Generic placeholder image

Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Research Article

A Proteomics Study of the Subacute Toxicity of Rat Brain after Long- Term Exposure of Gelsemium elegans

Author(s): Meng-Ting Zuo, Si-Juan Huang, Yong Wu, Mo-Huan Tang, Hui Yu, Xue-Jia Qi and Zhao-Ying Liu*

Volume 15, Issue 5, 2022

Published on: 15 February, 2022

Article ID: e091221198709 Pages: 8

DOI: 10.2174/1874467214666211209144139

Price: $65

conference banner
Abstract

Background: Gelsemium elegans (G. elegans) has been shown to have strong pharmacological and pharmacodynamic effects in relevant studies both in China and USA. G. elegans has been used as a traditional medicine to treat a variety of diseases and even has the potential to be an alternative to laboratory synthesized drugs. However, its toxicity severely limited its application and development. At present, there is little attention paid to protein changes in toxicity.

Aim: This study investigated the toxicity effects after long-term exposure of G. elegans of the rat brain through proteomic.

Methods: : 11 differential abundance proteins were detected, among which 8 proteins were higher in the G. elegans- exposure group than in the control group, including Ig-like domain-containing protein (N/A), receptor-type tyrosine-protein phosphatase C (Ptprc), disheveled segment polarity protein 3 (Dvl3), trafficking protein particle complex 12 (Trappc12), seizure-related 6 homologlike (Sez6l), transmembrane 9 superfamily member 4 (Tm9sf4), DENN domain-containing protein 5A (Dennd5a) and Tle4, whereas the other 3 proteins do the opposite including Golgi to ER traffic protein 4 (Get4), vacuolar protein sorting 4 homolog B (Vps4b) and cadherin-related 23 (CDH23). Furthermore, we performed validation of WB analysis on the key protein CDH23.

Results: Finally, only fewer proteins and related metabolic pathways were affected, indicating that there was no accumulative toxicity of G. elegans. G. elegans has the potential to develop and utilize of its pharmacological activity. CHD23, however, is a protein associated with hearing.

Conclusion: Whether the hearing impairment is a sequela after G. elegans exposure remains to be further studied.

Keywords: Gelsemium elegans, proteomics, toxicity, CDH23, hearing, western blot.

