Targeting the EndocannabinoidCB1 Receptor System For Treating Major Depression Through Antidepressant Activities of Curcumin and Dexanabinol-Loaded Solid Lipid Nanoparticles.
This study investigated the underlying mechanisms of the antidepressant effects of curcumin and dexanabinol-loaded solid lipid nanoparticles in corticosterone-induced cell and mice depression models. Curcumin and dexanabinol-loaded solid lipid nanoparticles (CurSLNs-HU-211) were synthesized via an emulsifcation and low-temperature solidification method. Antidepressant activities of nanoparticles in a corticosterone-induced major depression model were investigated by MTT assay, cellular uptake by flow cytometry, behaviour by Forced Swimming Test and rotarod test, neurotransmitters by High Performance Liquid Chromatography, Western blotting, qPCR and immunofluorescence. Treatment with CurSLNs-HU-211 induced greater dopamine (DA)5-hydroxytryptamine (5-HT) release with reduced corticosterone-induced apoptotic cell death in PC12 cells. Additionally, in vivo CurSLNs-HU-211 significantly induced recovery from depressive behaviour with increased DA5-HT levels, CB1 mRNA levels and CB1, p-MEK1 and p-ERK12 protein expression levels in the hippocampus and striatum. CurSLNs-HU-211 improved CB1 expression and inspired the proliferation of astrocytes in the hippocampus and striatum, exerted neuroprotective effects by preventing corticosterone -induced BDNFNeuN expression reduction. Our study implies that CurSLNs-HU-211 may be a useful approach for treatment of major depression.