification reduces hydrophilicity before these compounds reach the liver. We hypothesized that microbiome action increases the suitability of xenobiotics as substrates for hepatic CYP enzymes. Refining sample preparation to reflect these biotransformations may improve the practical relevance of in vitro findings. In this study, the activity of herbivore liver CYPs in vitro using red willow (Salix laevigata) plant extract as substrate was compared with and without pre-treatment of the substrates with pectinase to mimic microbial glycosidase action. A series of glycosylated and aglycone individual substrates were also compared. LC-MS analysis revealed clear differences between pectinase-treated and untreated plant extracts. Less polar aglycone products were generated, indicating that the pectinase treatment altered compounds in the plant extract in a manner consistent with the cleavage of glycosidic bonds. These findings underscore the importance of accounting for gut microbial activity when predicting hepatic responses to dietary compounds. As research in plant-based pharmaceuticals continues to grow, ensuring that assays are digestion-informed may more accurately predict clinical outcomes, facilitating the transition from research to practical applications.
Deglycosylation of Plant Compounds Alters Suitability as Substrates for Hepatic CYP Enzymes
Herbivorous vertebrates tolerate chemically complex compounds (xenobiotics) by using liver detoxification enzymes, including the cytochrome-P450 (CYP) enzyme family. Before xenobiotics are absorbed and circulated to the liver, they can be metabolized by the gut microbiome which cleaves sugar moieties to liberate aglycones. This modification reduces hydrophilicity before these compounds reach the liver. We hypothesized that microbiome action increases the suitability of xenobiotics as substrates for hepatic CYP enzymes. Refining sample preparation to reflect these biotransformations may improve the practical relevance of in vitro findings. In this study, the activity of herbivore liver CYPs in vitro using red willow (Salix laevigata) plant extract as substrate was compared with and without pre-treatment of the substrates with pectinase to mimic microbial glycosidase action. A series of glycosylated and aglycone individual substrates were also compared. LC-MS analysis revealed clear differences between pectinase-treated and untreated plant extracts. Less polar aglycone products were generated, indicating that the pectinase treatment altered compounds in the plant extract in a manner consistent with the cleavage of glycosidic bonds. These findings underscore the importance of accounting for gut microbial activity when predicting hepatic responses to dietary compounds. As research in plant-based pharmaceuticals continues to grow, ensuring that assays are digestion-informed may more accurately predict clinical outcomes, facilitating the transition from research to practical applications.