<i>Coleus forskohlii</i> Extract Attenuates the Hypoglycemic Effect of Tolbutamide <i>in vivo via</i> 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, CY-P2C, 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.

Potential Application of Some Lamiaceae Species in the Management of Diabetes

“…The leaves of Coleus have been reported to have a wide range of pharmaceutical applications, including in diabetes and weight loss [ 34 ]. The extract of Coleus has been reported to attenuate/reduce the hypoglycaemic action of tolbutamide via a hepatic CYP2C-mediated mechanism [ 38 ]. Forskolin, the main predominant constituent of C .…”

Comparison of CYP Induction by <i>Coleus forskohlii</i> Extract and Recovery in the Small Intestine and Liver of Mice

“…The components were 5.6% water, 0.3% protein, 22.7% lipids, 2.2% ash, and 69.2% carbohydrates. The HPLC chromatographic profile of CFE has been reported elsewhere, 26) and the analyzed contents of forskolin and 1,9-dideoxyforskolin in the CFE sample were 10.37 and 1.71%, respectively. All other reagents were purchased from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan).…”

“…However, the possibility of CFE-drug interactions by the mechanism of hepatic CYP induction exists, as shown in the case of warfarin and tolbutamide. 26,27) In the small intestine, high concentrations of CFE components are present after oral administration. On the other hand, those concentrations in the liver are likely lower due to the processes of absorption, distribution and metabolism.…”

“…25) In addition, we have shown that CFE interacts with warfarin and tolbutamide via induction of hepatic CYP, resulting in decreased drug ef-ficacy in mouse in vivo studies. 26,27) Furthermore, while forskolin was not involved in the CYP induction, 25) many other compounds are likely involved. However, the contribution of CFE administration to CYP induction in the small intestine remains unclear.…”