Influence of Dietary Macronutrients on Induction of Hepatic Drug Metabolizing Enzymes by Coleus forskohlii Extract in Mice

Abstract

Summary From studies in mice, we have reported that Coleus forskohlii extract (CFE), a popular herbal weight-loss ingredient, markedly induced hepatic drug metabolizing enzymes, especially cytochrome P450 (CYP), and interacted with co-administered drugs. This study was designed to examine how the induction of drug metabolizing enzymes by CFE was influenced by different levels of macronutrients in the diet. Mice were fed a non-purified diet or semi-purified diet with and without CFE (0.3-0.5%) for 14-18 d, and changes in the ratio of liver weight to body weight, an indicator of hepatic CYP induction, and hepatic drug metabolizing enzymes were analyzed. The ratio of liver weight to body weight, content and activities of CYPs, and activity of glutathione S-transferase were higher in a semi-purified standard diet (AIN93G formula) group than in high sucrose (62.9%) and high fat (29.9%) diet groups. Different levels of protein (7%, 20%, and 33%) in the diets did not influence CFE-induced CYP induction or increase the ratio of liver weight to body weight. The effect of CFE on the ratio of liver weight to body weight was higher with a semi-purified diet than with a non-purified diet, and was similar between dietary administration and intragastric gavage when the CFE dose and the diet were the same. There was a positive correlation between CFE-induced CYP induction and the content of starch in the diets, suggesting that dietary starch potentiates CFE-induced CYP induction in mice. The mechanism of enhanced CYP induction remains unclear.

The Major Cytochrome P450 Subtype Activities in Diet-Induced Non- Alcoholic Steatohepatitis Mouse Model

“…Our laboratory previously reported that CYP, especially CYP3A, activity was induced more in mice fed a low protein diet (7% (w/w) casein) than in mice fed a control diet (20% (w/w) casein) [20][21][22]. A high-fat diet (P:F:C = 20:60:20) did not cause any changes in the hepatic expression of CYP3A, whereas regular chow (P:F:C = 26:13:61) increased CYP3A11 mRNA and CYP3A protein expression levels in the livers of mice more than the control diet (P:F:C = 20:10:70) [23].…”

Identification of Compounds in <i>Coleus forskohlii</i> Extract Involved in the Induction of Hepatic CYP and Fatty Liver in Mice

“…Previous studies revealed that the induction of hepatic CYP and fatty liver by CFE in vivo can be easily evaluated by an increase in the liver/body weight ratio 16 . Therefore, the ability of target components in the materials to cause CYP and fatty liver was confirmed by dietary administration to mice and evaluation of increases in the liver/body weight ratio.…”

“…The supernatant was centrifuged at 105,000 g at 4 for 60 min and used as microsomes to determine the total CYP content and CYP activities. The total CYP content was determined as previously described 16 . The activities of various CYP enzymes were determined using the P450-Glo TM CYP1A1 System Luciferin-CEE assay, CYP1A2 System Luciferin-1A2 assay, CYP2C9 System Luciferin-H assay, CYP3A4 System Luciferin PPXE assay and the NADPH Regeneration System, according to the manufacturer s instructions Promega .…”

Effects of forskolin and rolipram on serum leptin, resistin and adiponectin levels in diet induced obesity in Wistar rats

“…Indeed, forskolin is a very effective activator of ACs 1 to 8 but not of AC9 [20,21]. CF has been reported to prove of value in the clinic for prevention of cancer metastasis [22].…”