Pharmacokinetic study of luteolin, apigenin, chrysoeriol and diosmetin after oral administration of Flos Chrysanthemi extract in rats

Abstract

Flos Chrysanthemi (the flower of Chrysanthemum morifolium Ramat.) is widely used in China as a food and traditional Chinese medicine for many diseases. Luteolin and apigenin are two main bioactive components in Flos Chrysanthemi, and chrysoeriol and diosmetin are two methylated metabolites of luteolin in vivo by cathechol-O-methyltransferase (COMT). However, there was lack of pharmacokinetic information of chrysoeriol and diosmetin after oral administration of Flos Chrysanthemi extract (FCE). The present study aimed to develop an HPLC-UV method for simultaneous determination of rat plasma concentration of luteolin, apigenin, chrysoeriol and diosmetin and utilize it in pharmacokinetic study of the four compounds after orally giving FCE to rats. The method was successfully validated and applied to the pharmacokinetic study when oral administration of FCE to rats with or without co-giving a COMT inhibitor, entacapone. Chrysoeriol and diosmetin were detected in rat plasma after oral administration of FCE and their concentrations were significantly decreased after co-giving entacapone. Furthermore, AUC of luteolin was significantly increased by entacapone, while that of chrysoeriol was decreased by entacapone, which revealed COMT might play an important role in the disposition of luteolin in rats after dosing of FCE. In conclusion, a sensitive, accurate and reproducible HPLC-UV method for simultaneous determination of luteolin, apigenin, chrysoeriol and diosmetin in rat plasma were developed, pharmacokinetics of chrysoeriol and diosmetin combined with luteolin and apigenin were characterized after oral administration of FCE to rats, which gave us more information on pharmacokinetics and potential pharmacological effects of FCE in vivo.

Graphical abstract

Fig. 1

Chemical structures of luteolin, apigenin, chrysoeriol, diosmetin and quercetin.

Fig. 2

HPLC chromatograms of luteolin, apigenin, chrysoeriol and diosmetin in rat plasma. A: blank plasma; B: plasma spiked with 0.025 μg/ml of luteolin (2), apigenin (3), chrysoeriol (4), diosmetin (5) and 0.500 μg/ml quercetin (1); C: plasma sample 30 min after oral administration of 100 mg/kg FCE to rats. All samples above were treated with hydrolysis.

Fig. 3

Mean-plasma concentration–time profiles of luteolin, apigenin, chrysoeriol and diosmetin after oral administration of 100 mg/kg FCE with or without co-giving 20 mg/kg entacapone to rats. Data were expressed as mean ± S.E.M, n = 5. Compared with the entacapone + CME group,*: P < 0.05, **: P < 0.01.