| 英文摘要
| Tricin (4′,5,7-trihydroxy-3′,5′-dimethoxyflavone) has demonstrated diverse biological activities like antioxidative, antiviral, anti-inflammatory, antihistamic, and cytofoxic activities. However, its oral availability is low. To improve its bioavailability, tricin 7-monophosphate as prodrug was synthesized and its bioavailability was investigated by comparison of IV and oral administrations in Wistar male rats. The result indicated that tricin 7-monophosphate (7-TMP), detected as tricin in blood, exhibited better bioavailability (21.8 %) than the parent compound. 7-TMP is found labile in whole blood where it is completely converted to tricin in 1 hour at 37oC.
Two maximum absorption peaks, detected in blood, were observed after oral administration (100, 300 and 700 mg/kg). This phenomenon implies the reabsorption of tricin through enterohepatic circulation and intestinal absorption.
The metabolic profile of this prodrug via intragastrical oral administration in rat was investigated. Five metabolites were characterized in rat urine by high performance liquid chromatography–solid phase extraction–tube transfer–NMR (LC-SPE-NMR). These metabolites were glucuronide conjugates of the parent compound tricin 5, 7-glcUA, 5-glcUA, 7-glcUA, and 4′-glcUA.
This study demonstrates tricin monophosphate (7-TMP) as prodrug to enhance the bioavailability of tricin is feasible. Via oral administration of 7-TMP at a dose of 100 mg/kg in rat, the blood tricin concentration could reach at least its IC50 (1 μM) against tumor cell lines over a period of 5.5 hours, relatively longer that that of iv injection (ca. 2h, 100 mg/kg). |
