Isolation of Luteolin and Luteolin-7-O-glucoside from Dendranthema morifolium Ramat Tzvel and Their Pharmacokinetics in Rats

Luteolin and luteolin-7-O-glucoside were isolated from the ethanolic extract of Dendranthema morifolium Ramat Tzvel. The structures of these analytes were identified by nuclear magnetic resonance H-1 and C-13 NMR) and mass spectrometry. Ethanolic and water extracts contained luteolin-7-O-glucoside at 4.19 and 6.56%, respectively. However, the level of luteolin was only 0.19% in the ethanolic extract, and luteolin was not detected in the water extract. To examine the pharmacokinetics and bioavailability of luteolin and luteolin-7-O-glucoside in rats, parallel studies of luteolin (10 mg/kg, iv; and 100 mg/kg, po) and luteolin-7-O-glucoside (10 mg/kg, iv; and 1 g/kg, po) were conducted. The analytes were detected by high-performance liquid chromatography coupled with a photodiode array detector. A phenyl-hexyl (150 x 4.6 mm iv; 5.0 mu m) column was used to separate the analytes from the biological samples. The pharmacokinetic data demonstrate that the areas under the concentration curves (AUCs) of luteolin were 261 +/- 33 and 611 +/- 89 (mu g/mL) after luteolin administration (10 mg/kg, iv; and 100 mg/kg, po, respectively). The oral bioavailability of luteolin was 26 +/- 6%. The AUCs of luteolin-7-O-glucoside were 229 +/- 15 and 2109 +/- 350 (min mu g/mL) after administration of luteolin-7-O-glucoside (10 mg/kg, iv; and 1 g/kg, po, respectively). The oral bioavailability of luteolin-7-O-glucoside was approximately 10 +/- 2%. In the group that received luteolin-7-O-glucoside orally, a biotransformed luteolin product was detected, but this product was not detected in the group that received luteolin-7-O-glucoside intravenously. The biotransformation ratio of luteolin to luteolin-7-O-glucoside (the AUC ratio of metabolite/parent compound) was approximately 48.78 +/- 0.12%. These results demonstrate that luteolin-7-O-glucoside is primarily hydrolyzed to luteolin in the gastrointestinal tract and then absorbed into the systemic circulation.