Home » Key Scientific Articles » Urinary metabolites of isorhynchophylline in rats and their neuroprotective activities in the HT22 cell assay.

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

Chen F1, Qi W1, Sun J2, Simpkins JW2, Yuan D3. Fitoterapia. 2014 ;97:156-63.

1Department of Traditional Chinese Medicines, Shenyang Pharmaceutical University, Shenyang, China.and

2Center for Basic and Translational Stroke Research, Department of Physiology and Pharmacology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, United States.and

3Department of Traditional Chinese Medicines, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: [email protected]

Abstract

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 potentneuroprotective 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.

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