In silico, in vitro and in vivo studies indicate resveratrol analogue as a potential alternative for neuroinflammatory disorders
| Autor: | Vinicius Schmitz Nunes, Amanda Fávero, Jaíne Ferrareis Menegasso, Adilson David da Silva, Priscila Vanessa Zabala Capriles Goliatt, Raissa Soares Meinel, Rafael C. Dutra, Gabriel Macedo Marion, Pollyana Mendonça de Assis, Nádia Rezende Barbosa Raposo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Lipopolysaccharide medicine.medical_treatment Intraperitoneal injection Scopolamine Anti-Inflammatory Agents Pharmacology Resveratrol In Vitro Techniques 030226 pharmacology & pharmacy Neuroprotection General Biochemistry Genetics and Molecular Biology Open field 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine In vivo Medicine Animals Computer Simulation General Pharmacology Toxicology and Pharmaceutics Inflammation business.industry General Medicine Acetylcholinesterase In vitro Molecular Docking Simulation 030104 developmental biology Neuroprotective Agents chemistry Nervous System Diseases business |
| Zdroj: | Life sciences. 249 |
| ISSN: | 1879-0631 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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