RESUMEN
<p><b>OBJECTIVE</b>To research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.</p><p><b>METHODS</b>The effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.</p><p><b>RESULTS</b>KH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.</p><p><b>CONCLUSIONS</b>KH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.</p>
Asunto(s)
Animales , Masculino , Enfermedad de Alzheimer , Quimioterapia , Patología , Péptidos beta-Amiloides , Angelica , Química , Encéfalo , Patología , Factor Neurotrófico Derivado del Encéfalo , Metabolismo , Disfunción Cognitiva , Quimioterapia , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Metabolismo , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , Memoria a Corto Plazo , Ratones Endogámicos C57BL , Neurogénesis , Neuroglía , Metabolismo , Patología , Neuronas , Metabolismo , Patología , Fármacos Neuroprotectores , Farmacología , Usos Terapéuticos , Fosforilación , Fitoterapia , Extractos Vegetales , Farmacología , Usos Terapéuticos , Placa Amiloide , Quimioterapia , Patología , Transducción de SeñalRESUMEN
The mechanism of Western medicine that is commonly used for pain relief is well-known. However, very little is known for oriental herbs, and even less is known for mixture of the two. We investigated the combinational effect of 3 kinds of oriental herbs, usually used for the control of headache, and acetaminophen to relieve headache in microglia cell line, BV2. Lipopolysaccharide (LPS) stimulation induced to produce nitrite and increased the expression of inflammation-related factors like inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) in murine microglia cell line, BV2. Oriental herbs such as Angelica tenuissima, Angelica dahurica, and Scutellaria baicalensis reduced the production of nitric oxide and the expression of COX-2. Moreover, a treatment of acetaminophen combined with oriental herbs was more decreased the COX-2 expression, and its product, prostaglandin E2 production in BV2 cells. Therefore, a combined treatment of oriental herbs such as A. tenuissima, A. dahurica, and S. baicalensis and Western medicine like acetaminophen has a synergistic effect on the decrease of LPS-induced inflammation in microglia.