Citation: Yue Cong, Jing-Gong Guo, Zhi Tang, Qing-Chun Zhang, Zong-Wei Cai. Identification of in vitro and in vivo metabolites of 12β-hydroxylveratroylzygadenine associated with neurotoxicity by using HPLC-MS/MS[J]. Chinese Chemical Letters, ;2014, 25(8): 1107-1111. doi: 10.1016/j.cclet.2014.05.016 shu

Identification of in vitro and in vivo metabolites of 12β-hydroxylveratroylzygadenine associated with neurotoxicity by using HPLC-MS/MS

1.
a Institute of Pharmacy, Pharmaceutical College, Henan University, Jinming Road, Kaifeng 475004, China;
2.
b State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China;
3.
c The Key Laboratory of Plant Stress Biology, Henan University, Jinming Road, Kaifeng 475004, China

Received Date: 11 February 2014
Available Online: 21 March 2014
Fund Project: This work was supported by the National Natural Science Foundation of China (No. 21102035). (No. 21102035)

Metabolism study was carried out on 12β-hydroxylveratroylzygadenine (VOG) that is a cevine-type alkaloid existing in Veratrum nigrum L. and a neurotoxic component. In order to better understand the potential mechanism of neurotoxicity of VOG, this study measured VOG-induced DNA damage in the cerebellum and cerebral cortex of mice after 7 days repetitive oral dose by using single-cell gel electrophoresis (Comet assay). High performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and applied to separate and identify in vitro and in vivo metabolites of VOG for investing the possible relationship of metabolism and neurotoxicity. In vitro experiment was carried out using rat liver microsomes, while the in vivo study was conducted on rats. The obtained results indicated that VOG might cause DNA damage in cerebellum and cerebral cortex of mice in a dosedependent manner. Hydrolysis of ester bond and O-demethylation were proposed to be themain in vivo metabolic pathways of VOG, while the major in vitro metabolic pathways were proposed as methyl oxidation to aldehyde, dehydrogenation, hydrolysis of ester bond, hydrolysis of ester bond together with acetylation, and methoxylation. O-Demethylation reaction was likely to be associated with reactive oxygen species production, leading to the DNA damage.
- 12β-Hydroxylveratroylzygadenine,
- Metabolites,
- O-Demethylation,
- LC-MS
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