Login Register Cart 0
Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Comparative Analysis of the Gelsemium Alkaloids Metabolism in Human, Pig, Goat, and Rat Liver Microsomes

Author(s): Yi-Rong Wang, Meng-Ting Zuo, Wen-Bo Xu and Zhao-Ying Liu*

Volume 25, Issue 2, 2024

Published on: 02 April, 2024

Page: [157 - 163] Pages: 7

DOI: 10.2174/0113892002298633240322071126

Price: $65

conference banner
Abstract

Aim: The aim of this study was to investigate the metabolism of Gelsemium elegans in human, pig, goat and rat liver microsomes and to elucidate the metabolic pathways and cleavage patterns of the Gelsemium alkaloids among different species.

Methods: A human, goat, pig and rat liver microsomes were incubated in vitro. After incubating at 37°C for 1 hour and centrifuging, the processed samples were detected by HPLC/Qq-TOFMS was used to detect alcohol extract of Gelsemium elegans and its metabolites.

Results: Forty-six natural products were characterized from alcohol extract of Gelsemium elegans and 13 metabolites were identified. These 13 metabolites belong to the gelsemine, koumine, gelsedine, humantenine, yohimbane, and sarpagine classes of alkaloids. The metabolic pathways included oxidation, demethylation and dehydrogenation. After preliminary identification, the metabolites detected in the four species were different. All 13 metabolites were detected in pig and rat microsomes, but no oxidative metabolites of Gelsedine-type alkaloids were detected in goat and human microsomes.

Conclusion: In this study, Gelsemium elegans metabolic patterns in different species are clarified and the in vitro metabolism of Gelsemium elegans is investigated. It is of great significance for its clinical development and rational application.