Graphical Abstract

[1]
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]
[2]
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]
[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] [PMID: 14522437]
[4]
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]
[5]
Xu, Y.K.; Liao, S.G.; Na, Z.; Hu, H.B.; Li, Y.; Luo, H.R. Gelsemium alkaloids, immunosuppressive agents from Gelsemium elegans. Fitoterapia, 2012, 83(6), 1120-1124.
[http://dx.doi.org/10.1016/j.fitote.2012.04.023] [PMID: 22579843]
[6]
Cai, J.; Lei, L.S.; Chi, D.B. Antineoplastic effect of koumine in mice bearing H22 solid tumor. Nan Fang Yi Ke Da Xue Xue Bao, 2009, 29(9), 1851-1852.
[PMID: 19778809]
[7]
Zhang, J.Y.; Wang, Y.X. Gelsemium analgesia and the spinal glycine receptor/allopregnanolone pathway. Fitoterapia, 2015, 100, 35-43.
[http://dx.doi.org/10.1016/j.fitote.2014.11.002] [PMID: 25447163]
[8]
Hoong, N.C.; Ying, C.; Sing Cn, Y.; Shan, T.C.; Qin, Y.Z.; Chun, L.Y.; Shui-Sheng, W.; Fei, Y.M. Application of mid-infared spectroscopy with multivariate analysis for the discrimination of toxic plant, Gelsemium elegans. Vib. Spectrosc., 2018, S092420311830050X.
[9]
Zhou, Z.; Wu, L.; Zhong, Y.; Fang, X.; Liu, Y.; Chen, H.; Zhang, W. Gelsemium elegans poisoning: a case with 8 months of follow-up and review of the literature. Front. Neurol., 2017, 8, 204.
[http://dx.doi.org/10.3389/fneur.2017.00204] [PMID: 28567028]
[10]
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]
[11]
Xiang, H.; Zhou, Y.J.; Huang, P.L.; Yu, C.N.; Liu, J.; Liu, L.Y.; He, P. Lethal poisoning with Gelsemium elegans in Guizhou, China. Public Health, 2016, 136, 185-187.
[http://dx.doi.org/10.1016/j.puhe.2016.02.031] [PMID: 27026250]
[12]
Zhang, Y.G.; Huang, G.Z. Poisoning by toxic plants in China. Report of 19 autopsy cases. Am. J. Forensic Med. Pathol., 1988, 9(4), 313-319.
[http://dx.doi.org/10.1097/00000433-198812000-00009] [PMID: 3239549]
[13]
Jin, G.L.; Su, Y.P.; Liu, M.; Xu, Y.; Yang, J.; Liao, K.J.; Yu, C.X. Medicinal plants of the genus Gelsemium (Gelsemiaceae, Gentianales)- a review of their phytochemistry, pharmacology, toxicology and traditional use. J. Ethnopharmacol., 2014, 152(1), 33-52.
[http://dx.doi.org/10.1016/j.jep.2014.01.003] [PMID: 24434844]
[14]
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]
[15]
Ma, T.Y.; Yu, T.F.; Li, S.M.; Li, G. [Advance in studies on Aconitum traditional Chinese medicines in toxicokinetics and metabonomics]. Zhongguo Zhongyao Zazhi, 2014, 39(11), 1972-1975. [Advance in studies on Aconitum traditional Chinese medicines in toxicokinetics and metabonomics].
[PMID: 25272824]
[16]
Liu, Y.M.; Hui, R.R.; He, C.C.; Duan, J.A.; Tang, Y.P.; Li, J.X. A metabonomic approach to a unique detoxification effect of co-use of Euphorbia kansui and Zizyphus jujuba. Phytother. Res., 2013, 27(11), 1621-1628.
[http://dx.doi.org/10.1002/ptr.4914] [PMID: 23280778]
[17]
Nicholson, J.K.; Lindon, J.C. Systems biology: Metabonomics. Nature, 2008, 455(7216), 1054-1056.
[http://dx.doi.org/10.1038/4551054a] [PMID: 18948945]
[18]
Tang, J.; Hu, W.; Chen, S.; Di, R.; Liu, Q.; Wang, X.; He, X.; Gan, S.; Zhang, X.; Zhang, J.; Chen, W.; Chu, M. The genetic mechanism of high prolificacy in small tail han sheep by comparative proteomics of ovaries in the follicular and luteal stages. J. Proteomics, 2019, 204, 103394.
[http://dx.doi.org/10.1016/j.jprot.2019.103394] [PMID: 31146049]
[19]
