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Implication of NGF and endocannabinoid signaling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential

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Abstract

Rationale

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.

Objectives

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.

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Acknowledgments

This work was supported by a grant (Sh-596) from Shahid Beheshti University of Medical Sciences. The authors thank Ali Mahdavi, Department of Immunology, Tarbiat Modarres University, Tehran, for technical assistance.

Conflict of interest

The authors declare that, except the income received from Shahid Beheshti University of Medical Sciences, no financial support or compensation has been received from any individual or corporate entity. There are no personal financial holdings that could be perceived as consulting a potential conflict of interest.

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Authors and Affiliations

  1. Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Evin, P.O. Box: 19835-187, Tehran, Iran

    Parichehr Hassanzadeh

  2. Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Parichehr Hassanzadeh

  3. Department of Molecular Biology, Faculty of Molecular and Cellular Sciences, Azad University, Parand, Iran

    Anna Hassanzadeh

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  1. Parichehr Hassanzadeh
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Correspondence to Parichehr Hassanzadeh.

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Hassanzadeh, P., Hassanzadeh, A. Implication of NGF and endocannabinoid signaling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential. Psychopharmacology 229, 571–578 (2013). https://doi.org/10.1007/s00213-013-3111-z

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  • DOI: https://doi.org/10.1007/s00213-013-3111-z

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