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Planta Med 2015; 81(01): 46-55
DOI: 10.1055/s-0034-1383357
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Isolation and Identification of Twelve Metabolites of Isocorynoxeine in Rat Urine and their Neuroprotective Activities in HT22 Cell Assay

Wen Qi
1   Department of Traditional Chinese Medicines, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Fangfang Chen
1   Department of Traditional Chinese Medicines, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Jiahong Sun
2   Center for Basic and Translational Stroke Research, Department of Physiology and Pharmacology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, United States
,
James W. Simpkins
2   Center for Basic and Translational Stroke Research, Department of Physiology and Pharmacology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, United States
,
Dan Yuan
1   Department of Traditional Chinese Medicines, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
› Author Affiliations
Further Information

Publication History

received 14 March 2014
revised 12 October 2014

accepted 17 October 2014

Publication Date:
17 December 2014 (online)

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Abstract

Isocorynoxeine, one of the major alkaloids from Uncaria Hook, shows the effects of lowering blood pressure, vasodilatation, and protection against ischemia-induced neuronal damage. In this paper, the metabolism of isocorynoxeine was investigated in rats. Twelve metabolites and the parent drug were isolated by using solvent extraction and repeated chromatographic methods, and determined by spectroscopic methods including UV, MS, NMR, and CD experiments. Seven new compounds were identified as 11-hydroxyisocorynoxeine, 5-oxoisocorynoxeinic acid-22-O-β-D-glucuronide, 10-hydroxyisocorynoxeine, 17-O-demethyl-16,17-dihydro-5-oxoisocorynoxeine, 5-oxoisocorynoxeinic acid, 21-hydroxy-5-oxoisocorynoxeine, and oxireno[18, 19]-5-oxoisocorynoxeine, together with six known compounds identified as isocorynoxeine, 18,19-dehydrocorynoxinic acid, 18,19-dehydrocorynoxinic acid B, corynoxeine, isocorynoxeine-N-oxide, and corynoxeine-N-oxide. Possible metabolic pathways of isocorynoxeine are proposed. Furthermore, the activity assay for the parent drug and some of its metabolites showed that isocorynoxeine exhibited a significant neuroprotective effect against glutamate-induced HT22 cell death at the maximum concentration. However, little or weak neuroprotective activities were observed for M-3, M-6, M-7, and M-10. Our present study is important to further understand their metabolic fate and disposition in humans.

Key words

Uncaria Hook - Rubiaceae - isocorynoxeine - metabolites from rat urine - neuroprotective activities - HT22 cell

Supporting Information

 

  • References

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