Chen, X.Q.; Jiang, J.; Wang, X.T.; Zhang, C.L.; Ji, A.Y.; Chen, X.J. Role and mechanism of Dvl3 in the esophageal squamous cell carcinoma. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(22), 7716-7725.
[http://dx.doi.org/10.26355/eurrev_201811_16393] [PMID: 30536315]
[20]
Scrivens, P.J.; Noueihed, B.; Shahrzad, N.; Hul, S.; Brunet, S.; Sacher, M. C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking. Mol. Biol. Cell, 2011, 22(12), 2083-2093.
[http://dx.doi.org/10.1091/mbc.e10-11-0873] [PMID: 21525244]
[21]
Milev, M.P.; Grout, M.E.; Saint-Dic, D.; Cheng, Y.H.H.; Glass, I.A.; Hale, C.J.; Hanna, D.S.; Dorschner, M.O.; Prematilake, K.; Shaag, A.; Elpeleg, O.; Sacher, M.; Doherty, D.; Edvardson, S. Mutations in TRAPPC12 manifest in progressive childhood encephalopathy and golgi dysfunction. Am. J. Hum. Genet., 2017, 101(2), 291-299.
[http://dx.doi.org/10.1016/j.ajhg.2017.07.006] [PMID: 28777934]
[22]
Miyazaki, T.; Hashimoto, K.; Uda, A.; Sakagami, H.; Nakamura, Y.; Saito, S.Y.; Nishi, M.; Kume, H.; Tohgo, A.; Kaneko, I.; Kondo, H.; Fukunaga, K.; Kano, M.; Watanabe, M.; Takeshima, H. Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family. FEBS Lett., 2006, 580(17), 4057-4064.
[http://dx.doi.org/10.1016/j.febslet.2006.06.043] [PMID: 16814779]
[23]
Kuhn, P.H.; Koroniak, K.; Hogl, S.; Colombo, A.; Zeitschel, U.; Willem, M.; Volbracht, C.; Schepers, U.; Imhof, A.; Hoffmeister, A.; Haass, C.; Roßner, S.; Bräse, S.; Lichtenthaler, S.F. Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons. EMBO J., 2012, 31(14), 3157-3168.
[http://dx.doi.org/10.1038/emboj.2012.173] [PMID: 22728825]
[24]
Dislich, B.; Wohlrab, F.; Bachhuber, T.; Müller, S.A.; Kuhn, P.H.; Hogl, S.; Meyer-Luehmann, M.; Lichtenthaler, S.F. Label-free Quantitative Proteomics of Mouse Cerebrospinal Fluid Detects β-Site APP Cleaving Enzyme (BACE1) protease substrates in vivo. Mol. Cell. Proteomics, 2015, 14(10), 2550-2563.
[http://dx.doi.org/10.1074/mcp.M114.041533] [PMID: 26139848]
[25]
Zhang, X.; Li, X.; Ning, F.; Shang, Y.; Hu, X. TLE4 acts as a corepressor of Hes1 to inhibit inflammatory responses in macrophages. Protein Cell, 2019, 10(4), 300-305.
[http://dx.doi.org/10.1007/s13238-018-0554-3] [PMID: 29869113]
[26]
Buscarlet, M.; Stifani, S. The ‘Marx’ of Groucho on development and disease. Trends Cell Biol., 2007, 17(7), 353-361.
[http://dx.doi.org/10.1016/j.tcb.2007.07.002] [PMID: 17643306]
[27]
Magnani, P.; Conforti, A.; Zanolin, E.; Marzotto, M.; Bellavite, P. Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice. Psychopharmacology (Berl.), 2010, 210(4), 533-545.
[http://dx.doi.org/10.1007/s00213-010-1855-2] [PMID: 20401745]
[28]
Lagziel, A.; Ahmed, Z.M.; Schultz, J.M.; Morell, R.J.; Belyantseva, I.A.; Friedman, T.B. Spatiotemporal pattern and isoforms of cadherin 23 in wild type and waltzer mice during inner ear hair cell development. Dev. Biol., 2005, 280(2), 295-306.
[http://dx.doi.org/10.1016/j.ydbio.2005.01.015] [PMID: 15882574]
[29]
Siemens, J.; Lillo, C.; Dumont, R.A.; Reynolds, A.; Williams, D.S.; Gillespie, P.G.; Müller, U. Cadherin 23 is a component of the tip link in hair-cell stereocilia. Nature, 2004, 428(6986), 950-955.
[http://dx.doi.org/10.1038/nature02483] [PMID: 15057245]
[30]
Pickles, J.O.; Comis, S.D.; Osborne, M.P. Cross-links between stereocilia in the guinea pig organ of Corti, and their possible relation to sensory transduction. Hear. Res., 1984, 15(2), 103-112.
[http://dx.doi.org/10.1016/0378-5955(84)90041-8] [PMID: 6436216]

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