Abstract
Kaempferia parviflora (KP) extract has recently attracted attention in Japan as a dietary supplement; however, there is little information regarding food-drug interactions (FDIs). The current study was conducted to clarify the FDI of KP extract via inhibition of cytochrome P450 3A (CYP3A), a typical drug-metabolizing enzyme. The inhibitory effects of KP extract and its main ingredients, 5,7-dimethoxyflavone (5,7-DMF) and 3,5,7,3’,4’-pentamethoxyflavone (3,5,7,3’,4’-PMF), on CYP3A-mediated midazolam 1’-hydroxylation (MDZ 1’-OH) activity were investigated in human liver microsomes. In addition, the effect of a single oral treatment with KP extract (135 mg/kg) on oral MDZ (15 mg/kg) metabolism was investigated in rats. Serum MDZ concentration was analyzed and pharmacokinetic parameters were compared with the control group. KP extract competitively inhibited MDZ 1’-OH activity with an inhibition constant value of 78.14 µg/ml, which was lower than the estimated concentration in the small intestine after ingestion. Furthermore, KP extract, 5,7-DMF, and 3,5,7,3’,4’-PMF inhibited the activity in a time-, NADPH-, and concentration-dependent manner. In vivo study showed that administration of KP extract to rats 2 h before MDZ significantly increased the area under the serum concentration-time curve and the maximum concentration of MDZ significantly by 2.3- and 1.9- fold, respectively (p < 0.05). Conversely, administration of MDZ 18 h after KP extract treatment displayed a weaker effect. These results suggest that KP extract competitively inhibits CYP3A-mediated MDZ metabolism, and that this inhibition may be time-dependent but not irreversible. This work suggests an FDI through CYP3A inhibition by KP extract.
Highlights
Dietary supplements are widely used to maintain and improve health and beauty
5,7-DMF (0.03-30 μM) and 3,5,7,3’,4’-PMF (0.02-20 μM), which are the main polymethoxyflavones in Kaempferia parviflora (KP) extract, did not inhibit MDZ 1’-OH activity even at the high concentrations used in this experiment (Fig. 2B, 2C)
We investigated whether KP extract and its main ingredients, 5,7-DMF and 3,5,7,3’,4’-PMF, cause food-drug interactions (FDIs) mediated by cytochrome P450 3A (CYP3A) inhibition
Summary
Products using herbal extracts are classified as foods in Japan, but some products, such as St. John’s wort, saw palmetto, and echinacea, are used as drugs in European countries[1–3]). In Japan, approval review regulations for herbal medicinal products were announced in 2007, and red vine leaf extract and chest berry extract have been approved as direct over-the-counter (OTC) medicines. Since these OTC drugs and supplements derived from herbal extracts are available at drug stores and online retailers, the number of people using them has been increasing
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