Ana B Ramos-Hryb1, Mauricio P Cunha1, Francis L Pazini1, Vicente Lieberknecht1, Rui D S Prediger2, Manuella P Kaster1, Ana Lúcia S Rodrigues3. 1. Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil. 2. Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil. 3. Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil. Electronic address: ana.l.rodrigues@ufsc.br.
Abstract
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.
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.
Authors: Priscila B Rosa; Luis E B Bettio; Vivian B Neis; Morgana Moretti; Isabel Werle; Rodrigo B Leal; Ana Lúcia S Rodrigues Journal: Purinergic Signal Date: 2019-11-25 Impact factor: 3.765
Authors: Ana B Ramos-Hryb; Nicolle Platt; Andiara E Freitas; Isabella A Heinrich; Manuela G López; Rodrigo B Leal; Manuella P Kaster; Ana Lúcia S Rodrigues Journal: Neurochem Res Date: 2019-11-11 Impact factor: 3.996