Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates
Meiyu Wang1, Jia Lu1, Jiajun Li1
1College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Summary
Steviol, a metabolite of stevia sweeteners, is processed in the body through glucuronidation, mainly by UGT2B7. Diclofenac can inhibit this process, suggesting potential drug interactions.
Area of Science:
- Pharmacology
- Metabolism
- Drug Interactions
Background:
- Steviol is the active metabolite of stevia sweeteners like stevioside and rebaudioside A.
- Glucuronidation is the primary pathway for steviol clearance from the body.
- The specific enzymes (UDP-glucuronosyltransferases, UGTs) and organs involved in steviol glucuronidation are not fully understood.
Purpose of the Study:
- To identify the UGT enzymes responsible for steviol glucuronidation.
- To characterize the kinetics of steviol glucuronidation in human and rat liver and intestinal microsomes.
- To investigate potential interactions between steviol and other drugs metabolized by the identified UGTs.
Main Methods:
- Incubation of steviol with liver and intestinal microsomes from humans and rats.
- Enzyme kinetic analysis of steviol glucuronidation.
- Studies using recombinant human UGT enzymes.
- Inhibition studies with known UGT substrates, including diclofenac.
Main Results:
- Steviol glucuronidation exhibits organ specificity.
- UGT2B7 was identified as a primary enzyme for steviol glucuronidation at low concentrations, with UGT1A3 also involved at higher concentrations.
- Diclofenac significantly inhibited steviol glucuronidation in human liver microsomes (Ki = 4.2 μM).
Conclusions:
- UGT2B7 plays a key role in steviol glucuronidation.
- The interaction between steviol and diclofenac highlights the potential for botanical-drug interactions.
- Further in vivo studies are needed to confirm the clinical relevance of these interactions.
Keywords:
Botanical–drug interactionGlucuronidationHLMISInhibitionSVGSteviolUDP glucuronosyltransferaseUGTUGT2B7human liver microsomesinternal standardsteviol glucuronideMore Related Videos
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