熊果酸通过激活蛋白激酶 A、蛋白激酶 C、钙调蛋白依赖性蛋白激酶 II 和丝裂原活化蛋白激酶激酶 1/2 赋予小鼠抗抑郁样作用。
Ursolic acid affords antidepressant-like effects in mice through the activation of PKA, PKC, CAMK-II and MEK1/2.
机构信息
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
出版信息
Pharmacol Rep. 2017 Dec;69(6):1240-1246. doi: 10.1016/j.pharep.2017.05.009. Epub 2017 May 24.
BACKGROUND
Ursolic acid has been shown to display antidepressant-like effects in mice through the modulation of monoaminergic systems. In this study, we sought to investigate the involvement of signaling pathways on the antidepressant-like effects of ursolic acid.
METHODS
Mice were treated orally with ursolic acid (0.1mg/kg) and, 45min later they received the followings inhibitors by intracerebroventricular route: H-89 (PKA inhibitor, 1μg/mouse), KN-62 (CAMK-II inhibitor, 1μg/mouse), chelerythrine (PKC inhibitor, 1μg/mouse), U0126 (MEK1/2 inhibitor, 5μg/mouse), PD98059 (MEK1/2 inhibitor, 5μg/mouse), wortmannin (PI3K irreversible inhibitor, 0.1μg/mouse) or LY294002 (PI3K inhibitor, 10 nmol/mouse). Immobility time of mice was registered in the tail suspension test (TST).
RESULTS
The anti-immobility effect of ursolic acid in the TST was abolished by the treatment of mice with H-89, KN-62, chelerythrine, U0126 or PD98059, but not with wortmannin or LY294002.
CONCLUSIONS
These results suggest that activation of PKA, PKC, CAMK-II, MEK1/2 may underlie the antidepressant-like effects of ursolic acid.
背景
熊果酸已被证明通过调节单胺能系统在小鼠中显示出抗抑郁样作用。在这项研究中，我们试图研究信号通路在熊果酸抗抑郁样作用中的参与。
方法
小鼠经口给予熊果酸（0.1mg/kg），45 分钟后，通过脑室内途径给予以下抑制剂：H-89（PKA 抑制剂，1μg/只）、KN-62（CAMK-II 抑制剂，1μg/只）、Chelerythrine（PKC 抑制剂，1μg/只）、U0126（MEK1/2 抑制剂，5μg/只）、PD98059（MEK1/2 抑制剂，5μg/只）、wortmannin（PI3K 不可逆抑制剂，0.1μg/只）或 LY294002（PI3K 抑制剂，10nmol/只）。在悬尾试验（TST）中记录小鼠的不动时间。
结果
熊果酸在 TST 中的抗不动作用被 H-89、KN-62、Chelerythrine、U0126 或 PD98059 处理的小鼠消除，但不被 wortmannin 或 LY294002 消除。
结论
这些结果表明，PKA、PKC、CAMK-II、MEK1/2 的激活可能是熊果酸抗抑郁样作用的基础。
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