Cargando…

Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems

Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushro...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Mingzhu, Li, Haijun, Zhao, Yan, Cai, Enbo, Zhu, Hongyan, Gao, Yugang, Liu, Shuangli, Yang, He, Zhang, Lianxue, Tang, Guosheng, Wang, Ruiqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154707/
https://www.ncbi.nlm.nih.gov/pubmed/28362353
http://dx.doi.org/10.3390/molecules22040565
_version_ 1783357746420121600
author Lin, Mingzhu
Li, Haijun
Zhao, Yan
Cai, Enbo
Zhu, Hongyan
Gao, Yugang
Liu, Shuangli
Yang, He
Zhang, Lianxue
Tang, Guosheng
Wang, Ruiqing
author_facet Lin, Mingzhu
Li, Haijun
Zhao, Yan
Cai, Enbo
Zhu, Hongyan
Gao, Yugang
Liu, Shuangli
Yang, He
Zhang, Lianxue
Tang, Guosheng
Wang, Ruiqing
author_sort Lin, Mingzhu
collection PubMed
description Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid), 1-Ethylethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) in dichloromethane. Their chemical structures were defined by IR and NMR. The present study was also undertaken to investigate the antidepressant-like effects of Er and its derivatives in male adult mice models of depression, and their probable involvement of GABAergic and glutamatergic systems by the forced swim test (FST). The results indicated that Er and its derivatives display antidepressant effects. Moreover, one derivative of Er, ergosteryl 2-naphthoate (ErN), exhibited stronger antidepressant activity in vivo compared to Er. Acute administration of ErN (5 mg/kg, i.p.) and a combination of ErN (0.5 mg/kg, i.p.), reboxetine (2.5 mg/kg, i.p.), and tianeptine (15 mg/kg, i.p.) reduced the immobility time in the FST. Pretreatment with bicuculline (a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.) and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg/kg, i.p.) effectively reversed the antidepressant-like effect of ErN (5 mg/kg, i.p.). However, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p.) did not eliminate the reduced immobility time. Altogether, these results indicated that ErN produced antidepressant-like activity, which might be mediated by GABAergic and glutamatergic systems.
format Online
Article
Text
id pubmed-6154707
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61547072018-11-13 Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems Lin, Mingzhu Li, Haijun Zhao, Yan Cai, Enbo Zhu, Hongyan Gao, Yugang Liu, Shuangli Yang, He Zhang, Lianxue Tang, Guosheng Wang, Ruiqing Molecules Article Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid), 1-Ethylethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) in dichloromethane. Their chemical structures were defined by IR and NMR. The present study was also undertaken to investigate the antidepressant-like effects of Er and its derivatives in male adult mice models of depression, and their probable involvement of GABAergic and glutamatergic systems by the forced swim test (FST). The results indicated that Er and its derivatives display antidepressant effects. Moreover, one derivative of Er, ergosteryl 2-naphthoate (ErN), exhibited stronger antidepressant activity in vivo compared to Er. Acute administration of ErN (5 mg/kg, i.p.) and a combination of ErN (0.5 mg/kg, i.p.), reboxetine (2.5 mg/kg, i.p.), and tianeptine (15 mg/kg, i.p.) reduced the immobility time in the FST. Pretreatment with bicuculline (a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.) and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg/kg, i.p.) effectively reversed the antidepressant-like effect of ErN (5 mg/kg, i.p.). However, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p.) did not eliminate the reduced immobility time. Altogether, these results indicated that ErN produced antidepressant-like activity, which might be mediated by GABAergic and glutamatergic systems. MDPI 2017-03-31 /pmc/articles/PMC6154707/ /pubmed/28362353 http://dx.doi.org/10.3390/molecules22040565 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Mingzhu
Li, Haijun
Zhao, Yan
Cai, Enbo
Zhu, Hongyan
Gao, Yugang
Liu, Shuangli
Yang, He
Zhang, Lianxue
Tang, Guosheng
Wang, Ruiqing
Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems
title Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems
title_full Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems
title_fullStr Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems
title_full_unstemmed Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems
title_short Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems
title_sort ergosteryl 2-naphthoate, an ergosterol derivative, exhibits antidepressant effects mediated by the modification of gabaergic and glutamatergic systems
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154707/
https://www.ncbi.nlm.nih.gov/pubmed/28362353
http://dx.doi.org/10.3390/molecules22040565
work_keys_str_mv AT linmingzhu ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT lihaijun ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT zhaoyan ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT caienbo ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT zhuhongyan ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT gaoyugang ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT liushuangli ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT yanghe ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT zhanglianxue ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT tangguosheng ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems
AT wangruiqing ergosteryl2naphthoateanergosterolderivativeexhibitsantidepressanteffectsmediatedbythemodificationofgabaergicandglutamatergicsystems