Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression

Abstract

Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression. Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and can release more dopamine, which may be associated with the higher uptake of Cur/SLNs-HU-211 shown by cellular uptake behavior analysis. Additionally, Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test, enhanced fall latency in rotarod test, and improved the level of dopamine in mice blood. Cur/SLNs-HU-211 can deliver more Cur to the brain and thus produce a significant increase in neurotransmitters level in brain tissue, especially in the hippocampus and striatum. The results of Western blot and immunofluorescence revealed that Cur/SLNs-HU-211 can significantly enhance the expression of CB1, p-MEK1, and p-ERK1/2. Our study suggests that Cur/SLNs-HU-211 may have great potential for major depression treatment.

Oleuropein Reverses Repeated Corticosterone-Induced Depressive-Like Behavior in mice: Evidence of Modulating Effect on Biogenic Amines

“…Recent evidences suggest that oxidative stress might contribute significantly to the pathogenesis of many psychiatric disorders, including depression. This was supported by data reporting that major depression is associated with lowered levels of several endogenous antioxidants, including vitamin E, zinc and coenzyme Q10, along with reduced antioxidant enzymes such as glutathione peroxidase 3 . Moreover, reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been shown to modulate the levels and activities of biogenic amines; norepinephrine, serotonin, and dopamine 4 .…”

Benefits of curcumin in brain disorders

“…Curcumin has shown to possess a strong antidepressant activity in animal models of depression . It acts by inhibiting the expression of MAO‐A and MAO‐B enzymes which results in increase the levels of norepinephrine, serotonin, and dopamine .…”

“…Curcumin has shown to possess a strong antidepressant activity in animal models of depression. [104][105][106][107] It acts by inhibiting the expression of MAO-A and MAO-B enzymes which results in increase the levels of norepinephrine, serotonin, and dopamine. 108 Curcumin's antidepressant activity is produced by ERK regulated increase in the expression of brain-derived neurotrophic factor (BDNF) expression in the amygdala of mice.…”

Curcumin in antidepressant treatments: An overview of potential mechanisms, pre‐clinical/clinical trials and ongoing challenges

“…[128][129][130] For instance, curcumin encapsulated in poly (lactic-coglycolic acid) nanoparticles not only offers significantly better BBB penetration in rat models but also shows longer retained time in the cerebral cortex and hippocampus when compared with that of curcumin molecules. 131 Besides, He et al 132 applied solid lipid nanoparticles to co-load HU-211 and curcumin that can deliver more curcumin to the brain and increase the neurotransmitter level in brain tissue. At present, further investigations are still urgently required to better understand the total potentials of these curcumin-containing nanoplatforms and accelerate their progress from the laboratory bench to the commercial and clinical market.…”