Anukunwithaya Tosapol, Tantisira Mayuree H, Tantisira Boonyong, Khemawoot Phisit
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand.
Planta Med. 2017 May;83(8):710-717. doi: 10.1055/s-0042-122344. Epub 2016 Dec 19.
ECa 233, a standardized extract of , has been found to exhibit various positive neurological effects and to have a good safety profile. The present study aimed to explore the disposition kinetics of ECa 233, containing madecassoside (53.1 %) and asiaticoside (32.3 %), in rats. The extract was intravenously or orally administered at doses from 50 to 200 mg/kg. Plasma, tissues, urine, and feces were collected at time points from 0 to 48 h after dosing. The levels of madecassoside and asiaticoside, as well as their postulated triterpenic metabolites, madecassic acid and asiatic acid, in biological samples, were simultaneously measured by liquid chromatography-tandem mass spectrometry. The results showed that all animals had a good tolerability for ECa 233, whereas madecassic and asiatic acids were found in negligible amounts after pharmacokinetic assessment. Madecassoside and asiaticoside demonstrated rather similar absorption and tissue distribution profiles. They were rapidly absorbed, reaching maximum levels within 5-15 min after oral administration, but they had poor oral bioavailability, less than 1 %. Both triterpenoids were extensively distributed in the brain, stomach, and skin within 1 h and remained there for at least 4 h after dosing. Madecassoside and asiaticoside in ECa 233 were mainly excreted as an unchanged form after being injected, and exclusively as triterpenic acid metabolites in feces after oral administration. The pharmacokinetic results obtained could provide some guidance for an appropriate dosing regimen of ECa 233 in future studies. This study also provided the first evidence demonstrating the presence of madecassoside and asiaticoside in their target tissues.
ECa 233是[植物名称]的标准化提取物，已发现其具有多种积极的神经学效应且安全性良好。本研究旨在探讨含羟基积雪草苷（53.1%）和积雪草苷（32.3%）的ECa 233在大鼠体内的处置动力学。提取物以50至200mg/kg的剂量静脉注射或口服给药。给药后0至48小时的各个时间点采集血浆、组织、尿液和粪便。通过液相色谱 - 串联质谱法同时测定生物样品中羟基积雪草苷、积雪草苷及其假定的三萜代谢产物羟基积雪草酸和积雪草酸的水平。结果表明，所有动物对ECa 233均具有良好的耐受性，而在药代动力学评估后发现羟基积雪草酸和积雪草酸的含量极少。羟基积雪草苷和积雪草苷表现出相当相似的吸收和组织分布特征。它们吸收迅速，口服给药后5至15分钟内达到最高水平，但口服生物利用度较差，低于1%。两种三萜类化合物在1小时内广泛分布于脑、胃和皮肤中，给药后至少在这些组织中留存4小时。ECa 233中的羟基积雪草苷和积雪草苷静脉注射后主要以原形排泄，口服给药后则仅以三萜酸代谢产物的形式在粪便中排泄。所获得的药代动力学结果可为未来研究中ECa 233的合适给药方案提供一些指导。本研究还首次提供了证据，证明羟基积雪草苷和积雪草苷在其靶组织中的存在。
