Pharmacological reports : PR · 2017
Ursolic acid affords antidepressant-like effects in mice through the activation of PKA, PKC, CAMK-II and MEK1/2.
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Ramos-Hryb Ana B, Cunha Mauricio P, Pazini Francis L, Lieberknecht Vicente, Prediger Rui D S, Kaster Manuella P, Rodrigues Ana Lúcia S
Аннотация
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.
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.
Предметные рубрики MeSH
Administration, OralAnimalsAntidepressive AgentsBehavior, AnimalCalcium-Calmodulin-Dependent Protein Kinase Type 2Cyclic AMP-Dependent Protein KinasesDepressionDisease Models, AnimalHindlimb SuspensionMAP Kinase Kinase 1MAP Kinase Kinase 2MaleMiceProtein Kinase CSignal TransductionTriterpenesUrsolic Acid