以大鼠模式探討龍眼花 proanthocyanidin A2 的生物可利用性

Abstract

龍眼 (Dimocarpus longan) 屬於無患子科，龍眼屬植物，廣泛生長於臺灣、中國及東南亞等地區，在民間藥學上用以治療白帶、腎臟病等。本研究室先前研究指出龍眼花水萃物具有良好之體外抗 LDL 氧化活性，其主要活性成分為 (-)-epicatechin 及 proanthocyanidin A2 (PA2)。然而，目前 A-type 原花青素於生物體內生物可利用率之研究仍相當缺乏，故本研究之目的係以大鼠模式評估 PA2 之生物可利用率。以胃管餵食大鼠 200 mg/kg BW PA2 後，以斷尾採血方式收集血液，經 HPLC 分析後在血液中無法測得 PA2；以股靜脈注射給予大鼠 30 mg/kg BW PA2，測得 Cmax 為 24.60 ± 1.5 μg/mL，T1/2 為 8.46 ± 0.8 min；經計算後得 PA2 之口服生物可利用率為 0。當進行組織分佈探討時，各臟器中皆無法測得 PA2，其大多存在於腸胃道中，並隨著時間排出體外，胃管餵食後 8-12 hr 為 PA2 最大排除期，24小時後約 63% 自糞便排出體外。由體外腸道微生物發酵試驗結果可知 5-(3,4-dihydroxyphenyl)-γ-valerolactone 及3-hydroxyphenylpropionic acid (3-HPP) 為 PA2 之主要代謝產物，而在管餵大鼠 200mg/kg BW PA2 之腸道及尿液中亦可測得此代謝物。盲腸結紮試驗中測得 21 種腸道微生物代謝產物，其中以3-HPP、3,4-Dihydroxyphenylpropionic acid 及hippuric acid 為主。綜合以上試驗結果可知 PA2 在血液及組織中的濃度很低，但可藉由腸道微生物作用代謝成多種小分子的酚類化合物，此類代謝產物與 PA2 生理活性之相關性需進一步加以探討以了解 PA2 生理活性之作用機制。

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.