Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression.
Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression.
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姜黄素和 HU-211 共封装固体脂质纳米粒对皮质酮诱导的重度抑郁症细胞和动物模型的抗抑郁作用
DOI：
10.2147/ijn.s109088
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发表时间：
2016
影响因子：
8
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
He X;Zhu Y;Wang M;Jing G;Zhu R;Wang S
重度抑郁症是一种复杂的神经精神障碍，几乎没有治疗方法。非靶向抗抑郁药物的使用引起了许多副作用，但疗效较低。更精确的靶向策略是开发基于纳米技术的药物输送系统；因此，我们使用固体脂质纳米粒(SLNS)来包裹Hu-211和姜黄素(Cur)。在皮质酮诱导的抑郁症细胞和动物模型上，研究了治疗抑郁症的双药纳米粒(CUR/SLNS-HU-211)的抗抑郁作用。细胞摄取行为分析显示，Cur/SLNS-Hu-211能有效地保护PC12细胞免受皮质酮诱导的细胞凋亡，并能释放更多的多巴胺，这可能与Cur/SLNS-Hu-211对Cur/SLNS-Hu-211高摄取有关。此外，Cur/SLNS-Hu-211还能显著缩短小鼠强迫游泳实验中的不动时间，延长小鼠旋转游泳实验中的跌倒潜伏期，并提高小鼠血液中的多巴胺水平。Cur/SLNS-Hu-211可将更多的Cur递送到脑内，从而显著增加脑组织中神经递质的水平，特别是在海马体和纹状体。Western印迹和免疫荧光结果显示，Cur/SLNS-HU-211能显著增强CB1、p-MEK1和p-ERK1/2的表达。我们的研究提示，Cur/SLNS-HU-211有可能在治疗抑郁症方面具有很大的潜力。
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.