Urinary metabolites of isorhynchophylline in rats and their neuroprotective activities in the HT22 cell assay

被引:23
作者
Chen, Fangfang [1 ]
Qi, Wen [1 ]
Sun, Jiahong [2 ]
Simpkins, James W. [2 ]
Yuan, Dan [1 ]
机构
[1] Shenyang Pharmaceut Univ, Dept Tradit Chinese Med, Shenyang 110016, Peoples R China
[2] W Virginia Univ, Ctr Basic & Translat Stroke Res, Dept Physiol & Pharmacol, Robert C Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA
基金
中国国家自然科学基金;
关键词
Uncaria hook; Isorhynchophylline; Metabolites from rat urine; Neuroprotection; HT22; cell; UNCARIA-RHYNCHOPHYLLA; INDOLE ALKALOIDS; OXIDATIVE STRESS; TOBACCO ALKALOIDS; IDENTIFICATION; GLUTAMATE; LEAVES; HOOKS; VINCAMINE; PRESSURE;
D O I
10.1016/j.fitote.2014.05.022
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Isorhynchophylline is one of the major alkaloids from the Uncaria hook possessing the effects of lowered blood pressure, vasodilatation and protection against ischemia-induced neuronal damage. However, the metabolic pathway of isorhynchophylline has not been fully reported yet. In this paper, the metabolism of isorhynchophylline was investigated in rats. Five metabolites were isolated by using solvent extraction and repeated chromatographic methods, and identified by spectroscopic methods including UV, MS, NMR and CD experiments. Three new compounds were identified as 5-oxoisorhynchophyllic acid-22-O-beta-D-glucuronide (M1), 17-O-demethyl-16,17-dihydro isorhynchophylline (M2) and 5-oxoisorhynchophyllic acid (M4) together with two known compounds isorhynchophylline (M0) and rhynchophylline (M3). Possible metabolic pathways of isorhynchophylline are proposed. Furthermore, the activity assay for all the metabolites showed that isorhynchophylline (M0) exhibited potent neuroprotective effects against glutamate-induced HT22 cell death. However, little or weak neuroprotective activities were observed for M1-M4. Our present study is important to further understand its metabolic fate and disposition in humans. (c) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:156 / 163
页数:8
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