Hua-Hai Zhang1,2, Ya-Jun Huang3, Yan-Chun Liu3, Xu-Yan Jiang4, Shuo-Xin Zhang1,2, Zhao-Ying Liu3,5. 1. College of Forestry, Northwest A&F University, 3 Taicheng Rd., Yangling, Shaanxi, 712100, China. 2. Qinling National Forest Ecosystem Research Station, Huoditang, Ningshan, Shaanxi, 711600, China. 3. College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China. 4. College of Landscape Architecture and Arts, Northwest A&F University, 3 Taicheng Rd., Yangling, Shaanxi, 712100, China. 5. Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha, Hunan, 410128, China.
Abstract
RATIONALE: Gelsemium elegans Benth. belongs to the family Loganiaceae and is widely distributed in northern America, east Asia, and southeast Asia. It has attracted wide attention for its diverse biological effects and complex architectures. Gelsevirine is one of the major components in G. elegans. Compared with other alkaloids from G. elegans, gelsevirine exhibits equally potent anxiolytic effects but with less toxicity. However, the metabolism of gelsevirine has not been clearly elucidated. METHODS: The metabolism of gelsevirine was investigated using liver S9 fractions derived from rat liver homogenates by centrifugation at 9000 g. A rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS) method was applied to characterize the gelsevirine metabolites. RESULTS: We discovered a total number of four metabolites of gelsevirine. The metabolic pathways of gelsevirine consisted of hydrogenation, N-demethylenation and oxidation in rat liver S9. CONCLUSIONS: This is the first study on the metabolism of gelsevirine. We proposed possible metabolic pathways of gelsevirine. These findings may warrant future studies of the in vivo metabolism of gelsemine in animals.
RATIONALE: Gelsemium elegans Benth. belongs to the family Loganiaceae and is widely distributed in northern America, east Asia, and southeast Asia. It has attracted wide attention for its diverse biological effects and complex architectures. Gelsevirine is one of the major components in G. elegans. Compared with other alkaloids from G. elegans, gelsevirine exhibits equally potent anxiolytic effects but with less toxicity. However, the metabolism of gelsevirine has not been clearly elucidated. METHODS: The metabolism of gelsevirine was investigated using liver S9 fractions derived from rat liver homogenates by centrifugation at 9000 g. A rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS) method was applied to characterize the gelsevirine metabolites. RESULTS: We discovered a total number of four metabolites of gelsevirine. The metabolic pathways of gelsevirine consisted of hydrogenation, N-demethylenation and oxidation in rat liver S9. CONCLUSIONS: This is the first study on the metabolism of gelsevirine. We proposed possible metabolic pathways of gelsevirine. These findings may warrant future studies of the in vivo metabolism of gelsemine in animals.