Influence of substrates on the in vitro kinetics of steviol glucuronidation and interaction between steviol glycosides metabolites and UGT2B7

Abstract

Steviol glycosides, a natural sweetener, may perform bioactivities via steviol, their main metabolite in human digestion. The metabolising kinetics, i.e. glucuronidation kinetics and interaction between steviol glycosides or their metabolites and metabolising enzyme, are important for understanding the bioactivity and cytotoxicity. The present study investigated kinetics of steviol glucuronidation in human liver microsome and a recombinant human UDP-glucuronosyltransferases isomer, UGT2B7, along with molecular docking to analyse interaction between UGT2B7 and steviol or glucose. The active pocket of UGT2B7 is consisted of Arg352, Leu347, Lys343, Phe339, Tyr354, Lys355 and Leu353. The influence of stevioside, rebaudioside A, glucose and some chemotherapy reagents on the glucuronidation was also studied. The predicted hepatic clearence suggested that steviol could be classified as high-clearence drug. The steviol glycosides did not affect the glucuronidation of steviol notably.

Keywords:

• Steviol
• glucuronidation
• UGT2B7
• hepatic clearance
• molecular docking

Acknowledgements

Specific appreciations to the reviewers and editor, their helpful and smart comments should have made them coauthorship for this article.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

Financial support from National Natural Science Foundation of China [31371837, 31772017] and the project of outstanding scientific & technological innovation group of Jiangsu Province are gratefully appreciated.