« Previous Next »
Graphical Abstract

[1]
Dutt, V.; Dhar, V.J.; Sharma, A. Antianxiety activity of Gelsemium sempervirens. Pharm. Biol., 2010, 48(10), 1091-1096.
[http://dx.doi.org/10.3109/13880200903490521] [PMID: 20860436]
[2]
Lin, H.; Qiu, H.; Cheng, Y.; Liu, M.; Chen, M.; Que, Y.; Que, W. Gelsemium elegans benth: Chemical components, pharmacological effects, and toxicity mechanisms. Molecules, 2021, 26(23), 7145.
[http://dx.doi.org/10.3390/molecules26237145] [PMID: 34885727]
[3]
Rujjanawate, C.; Kanjanapothi, D.; Panthong, A. Pharmacological effect and toxicity of alkaloids from Gelsemium elegans Benth. J. Ethnopharmacol., 2003, 89(1), 91-95.
[http://dx.doi.org/10.1016/S0378-8741(03)00267-8]
[4]
Xu, Y.K.; Yang, L.; Liao, S.G.; Cao, P.; Wu, B.; Hu, H.B.; Guo, J.; Zhang, P. Koumine, humantenine, and yohimbane alkaloids from Gelsemium elegans. J. Nat. Prod., 2015, 78(7), 1511-1517.
[http://dx.doi.org/10.1021/np5009619] [PMID: 26103517]
[5]
Huang, C.Y.; Yang, K.; Cao, J.J.; Wang, Z.Y.; Wu, Y.; Sun, Z.L.; Liu, Z.Y. Integration of metabolomics and transcriptomicsto comprehensively evaluate the metabolic effects of Gelsemium elegans on pigs. Animals, 2021, 11(5), 1192.
[http://dx.doi.org/10.3390/ani11051192] [PMID: 33919302]
[6]
Wang, Q.; Wang, D.; Zuo, Z.; Ye, B.; Dong, Z.; Zou, J. Effects of dietary koumine on growth performance, intestinal morphology, microbiota, and intestinal transcriptional responses of Cyprinus carpio. Int. J. Mol. Sci., 2022, 23(19), 11860.
[http://dx.doi.org/10.3390/ijms231911860] [PMID: 36233179]
[7]
Wang, L.; Chen, S.; Gao, X.; Liang, X.; Lv, W.; Zhang, D.; Jin, X. Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genus gelsemium : A comprehensive review. J. Enzyme Inhib. Med. Chem., 2023, 38(1), 2155639.
[http://dx.doi.org/10.1080/14756366.2022.2155639] [PMID: 36629436]
[8]
Xu, Y.; Qiu, H.Q.; Liu, H.; Liu, M.; Huang, Z.Y.; Yang, J.; Su, Y.P.; Yu, C.X. Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone. Pharmacol. Biochem. Behav., 2012, 101(3), 504-514.
[http://dx.doi.org/10.1016/j.pbb.2012.02.009] [PMID: 22366214]
[9]
Sun, H.; Zhang, A.; Wang, X. Potential role of metabolomic approaches for Chinese medicine syndromes and herbal medicine. Phytother. Res., 2012, 26(10), 1466-1471.
[http://dx.doi.org/10.1002/ptr.4613] [PMID: 22422429]
[10]
XU, Y.; Zheng, M.; Li, SP Pharmacokinetics and tissue distribution of koumine in rats. J. Fuji. Med. Uni., 2013, 47(4), 199-203.
[11]
Zhang, S.; Hu, S.; Yang, X.; Shen, J.; Zheng, X.; Huang, K.; Xiang, Z. Development of a liquid chromatography with mass spectrometry method for the determination of gelsemine in rat plasma and tissue: Application to a pharmacokinetic and tissue distribution study. J. Sep. Sci., 2015, 38(6), 936-942.
[http://dx.doi.org/10.1002/jssc.201401168] [PMID: 25580713]
[12]
Zuo, M.T.; Wang, Z.Y.; Yang, K.; Li, Y.J.; Huang, C.Y.; Liu, Y.C.; Yu, H.; Zhao, X.J.; Liu, Z.Y. Characterization of absorbed and produced constituents in goat plasma urine and faeces from the herbal medicine Gelsemium elegans by using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. J. Ethnopharmacol., 2020, 252, 112617.
[http://dx.doi.org/10.1016/j.jep.2020.112617] [PMID: 31988014]
[13]
Huang, S.J.; Zuo, M.T.; Qi, X.J.; Ma, X.; Wang, Z.Y.; Liu, Z.Y. In vitro metabolism of humantenine in liver microsomes from human, pig, goat and rat. Curr. Drug Metab., 2021, 22(10), 795-7801.
[http://dx.doi.org/10.2174/1389200222666210901113530] [PMID: 34468296]
[14]
Yu, H.; Xiao, S.; Huang, YJ. Characterization of gelsemine metabolites in pig liver S9. J. Trad. Chin. Veter. Med., 2019, 38(2), 5-8.
[15]
Xiao, S.; Huang, Y-J.; Liu, Y-C. In vitro metabolism of koumine in pig. Chin. J. Vet. Sci., 2018, 38(8), 1568-1572.
[16]
Shoaib, R.M.; Zhang, J.Y.; Mao, X.F.; Wang, Y.X. Gelsemine and koumine, principal active ingredients of Gelsemium, exhibit mechanical antiallodynia via spinal glycine receptor activation-induced allopregnanolone biosynthesis. Biochem. Pharmacol., 2019, 161, 136-148.
[http://dx.doi.org/10.1016/j.bcp.2019.01.014] [PMID: 30668937]
[17]
Sun, R.; Chen, M.; Hu, Y.; Lan, Y.; Gan, L.; You, G.; Yue, M.; Wang, H.; Xia, B.; Zhao, J.; Tang, L.; Cai, Z.; Liu, Z.; Ye, L. CYP3A4/5 mediates the metabolic detoxification of humantenmine, a highly toxic alkaloid from Gelsemium elegans Benth. J. Appl. Toxicol., 2019, 39(9), 1283-1292.
[http://dx.doi.org/10.1002/jat.3813] [PMID: 31119768]
[18]
Yang, S.; Liu, Y.; Sun, F.; Zhang, J.; Jin, Y.; Li, Y.; Zhou, J.; Li, Y.; Zhu, K. Gelsedine-type alkaloids: Discovery of natural neurotoxins presented in toxic honey. J. Hazard. Mater., 2020, 381, 120999.
[http://dx.doi.org/10.1016/j.jhazmat.2019.120999] [PMID: 31430640]
[19]
Li, X.X.; Wang, Y.; Zheng, Q.C.; Zhang, H.X. Detoxification of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by cytochrome P450 enzymes: A theoretical investigation. J. Inorg. Biochem., 2016, 154, 21-28.
[http://dx.doi.org/10.1016/j.jinorgbio.2015.10.009] [PMID: 26544505]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy