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Molecules 2017, 22(4), 565; doi:10.3390/molecules22040565

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

1
College of Chinese Medicinal Materials, Jilin Agriculture University, Xincheng Street 2888th, Changchun 130118, Jilin, China
2
Institute of Translational Medicine, the First Hospital of Jilin University, Xinmin Street 71th, Changchun 130021, Jilin, China
3
Center of Ophthalmology, the Second Hospital of Jilin University, Ziqiang Street 218th, Changchun 130041, Jilin, China
*
Author to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 20 February 2017 / Revised: 27 March 2017 / Accepted: 27 March 2017 / Published: 31 March 2017
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Abstract

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. View Full-Text
Keywords: ergosterol; ergosteryl 2-naphthoate; antidepressant; forced swim test ergosterol; ergosteryl 2-naphthoate; antidepressant; forced swim test
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MDPI and ACS Style

Lin, M.; Li, H.; Zhao, Y.; Cai, E.; Zhu, H.; Gao, Y.; Liu, S.; Yang, H.; Zhang, L.; Tang, G.; Wang, R. Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems. Molecules 2017, 22, 565.

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