Chronic Silymarin, Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats

Abstract

Polyphenols have beneficial neurological effects delaying cognitive and motor decline in aging due to their antioxidant, antiinflammatory and neuroprotective properties. These effects could be related to SIRT1 activation (implicated in synaptic plasticity, memory and inflammation) and monoaminergic synthesis modulation. In this work, we studied in old male rats, the in vivo effects of long-term administration of different polyphenols (silymarin, quercetin and naringenin; 20 mg/kg/day i.p, 4 weeks) (Sprague-Dawley, 18 months) on cognition and motor coordination. We also analyzed in different brain regions: tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities, which mediate central monoaminergic neurotransmitters synthesis; and immunoreactivities of SIRT1 and NF-κB (total and acetylated forms). Results indicated that chronic polyphenolic treatments showed restorative effects on cognition and motor coordination consistently with the biochemical and molecular results. Polyphenols reversed the age-induced deficits in monoaminergic neurotransmitters (serotonin, noradrenaline, and dopamine), increasing TPH and TH activity. In addition, polyphenolic treatments increased SIRT1 levels and decreased NF-κB levels in hippocampus. These results confirm polyphenolic treatments as a valuable potential therapeutic strategy for attenuating inflamm-aging and brain function decline.

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Acknowledgements

Authors thank the financial contribution of: Universitat de les Illes Balears (UIB)-Govern Balear (ECT 025 09), Pont La Caixa-UIB Program (7/2014) and MINECO, Madrid, Spain (SAF2014-55903-R). F. Sarubbo was supported by a UIB predoctoral contract and MR Ramis was supported by a predoctoral FPU Spanish Ministry of Education fellowship.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the Bioethical Committee of the University of the Balearic Islands and with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Directive 86/609/EEC).

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Sarubbo, F., Ramis, M.R., Kienzer, C. et al. Chronic Silymarin, Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats. J Neuroimmune Pharmacol 13, 24–38 (2018). https://doi.org/10.1007/s11481-017-9759-0

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Keywords

  • Aging
  • Cognition
  • Polyphenols
  • Monoamine synthesis
  • SIRT1
  • NF-κb