Moduratory effect of Thai traditional medicine (Yahom Tultavai) on hepatic cytochrome P450 enzymes and pentobarbital-induced sleeping in mice

Abstract

Yahom Tultavai is a Thai traditional medicine that has been widely used for the treatment of nausea, vomiting, dizziness and weakness in aged-people, especially. Its formula contains several medicinal plants, and one of them is Kaempferia galanga L., which has ethyl-p-methoxycinnamate (EPMC) as its major compound. Recently, several herbs and traditional medicines have been reported to demonstrate herbal-drug interaction with conventional medicines. This study aims to investigate the effect of Yahom Tultavai extracts on hepatic cytochrome P450 enzymes and pentobarbital-induced sleeping in mice. Three extracts of Yahom Tultavai, using dichloromethane, methanol and distilled water as solvents were orally administered for 28 days prior to determine CYP1A1, CYP1A2, CYP2B, CYP2E1 and CYP3A4 activities. All three extracts significantly inhibited CYP1A1, CYP1A2 and CYP 2E1 activities, but only dichloromethane extract enhanced CYP2B activity. In addition, all three extracts had no effect on CYP3A4 activity. As an indicator for metabolic drug interaction, pentobarbital-induced sleeping time was decreased in connection with the induction of CYP2B activity between 7 and 28 days of dichloromethane extract and EPMC-treated animals when compared to control. In conclusion, Yahom Tultavai extracts affected hepatic microsomal CYP enzyme activities and reduced pentobarbital-induced sleeping time in mice. The results suggest that Yahom Tultavai may potentially cause herbal and conventional drug interaction, which can affect the clinical implication of drug action. Therefore, the co-administration of Yahom Tultavai with certain drugs should be carefully considered.

Keywords: Thai traditional medicine; Yahom Tultavai; cytochrome P450; herbal-drug interaction; pentobarbital-induced sleeping.

Figure 1

HPLC chromatograms of standard ethyl-p-methoxycinnamate (EPMC) and three Yahom Tultavai extracts: (A) EPMC, (B) dichloromethane extract, (C) methanol extract , using mobile phase A containing acetronitrile: methanol: 20mM NaH₂PO₄ (30:40:30) and detection at 270 nm; (D) aqueous extract using mobile phase B containing 25uM ammonium phosphate buffer pH 7.5: methanol (95:5) and detection at 250 nm.

Figure 2

Effect of Ethyl-p-methoxycinnamate (EPMC) and dichloromethane extract of Yahom Tultavai on sleeping time in phentobarbital-induced mice. Values are expressed as mean±S.E, the numbers of animals used is specified in Table 3. ^a,b,c represents significant differences to control, EPMC and dichloromethane extract of Yahom Tultavai treated groups at the same duration, respectively at p < 0.05

Fig 3

Effects of Ethyl-p-methoxycinnamate (EPMC) and dichloromethane extract of Yahom Tultavai on CYP2B activity in phentobarbital-induced mice. Results are expressed as mean ± S.E., (n=3). ^a,b,c represents significant differences to control, EPMC and dichloromethane extract of Yahom Tultavai treated groups at the same duration, respectively at p < 0.05.