title: 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.
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
authors.forename: Xiaolie
authors.initials: X
authors.lastname: He
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Jing
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003345:Corticosterone / Q000009:adverse effects*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D004298:Dopamine / Q000097:blood; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D005455:Fluorescent Antibody Technique; D008055:Lipids / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D012995:Solubility; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D008055:Lipids; D018377:Neurotransmitter Agents; D013759:Dronabinol; D003474:Curcumin; C062018:HU 211; D004298:Dopamine; D003345:Corticosterone
keywords: HU-211; curcumin; dopamine; major depression; solid lipid nanoparticles