He Xiao-Lie, Yang Li, Wang Zhao-Jie, Huang Rui-Qi, Zhu Rong-Rong, Cheng Li-Ming
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.
Neural Regen Res. 2021 Mar;16(3):537-542. doi: 10.4103/1673-5374.293155.
Dexanabinol (HU-211) is an artificially synthesized cannabinoid derivative that exerts neuroprotective effects through anti-inflammatory and antioxidant effects. Curcumin exhibits antidepressant effects in the treatment of major depressive disorder. To investigate the antidepressant effects of solid lipid nanoparticles loaded with both curcumin and dexanabinol, and the underlying mechanisms associated with this combination, we established wild-type (CBR1) and cannabinoid receptor 1 (CBR1) knockout (CBR1) mouse models of major depressive disorder, through the intraperitoneal injection of corticosterone, for 3 successive days, followed by treatment with intraperitoneal injections of solid lipid nanoparticles loading with curcumin (20 mg/kg) and dexanabinol (0.85 mg/kg), for 2 successive days. Our results revealed that solid lipid nanoparticle loading with curcumin and dexanabinol increased the mRNA and protein expression levels of the mature neuronal markers neuronal nuclei, mitogen-activated protein 2, and neuron-specific beta-tubulin III, promoted the release of dopamine and norepinephrine, and increased the mRNA expression of CBR1 and the downstream genes Rasgef1c and Egr1, and simultaneously improved rat locomotor function. However, solid lipid nanoparticles loaded with curcumin and dexanabinol had no antidepressant effects on the CBR1 mouse models of major depressive disorder. This study was approved by the Institutional Ethics Committee of Tongji Hospital of Tongji University, China (approval No. 2017-DW-020) on May 24, 2017.
右大麻酚（HU - 211）是一种人工合成的大麻素衍生物，通过抗炎和抗氧化作用发挥神经保护作用。姜黄素在治疗重度抑郁症时具有抗抑郁作用。为了研究负载姜黄素和右大麻酚的固体脂质纳米颗粒的抗抑郁作用及其相关潜在机制，我们通过连续3天腹腔注射皮质酮建立了野生型（CBR1）和大麻素受体1（CBR1）基因敲除（CBR1）的重度抑郁症小鼠模型，随后连续2天腹腔注射负载姜黄素（20 mg/kg）和右大麻酚（0.85 mg/kg）的固体脂质纳米颗粒进行治疗。我们的结果显示，负载姜黄素和右大麻酚的固体脂质纳米颗粒增加了成熟神经元标志物神经细胞核、有丝分裂原活化蛋白2和神经元特异性β - 微管蛋白III的mRNA和蛋白表达水平，促进了多巴胺和去甲肾上腺素的释放，增加了CBR1及其下游基因Rasgef1c和Egr1的mRNA表达，同时改善了大鼠运动功能。然而，负载姜黄素和右大麻酚的固体脂质纳米颗粒对CBR1基因敲除的重度抑郁症小鼠模型没有抗抑郁作用。本研究于2017年5月24日获得中国同济大学附属同济医院机构伦理委员会批准（批准号：2017 - DW - 020）。
