Asiaticoside produces an antidepressantlike effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway.
Mol Med Rep
; 22(3): 2364-2372, 2020 09.
Article
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| MEDLINE
| ID: mdl-32705202
ABSTRACT
Asiaticoside is one of the triterpenoid components found in Centella asiatica that has promising neuroprotective properties. The present study aimed to evaluate the antidepressantlike properties of asiaticoside and to investigate the possible mechanisms underlying its mode of action using a mouse model of chronic unpredictable mild stress (CMS). Behavioral tests, including sucrose preference test, forced swimming test and tail suspension test, were performed to evaluate symptoms of depression. The expression levels of neurotransmitters, 5hydroxytryptamine (5HT) and norepinephrine (NE), in the hippocampus were measured by highperformance liquid chromatography. ELISA and western blotting were used to detect protein expression. It was demonstrated that asiaticoside treatment (20 and 40 mg/kg; intragastric) significantly reversed the decrease in sucrose consumption, and reduced the immobility time in tail suspension tests and forced swimming tests in CMS mice. Furthermore, asiaticoside treatment upregulated the expression of 5HT and NE in the CMS mouse model. Asiaticoside administration also downregulated the levels of interleukin (IL)1ß, IL6 and tumor necrosis factorα in the hippocampus, and reduced the phosphorylation of nuclear factor (NF)κBp65 and the expression of nodlike receptor protein 3 (NLRP3), thus decreasing the expression of mature caspase1. Furthermore, asiaticoside significantly increased the levels of cAMP and protein kinase A (PKA), and enhanced phosphorylation of the cAMPrelated specific marker vasodilatorstimulated phosphoprotein at serine 157. Therefore, asiaticoside may activate the cAMP/PKA signaling pathway to inhibit NFκB and NLRP3related inflammation. Moreover, phosphorylation of the cAMPresponsive elementbinding protein at serine 133 and the expression of brainderived neurotrophic factor were increased after asiaticoside administration. Collectively, the present results suggested that asiaticoside may play a vital role as an antidepressant and antiinflammatory agent in the CMS mouse model by regulating the cAMP/PKA signaling pathway.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Estrés Psicológico
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Triterpenos
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico
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Proteínas Quinasas Dependientes de AMP Cíclico
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Factor Neurotrófico Derivado del Encéfalo
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Antidepresivos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2020
Tipo del documento:
Article