Study on the Bioavailability of Proanthocyanidin A2 from Longan (Dimocarpus longan Lour.) Flower in Rat

Dimocarpus longan Lour., known as longan (dragon eye) in the Orient, belongs to the Sapindaceae family. Longan is a subtropical fruit widely grown in Taiwan, China and Southeast Asia. In traditional Chinese medicine the flowers are used for the treatment of leucorrhea and kidney disorders. The water extract of longan flower was found to possess high antioxidative activity against LDL oxidation in vitro. The major antioxidative compounds against LDL oxidation in longan flower were identified to be (-)-epicatechin and proanthocyanidin A2 (PA2). Intervention studies with procyanidin-rich extracts such as cocoa and wine suggest protective effects of proanthocyanidin against cardiovascular diseases. However, the bioavailiabily study of A-type proanthocyanidins is quite limited. The aim of this study was to evaluate the bioavailiabilty of PA2 following oral administration by Sprague-Dawley rats. After tube-feeding 250 mg/kg BW of PA2 for 2 hr, PA2 could not be detected in plasma. The pharmacokinetic parameter Cmax and T1/2 were 24.60±1.5 μg/mL and 8.46±0.8 min respectively after i.v. injection of 30 mg/kg BW PA2. The bioavailability of PA2 was almost 0. After tube-feeding 200 mg/kg BW of PA2 for 24 hr, 63% PA2 were excreted to feces. We used in vitro fermentation of PA2 with rat microbiota to examine the metabolites of PA2. The main metabolites of PA2 were 5-(3, 4-dihydroxyphenyl)-γ- valerolactone and 3-(3''-hydroxyphenyl) propionic acid (3-HPP). These metabolites of PA2 were also found in urine and intestine of rats tube-fed with 200 mg/kg BW PA2 indicating the possibility of absorption of PA2 after oral administration. After introducting PA2 (100 mg/kg BW) directly into the cecum for 6 hr, PA2 was found to be degraded into 21 phenolic acid compounds. The major metabolites were found to be 3-HPP, 3, 4-dihydroxyphenylpropionic acid and hippuric acid. Our results showed that intestinal microbiota could convert PA2 to a number of smaller phenolic compounds. The health potential of these metabolites should be further studied in order to understand the effect of PA2, since the PA2 concentrations in plasma and other tissues are very low.