Minji Choi1, Younghyurk Lee1, Seung-Hun Cho2. 1. Department of Psychiatry, Hospital of Korean Medicine, Kyung Hee University Medical Center, Seoul, 130-872, South Korea. 2. Department of Psychiatry, Hospital of Korean Medicine, Kyung Hee University Medical Center, Seoul, 130-872, South Korea. chosh@khmc.or.kr.
Abstract
OBJECTIVE: To research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics. METHODS: 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 (Aβ1-42) 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 Aβ1-42-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ1-42] 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. RESULTS: KH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ1-42, and inhibited neuronal loss and neuroinflammatory response in the Aβ1-42-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. CONCLUSIONS: KH032 attenuated cognitive defificits in the Aβ1-42-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.
OBJECTIVE: To research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics. METHODS: 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 (Aβ1-42) 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 Aβ1-42-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ1-42] 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. RESULTS:KH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ1-42, and inhibited neuronal loss and neuroinflammatory response in the Aβ1-42-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. CONCLUSIONS:KH032attenuated cognitive defificits in the Aβ1-42-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.
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