title: Implication of NGF and endocannabinoid signaling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential.
abstract: BACKGROUND
  Sesamol, a natural compound with anti-inflammatory, antioxidant and neuroprotective properties, has shown promising antidepressant-like effects. However, its molecular target(s) have not been well defined, which merits further investigation.
  
  
  OBJECTIVE
  Based on the interaction between the neurotrophin and endocannabinoid (eCB) systems and their contribution to emotional reactivity and antidepressant action, we aimed to investigate the involvement of nerve growth factor (NGF) and eCB signalling in the mechanism of action of sesamol.
  
  
  METHODS
  Following acute and 4-week intraperitoneal (i.p.) administration of sesamol (40, 80 and 100 mg/kg), the classical antidepressant amitriptyline (2.5, 5 and 10 mg/kg) or the benzodiazepine flurazepam (5, 10 and 20 mg/kg), brain regional levels of NGF and eCB contents were quantified in rats by Bio-Rad protein assay and isotope-dilution liquid chromatography/mass spectrometry, respectively. In the case of any significant change, the cannabinoid CB1 and CB2 receptor antagonists (AM251 and SR144528) were administered i.p. 30 min prior to the injection of sesamol, amitriptyline or flurazepam.
  
  
  RESULTS
  Following the chronic treatment, sesamol, similar to amitriptyline, resulted in the sustained elevation of NGF and eCB contents in dose-dependent and brain region-specific fashion. Neither acute nor chronic treatment with flurazepam altered brain NGF or eCB contents. Pretreatment with 3 mg/kg AM251, but not SR144528, prevented the elevation of NGF protein levels. AM251 exerted no effect by itself.
  
  
  CONCLUSIONS
  Sesamol, similar to amitriptyline, is able to affect brain NGF and eCB signalling under the regulatory drive of the CB1 receptors.
authors.affiliation: Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Evin, P.O. Box: 19835-187, Tehran, Iran, Pari_has@yahoo.com.
authors.forename: Parichehr
authors.initials: P
authors.lastname: Hassanzadeh
authors.forename: Anna
authors.initials: A
authors.lastname: Hassanzadeh
mesh_terms: D000639:Amitriptyline / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001892:Camphanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism*; D005479:Flurazepam / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D058990:Molecular Targeted Therapy; D020932:Nerve Growth Factor / Q000378:metabolism*; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000975:Antioxidants; D052117:Benzodioxoles; D001892:Camphanes; D063388:Endocannabinoids; D010636:Phenols; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D000639:Amitriptyline; C103505:AM 251; D020932:Nerve Growth Factor; C025583:sesamol; D005479:Flurazepam