The CB1 Receptor-Mediated Endocannabinoid Signaling and NGF: The Novel Targets of Curcumin

Abstract

Increasing interest has recently been attracted towards the identification of natural compounds including those with antidepressant properties. Curcumin has shown promising antidepressant effect, however, its molecular target(s) have not been well defined. Based on the interaction between the neurotrophins and endocannabinoid system as well as their contribution to the emotional reactivity and antidepressant action, here we show that 4-week treatment with curcumin, similar to the classical antidepressant amitriptyline, results in the sustained elevation of brain nerve growth factor (NGF) and endocannabinoids in dose-dependent and brain region-specific fashion. Pretreatment with cannabinoid CB1 receptor neutral antagonist AM4113, but not the CB2 antagonist SR144528, prevents the enhancement of brain NGF contents. AM4113 exerts no effect by itself. Our findings by presenting the CB1 receptor-mediated endocannabinoid signaling and NGF as novel targets for curcumin, suggest that more attention should be focused on the therapeutic potential of herbal medicines including curcumin.

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Acknowledgments

This work was supported by a grant from Shahid Beheshti University of Medical Sciences (SB587). The authors thank Ali Mahdavi, PhD, Department of immunology, Tarbiat Modarres University, Tehran, for technical assistance; and Nosrat Naderi, MD, FACG, Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, for helpful comments on the manuscript.

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Correspondence to Parichehr Hassanzadeh.

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Supplementary Figure 1: Brain regional levels of NGF are not altered following single injection of 100 mg kg−1 curcumin or 5 mg kg−1 amitriptyline. (A) NGF levels 24 h after the treatment, (B) NGF levels 48 h after the treatment, (C) NGF levels 72 h after the treatment. Data are expressed as mean ± SEM of n=6/group. Vehicles 1 and 2 are related to curcumin and amitriptyline, respectively. (TIFF 15 kb)

Supplementary Figure 2: Acute administration of 150 mg kg−1 curcumin or 10 mg kg−1 amitriptyline does not alter brain NGF levels. (A) NGF levels 24 h after the treatment, (B) NGF levels 48 h after the treatment, (C) NGF levels 72 h after the treatment. Data are expressed as mean ± SEM of n=6/group. (TIFF 15 kb)

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Hassanzadeh, P., Hassanzadeh, A. The CB1 Receptor-Mediated Endocannabinoid Signaling and NGF: The Novel Targets of Curcumin. Neurochem Res 37, 1112–1120 (2012). https://doi.org/10.1007/s11064-012-0716-2

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Keywords

  • Curcumin
  • Amitriptyline
  • Endocannabinoid system
  • CB1 receptors
  • CB2 receptors
  • NGF
  • Brain
  • Rat