Z-Guggulsterone Produces Antidepressant-Like Effects in Mice through Activation of the BDNF Signaling Pathway.
Z-Guggulsterone Produces Antidepressant-Like Effects in Mice through Activation of the BDNF Signaling Pathway.
复制标题
DOI：
10.1093/ijnp/pyx009
复制
发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Liu FG;Hu WF;Wang JL;Wang P;Gong Y;Tong LJ;Jiang B;Zhang W;Qin YB;Chen Z;Yang RR;Huang C
Z-guggulsterone是一种从没药树的树胶树脂中提取的活性化合物，已被证明可以通过激活脑源性神经营养因子信号通路来改善动物记忆缺陷。在这里，我们研究了Z-guggulsterone在慢性不可预测的应激抑郁症小鼠模型中的抗抑郁样作用。采用小鼠悬尾试验和强迫游泳试验评价Z-香豆甾酮的作用。以氟西汀为阳性对照，在慢性不可预见性应激抑郁症模型上观察Z-香豆甾酮的作用。研究了慢性不可预测应激/Z-guggulsterone治疗后海马神经发生以及脑源性神经营养因子信号通路的变化。色氨酸羟化酶抑制剂和酪氨酸激酶B抑制剂也被用于探讨Z-guggulsterone的抗抑郁样机制。Z-guggulsterone（10，30 mg/kg）给药对小鼠悬尾试验和强迫游泳试验中慢性不可预测的应激诱导的不动时间的增加具有保护作用，并且还逆转了蔗糖偏好实验中蔗糖摄入量的减少。给予Z-guggulsterone（10、30 mg/kg）可防止慢性不可预测应激引起的海马和皮质中脑源性神经营养因子蛋白表达水平以及cAMP反应元件结合蛋白、细胞外信号调节激酶1/2和蛋白激酶B磷酸化水平的降低。Z-guggulsterone（10，30毫克/公斤）治疗也改善海马神经元在慢性不可预测的压力处理的小鼠。阻断脑源性神经营养因子信号，而不是单胺能系统，减弱了Z-guggulsterone的抗抑郁样作用。Z-guggulsterone通过激活脑源性神经营养因子信号通路和上调海马神经发生表现出抗抑郁活性。
Z-guggulsterone, an active compound extracted from the gum resin of the tree Commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress mouse model of depression. The effects of Z-guggulsterone were assessed in mice with the tail suspension test and forced swimming test. Z-guggulsterone was also investigated in the chronic unpredictable stress model of depression with fluoxetine as the positive control. Changes in hippocampal neurogenesis as well as the brain-derived neurotrophic factor signaling pathway after chronic unpredictable stress/Z-guggulsterone treatment were investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressant-like mechanisms of Z-guggulsterone. Z-guggulsterone (10, 30 mg/kg) administration protected the mice against the chronic unpredictable stress-induced increases in the immobile time in the tail suspension test and forced swimming test and also reversed the reduction in sucrose intake in sucrose preference experiment. Z-guggulsterone (10, 30 mg/kg) administration prevented the reductions in brain-derived neurotrophic factor protein expression levels as well as the phosphorylation levels of cAMP response element binding protein, extracellular signal-regulated kinase 1/2, and protein kinase B in the hippocampus and cortex induced by chronic unpredictable stress. Z-guggulsterone (10, 30 mg/kg) treatment also improved hippocampal neurogenesis in chronic unpredictable stress-treated mice. Blockade of the brain-derived neurotrophic factor signal, but not the monoaminergic system, attenuated the antidepressant-like effects of Z-guggulsterone. Z-guggulsterone exhibits antidepressant activity via activation of the brain-derived neurotrophic factor signaling pathway and upregulation of hippocampal neurogenesis.