title: Coleus forskohlii extract attenuates the hypoglycemic effect of tolbutamide in vivo via a hepatic cytochrome P450-mediated mechanism.
abstract: This in vivo study in rats evaluated whether Coleus forskohlii extract (CFE) taken orally interacted with tolbutamide, a hypoglycemic drug metabolized by CYP2C enzymes. Rats were fed 0%, 0.3%, 1% (w/w) CFE diet for 2 weeks, followed by 0% CFE diet for 1 day. They were then given 40 mg/kg tolbutamide by intragastric gavage. Blood glucose level was determined up to 6 h after tolbutamide administration. CFE treatment increased total CYP content and various CYP subtypes in the liver. In particular, increases in activity and protein expression were noted for the CYP2B, CYP2C, and CYP3A subtypes. CFE treatment dose-dependently attenuated both the hypoglycemic action of tolbutamide at 6 h and the plasma concentration of tolbutamide. The activity of (S)-warfarin 7-hydroxylase, a CYP2C enzyme was negatively correlated with plasma tolbutamide level, which also showed a negative correlation with the reduction of blood glucose level. These results indicate that CFE induced hepatic CYPs in rats and attenuated the hypoglycemic action of tolbutamide via a hepatic CYP2C-mediated mechanism.
authors.affiliation: Information Center, National Institute of Health and Nutrition.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yokotani
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sato
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
mesh_terms: D000818:Animals; D031330:Coleus; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D041743:Herb-Drug Interactions; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009108:Mumps Vaccine; D010936:Plant Extracts / Q000009:adverse effects* / Q000494:pharmacology*; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D009108:Mumps Vaccine; D010936:Plant Extracts; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide