In silico, in vitro and in vivo studies indicate resveratrol analogue as a potential alternative for neuroinflammatory disorders.

Autor: de Assis PM; NUPICS, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil., Fávero A; NUPICS, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil., Menegasso JF; Laboratory of Autoimmunity and Immunopharmacology (LAIF), Federal University of Santa Catarina, 88906-072 Araranguá, Santa Catarina, Brazil., Meinel RS; Chemistry Department, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil., Marion GM; Graduate Program in Computational Modeling, Department of Computer Science, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil., Nunes VSP; Graduate Program in Computational Modeling, Department of Computer Science, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil., Goliatt PVZC; Graduate Program in Computational Modeling, Department of Computer Science, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil., da Silva AD; Chemistry Department, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil., Dutra RC; Laboratory of Autoimmunity and Immunopharmacology (LAIF), Federal University of Santa Catarina, 88906-072 Araranguá, Santa Catarina, Brazil., Raposo NRB; NUPICS, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil. Electronic address: nadiacritt@gmail.com.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2020 May 15; Vol. 249, pp. 117538. Date of Electronic Publication: 2020 Mar 10.
DOI: 10.1016/j.lfs.2020.117538
Abstrakt: Inflammaging is known as an imbalance between pro-inflammatory and anti-inflammatory immune mechanisms, being related to the onset of neurological disorders, such as major depression and Alzheimer's disease. Considering the known disadvantages regarding the FDA approved drug to manage such illnesses, resveratrol emerges as a natural drug candidate, despite its low bioavailability. In this study, resveratrol analogues were evaluated for their capacity of inhibiting acetylcholinesterase in silico, in vitro, and in vivo. Molecular docking simulations pointed out RSVA1 and RSVA6 as potent inhibitors, even more than resveratrol. Ellman's assay demonstrated RSVA6 as capable of inhibiting 92.4% of the enzyme activity. Further, male Swiss mice were pretreated with RSVA6 (100 mg kg -1 ) 60 min before receiving scopolamine (1 mg kg -1 ). The Novel Recognition Object (NOR), Object Location (OLT), and Buried Pellet tests (BPL) demonstrated an RSVA6 neuroprotective effect. In the second round of tests, mice received a single intraperitoneal injection of lipopolysaccharide (0.5 mg kg -1 ) 24 h before treatment with RSVA6 (1, 10, and 100 mg kg -1 ). The Open Field (OFT), Tail Suspension (TST), and Splash tests (ST) were evaluated. LPS had no significant effect on the crossing and rearing number, indicating an association between the immobility time and anhedonia observed in the TST and ST, respectively, with depressive-like behavior. RSVA6 significantly reduced the depressive-like behavior triggered by LPS in the TST and ST. Altogether, our data suggest RSVA6 as a potential drug candidate for the treatment of neuroinflammatory conditions.
Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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