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 ...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 m RNA 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 m RNA 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.展开更多
基金financially supported by the National Natural Science Foundation of China,Nos.81671105,81873994,31727801(to RRZ)the National Key Research and Development Program of China,No.2016YFA0100800(to LMC)the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China,No.81820108013(to LMC)。
文摘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 m RNA 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 m RNA 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.
