Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Planta Med. 2013 May;79(8):646-53. doi: 10.1055/s-0032-1328543. Epub 2013 May 14.
The xanthones α-mangostin and γ-mangostin are the major bioactive compounds in Garcinia mangostana (mangosteen) fruit extracts. Previously, we reported the pharmacokinetic properties of α-mangostin in rats. The purpose of this follow-up study was to compare the pharmacokinetic characteristics of α-mangostin and γ-mangostin in rats if administered as either a pure compound or as a component of a mangosteen fruit extract. The absolute bioavailability of γ-mangostin when administered as a pure compound was determined by giving male Sprague Dawley rats 2 mg/kg γ-mangostin intravenously or 20 mg/kg orally. A 160 mg/kg aliquot of mangosteen fruit extract was administered, containing α- and γ-mangostin doses equal to 20 mg/kg and 4.5 mg/kg of each pure compound, respectively. Plasma samples were collected for both pharmacokinetic studies, and compound concentrations were measured by LC-MS/MS. The pharmacokinetic of γ-mangostin after intravenous administration followed a two-compartment body model. The half-life of the distribution phase was 2.40 min, and that of the elimination phase was 1.52 h. After oral administration, both α- and γ-mangostin underwent intensive first-pass metabolism, and both compounds were conjugated rapidly after oral administration. When given as an extract, the total absorption of α- and γ-mangostin was not increased, but the conjugation was slower, resulting in increased free (unconjugated) compound exposure when compared to pure compound administration. Since reported beneficial biological activities of mangosteen xanthones are based on the free, unconjugated compounds, food supplements containing mangosteen fruit extracts should be preferred over the administration of pure xanthones.
藤黄酚 α-和 γ-是藤黄果（山竹）果实提取物中的主要生物活性化合物。此前，我们报道了 α-在大鼠体内的药代动力学特性。本后续研究的目的是比较以纯化合物或作为藤黄果提取物成分给药时 α-和 γ-在大鼠体内的药代动力学特征。雄性 Sprague Dawley 大鼠静脉给予 2 mg/kg γ-或口服给予 20 mg/kg γ-时，测定 γ-作为纯化合物给药时的绝对生物利用度。给予 160 mg/kg 藤黄果提取物，其中 α-和 γ-的剂量分别相当于 20 mg/kg 和 4.5 mg/kg 的纯化合物。对两种药代动力学研究均采集了血浆样本，并通过 LC-MS/MS 测定了化合物浓度。静脉给予 γ-后，药代动力学呈二室模型。分布相半衰期为 2.40 min，消除相半衰期为 1.52 h。口服给药后，α-和 γ-均经历强烈的首过代谢，且两者在口服给药后均迅速结合。当作为提取物给予时，α-和 γ-的总吸收并未增加，但结合较慢，与纯化合物给药相比，游离（未结合）化合物暴露增加。由于报道的藤黄果黄烷酮的有益生物学活性是基于游离的、未结合的化合物，因此含有藤黄果提取物的膳食补充剂应优于纯黄烷酮的给药。
