Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
BMC Complement Altern Med. 2019 Sep 2;19(1):235. doi: 10.1186/s12906-019-2653-y.
Oxyresveratrol is a major bioactive component derived from the heartwood of Artocarpus lacucha. This compound exerts several biological activities, including neuroprotective effects in vitro and in vivo. However, there is limited pharmacokinetic information on this compound, especially its distribution in neuronal tissue and its route of excretion. The aim of this study was to investigate the pharmacokinetic profiles of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats.
Male Wistar rats were administered with oxyresveratrol 10 mg/kg, oxyresveratrol 10 mg/kg plus piperine 1 mg/kg via intravenous or oxyresveratrol 100 mg/kg, oxyresveratrol 100 mg/kg plus piperine 10 mg/kg via oral gavage. Plasma, internal organs, urine, and feces were collected. Determination of the oxyresveratrol concentration in biological samples was performed by liquid chromatography tandem mass spectrometry.
The combination with piperine had shown a significantly higher maximum concentration in plasma approximately 1500 μg/L within 1-2 h after oral dosing, and could increase oral bioavailability of oxyresveratrol approximately 2-fold. Oxyresveratrol could widely distributed most of the internal organs with a tissue to plasma ratio of 10-100 fold within 5 min after dosing. Urinary excretion of oxyresveratrol glucuronide was the major route of excretion after administration of oxyresveratrol alone and in combination with piperine.
The addition of piperine could enhance some of the pharmacokinetic properties of oxyresveratrol via both intravenous and oral administration. This pharmacokinetic information will be useful for appropriate strategies to develop oxyresveratrol as a phytopharmaceutical product.
氧代白藜芦醇是从 Artocarpus lacucha 的心材中提取的主要生物活性成分。该化合物具有多种生物学活性，包括体外和体内的神经保护作用。然而，关于该化合物的药代动力学信息有限，特别是其在神经元组织中的分布及其排泄途径。本研究旨在研究氧代白藜芦醇单独给药和与生物增强剂胡椒碱联合给药在大鼠体内的药代动力学特征。
雄性 Wistar 大鼠静脉注射或口服给予氧代白藜芦醇 10mg/kg，氧代白藜芦醇 10mg/kg 加胡椒碱 1mg/kg，或氧代白藜芦醇 100mg/kg，氧代白藜芦醇 100mg/kg 加胡椒碱 10mg/kg。采集血浆、内脏器官、尿液和粪便。采用液相色谱-串联质谱法测定生物样品中氧代白藜芦醇的浓度。
与胡椒碱合用可使口服给药后 1-2 小时内的血浆中最大浓度（约 1500μg/L）显著升高，可使氧代白藜芦醇的口服生物利用度提高约 2 倍。氧代白藜芦醇在给药后 5 分钟内可广泛分布于大多数内脏器官，组织与血浆的比值为 10-100 倍。单独给予氧代白藜芦醇和与胡椒碱合用后，氧代白藜芦醇葡萄糖醛酸苷的尿排泄是主要的排泄途径。
胡椒碱的加入可通过静脉和口服给药增强氧代白藜芦醇的部分药代动力学特性。这些药代动力学信息将有助于制定适当的策略，将氧代白藜芦醇开发为植物药产品。
