在大鼠体内口服巴戟天根提取物后莫诺托品和去乙酰asperulosidic 酸的药代动力学和组织分布。
Pharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in rats.
机构信息
School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1 Qiuyang Road, Shangjie Town, Minhou County, Fuzhou, 350122, People's Republic of China.
School of Pharmacy, Zhejiang University of Traditional Chinese Medicine, Gaoke Road, Fuyang District, Hangzhou, 310053, People's Republic of China.
出版信息
BMC Complement Altern Med. 2018 Oct 24;18(1):288. doi: 10.1186/s12906-018-2351-1.
BACKGROUND
Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO.
METHODS
An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods.
RESULTS
Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC, C and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus.
CONCLUSION
The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.
背景
包括莫诺苷（MON）和去乙酰asperulosidic 酸（DA）在内的环烯醚萜苷（IGs）是桑科植物桑白皮（MO）根的主要化学成分，具有多种药理活性，包括抗骨质疏松、抗炎和抗风湿作用。本研究旨在通过研究 MO 中环烯醚萜苷的药代动力学和组织分布，进一步阐明 MO 的药理作用。
方法
建立并验证了一种超高效液相色谱-串联质谱（UHPLC-MS）法，用于同时测定 Wistar 大鼠血浆和各种组织中 MON 和 DA 的浓度。采用甲醇直接沉淀法从大鼠血浆和组织样品中提取 MON、DA 和对乙酰氨基酚（ACE）作为内标（IS）。大鼠灌胃给予 1650mg/kg MO 和 25、50 和 100mg/kg MO 环烯醚萜苷（MOIG），或静脉注射 MOIG 25mg/kg 进行 MON 和 DA 的药代动力学研究。此外，口服给予 100mg/kg MOIG 进行 MON 和 DA 的组织分布研究。构建非房室药代动力学模型。根据验证的方法计算组织分布。
结果
雌雄大鼠的药代动力学参数存在显著差异。雌鼠 MON 和 DA 的 AUC、C 和生物利用度均高于雄鼠。MON 和 DA 口服后主要分布在肠道和胃，值得注意的是，MON 和 DA 在大鼠下丘脑的浓度较高。
结论
本研究结果可能为 MOIGs 在体内的生物学行为提供新的认识，有助于解释其药理作用，并为从 MO 根提取的这些 IGs 的合理临床应用提供实验线索。
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