Parichehr Hassanzadeh1,2, Elham Arbabi3, Fatemeh Atyabi4,5, Rassoul Dinarvand4,5. 1. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Pari_has@yahoo.com. 2. Neurological Research Center, Tehran University of Medical Sciences, Tehran, Iran. Pari_has@yahoo.com. 3. Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
RATIONALE: Resveratrol is a polyphenolic compound with antioxidant, anti-inflammatory, and neuroprotective effects. It has also shown antidepressant-like effects in the behavioral studies; however, its mechanism(s) of action merit further evaluation. OBJECTIVES: The interaction between the nerve growth factor (NGF) and endocannabinoid system (eCBs) and their contribution to the antidepressant or emotional activity prompted us to evaluate their implications in the mechanism of action of resveratrol. METHODS: After single and 4-week intraperitoneal (i.p.) once-daily injections of resveratrol (40, 80, and 100 mg/kg), amitriptyline (2.5, 5, and 10 mg/kg), or clonazepam (10, 20, and 40 mg/kg) into male Wistar rats, eCB and NGF contents were quantified in the brain regions implicated in the modulation of emotions by isotope-dilution liquid chromatography/mass spectrometry and Bio-Rad protein assay, respectively. In the case of any significant alteration of brain eCB or NGF level, the effect of pre-treatment with cannabinoid CB1 or CB2 receptor antagonist (AM251 or SR144528) was investigated. RESULTS: Four-week treatment with resveratrol or amitriptyline resulted in a significant and sustained enhancement of NGF and eCB contents in dose-dependent and brain region-specific manner. Neither acute nor 4-week treatment with clonazepam affected brain eCB or NGF contents. Pre-treatment with AM251 (3 mg/kg), but not SR144528, prevented the enhancement of NGF protein levels. AM251 exhibited no effect by itself. CONCLUSIONS: Resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB1 receptors.
RATIONALE: Resveratrol is a polyphenolic compound with antioxidant, anti-inflammatory, and neuroprotective effects. It has also shown antidepressant-like effects in the behavioral studies; however, its mechanism(s) of action merit further evaluation. OBJECTIVES: The interaction between the nerve growth factor (NGF) and endocannabinoid system (eCBs) and their contribution to the antidepressant or emotional activity prompted us to evaluate their implications in the mechanism of action of resveratrol. METHODS: After single and 4-week intraperitoneal (i.p.) once-daily injections of resveratrol (40, 80, and 100 mg/kg), amitriptyline (2.5, 5, and 10 mg/kg), or clonazepam (10, 20, and 40 mg/kg) into male Wistar rats, eCB and NGF contents were quantified in the brain regions implicated in the modulation of emotions by isotope-dilution liquid chromatography/mass spectrometry and Bio-Rad protein assay, respectively. In the case of any significant alteration of brain eCB or NGF level, the effect of pre-treatment with cannabinoid CB1 or CB2 receptor antagonist (AM251 or SR144528) was investigated. RESULTS: Four-week treatment with resveratrol or amitriptyline resulted in a significant and sustained enhancement of NGF and eCB contents in dose-dependent and brain region-specific manner. Neither acute nor 4-week treatment with clonazepam affected brain eCB or NGF contents. Pre-treatment with AM251 (3 mg/kg), but not SR144528, prevented the enhancement of NGF protein levels. AM251 exhibited no effect by itself. CONCLUSIONS:Resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB1 receptors.
Authors: Mounira Banasr; Gerald W Valentine; Xiao-Yuan Li; Shannon L Gourley; Jane R Taylor; Ronald S Duman Journal: Biol Psychiatry Date: 2007-06-21 Impact factor: 13.382
Authors: Iris Erlund; Raika Koli; Georg Alfthan; Jukka Marniemi; Pauli Puukka; Pirjo Mustonen; Pirjo Mattila; Antti Jula Journal: Am J Clin Nutr Date: 2008-02 Impact factor: 7.045
Authors: Stephanie R Wesolowski; Karim C El Kasmi; Karen R Jonscher; Jacob E Friedman Journal: Nat Rev Gastroenterol Hepatol Date: 2016-10-26 Impact factor: 46.802
Authors: Melissa A Ribeiro; Rafael P Aguiar; Franciele F Scarante; Eduardo J Fusse; Rubia M W de Oliveira; Francisco S Guimaraes; Alline C Campos Journal: Front Pharmacol Date: 2022-01-21 Impact factor: 5.810
Authors: Riccardo Vago; Francesco Fiorio; Francesco Trevisani; Andrea Salonia; Francesco Montorsi; Arianna Bettiga Journal: Nutrients Date: 2022-01-21 Impact factor: 5.717
Authors: Luciana Cristina B Fernandes; Ianara Mendonça Costa; Marco Aurelio M Freire; Francisca Overlânia V Lima; Francisca Idalina Neta; Eudes Euler de Souza Lucena; Rodrigo Dias Alves; Jose Rodolfo Lopes P Cavalcanti; Francisco Irochima Pinheiro; Eduardo Pereira de Azevedo; Carlos Iberê A Freitas; Fausto Pierdoná Guzen Journal: Curr Neuropharmacol Date: 2021 Impact factor: 7.363