The CB1 Receptor-Mediated Endocannabinoid Signaling and NGF: The Novel Targets of Curcumin
- 271 Downloads
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.
KeywordsCurcumin Amitriptyline Endocannabinoid system CB1 receptors CB2 receptors NGF Brain Rat
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.
Conflict of interest
- 32.Li Yu-Cheng, Wang Fu-Meng, Pan Ying, Qiang Li-Qin, Cheng Guang, Zhang Wei-Yun et al (2009) Antidepressant-like effects of curcumin on serotonergic receptor-coupled AC-cAMP pathway in chronic unpredictable mild stress of rats. Prog Neuropsychopharmacol Biol Psychiatry 33(3):435–449PubMedCrossRefGoogle Scholar
- 36.Abalo R, Cabezos PA, Vera G, Fernandez-pujol R, Martin MI (2010). The cannabinoid antagonist SR144528 enhances the acute effect of WIN 55,212-2 on gastrointestinal motility in the rat. Neurogastroenterol Motil 22(6): 694–e206Google Scholar
- 39.Paxinos G, Watson C (1997) The Rat Brain in Stereotaxic Coordinates. Academic Press, San DiegoGoogle Scholar
- 41.Hellweg R, Hock C, Hartung HD (1989) An improved rapid and highly sensitive enzyme immunoassay for nerve growth factor. Technique J Meth Cell Mol Biol 1:43–49Google Scholar
- 48.Hassanzadeh P, Hassanzadeh A (2010) Effects of different psychotropic agents on the central nerve growth factor protein. Iran J Basic Med Sci 13(1):202–209Google Scholar
- 56.Marsicano G, Lutz B (2006) Neuromodulatory functions of the endocannabinoid system. J Endocrinol Investig 29(3):27–46Google Scholar