9416 The Oral Bioavailability of Luteolin and Apigenin in Chrysanthemum Morifolium Extract Is Much Higher Than When They are Given As Pure Individual Compounds in Rats

Zhongjian Chen , Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University, Hangzhou, China
Hao Pan , Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University, Hangzhou, China
Liping Li , Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University, Hangzhou, China
Chen Ting , Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University, Hangzhou, China
Ruwei Wang , Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, China
Su Zeng , Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University, Hangzhou, China
Huidi Jiang , Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University, Hangzhou, China
Flavonoids are vital bioactive components in Chrysanthemum morifolium extract (CME), and luteolin-7-O-b-D-glucoside and apigenin-7-O-b-D-glucoside are the major flavonoids in CME. Luteolin-7-O-b-D-glucoside and apigenin-7-O-b-D-glucoside are absorbed as their aglycones, luteolin and apigenin, when CME is given orally. The pharmacokinetics of luteolin and apigenin after oral administration of CME has been investigated in our lab. However, there is no data about the absolute bioavailability of these two aglycones. The objective of the present study was to compare the difference in the absolute bioavailability of luteolin and apigenin between oral administration of CME and pure luteolin or apigenin. A total of 5 groups of rats (5 rats in each group) were administrated 6.5 mg/kg of luteolin (iv, ig), 5.4 mg/kg of apigenin (iv, ig), and 100 mg/kg of CME(equal to 6.5 mg/kg of luteolin and 5.4 mg/kg of apigenin), respectively. The plasma concentrations of luteolin and apigenin were analyzed with a HPLC method developed in our lab. The area under the curve (AUC) for luteolin and apigenin was calculated using Winnolin pharmacokinetic software. The following results were obtained: 1) The AUC of luteolin and apigenin following intravenous injection of pure luteolin and apigenin were 14.7±2.3 and 84.5±16.7 mg/L*h, respectively; 2) The AUC of apigenin following oral administration of pure apigenin was 6.5±3.1 mg/L*h, whereas the AUC of luteolin following oral administration of pure luteolin could not be calculated, due to the low concentrations of luteolin detected; 3) The AUC of luteolin and apigenin was 8.2±4.3 and 70.4±25.0 mg/L*h, respectively, after CME was orally given. Therefore, the absolute bioavailability of apigenin after dosage with pure apigenin or with CME was 7.7% and 83.3%, respectively, while the bioavailability of luteolin after dosage with CME was 55.4%. The current study suggests that the absolute bioavailability of luteolin and apigenin in CME is much higher than their bioavailability when given as pure individual compounds. The other compounds that are present with luteolin and apigenin in CME might influence the absorption or metabolism of luteolin and apigenin in vivo when CME was orally given. (The project was supported by Zhejiang Administration of Chinese Traditional Medicine,China, 2007ZA012 )