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 neuropatholo...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 C57 Bl/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 field 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(Neu N), Aβ1-42] of neurodegeneration were examined. The levels of glial fibrillary acidic protein(GFAP), Neu N, phosphorylation extracellular signal-regulated kinase(ERK)/ERK, brain-derived neurotrophic factor(BDNF), phosphorylation c AMP 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 deficits in the Aβ1-42-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.展开更多
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most com...Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most common forms of dementia. Clinical studies and preclinical data in the last decade proved that AD and Diabetes mellitus share a pathophysiological pathway, indicating that insulin resistance, oxidative stress and inflammatory response would increase the risks of developing AD in diabetic patients. This review presents briefly the etiology of AD and Diabetes, discusses the possible theories about the interplaying risk factors and the mechanism of action of anti-diabetic medications recommended for the treatment of AD. It is concluded that antidiabetics have good potential to improve dementia, especially in earlier AD stages. However, many of the underlying intricate molecular pathways are still unclear and thus thorough future research is required.展开更多
脑淀粉样血管病（Cerebral Amyloid Angiopa‐thy ，CAA）是一种常见于老年人的脑内微血管病变，病理特征主要是β－淀粉样蛋白（Aβ）沉积于皮层、皮层下、软脑膜血管的中膜以及外膜，血管平滑肌失去了正常的生理功能［1］。C A A 多...脑淀粉样血管病（Cerebral Amyloid Angiopa‐thy ，CAA）是一种常见于老年人的脑内微血管病变，病理特征主要是β－淀粉样蛋白（Aβ）沉积于皮层、皮层下、软脑膜血管的中膜以及外膜，血管平滑肌失去了正常的生理功能［1］。C A A 多发生于60岁以上的老年人，临床易出现反复发作或多发脑叶出血，已成为老年非高血压性脑出血的重要原因之一。伴随社会发展，人口老龄化趋势逐年加重，CAA 的发病率亦逐年增高，并且由于老年人普遍使用抗血小板、抗凝类药物，CAA 相关性脑出血日益受到临床的重视［2］。展开更多
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(No.NRF-2013R1A1A1063477)
文摘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 C57 Bl/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 field 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(Neu N), Aβ1-42] of neurodegeneration were examined. The levels of glial fibrillary acidic protein(GFAP), Neu N, phosphorylation extracellular signal-regulated kinase(ERK)/ERK, brain-derived neurotrophic factor(BDNF), phosphorylation c AMP 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 deficits in the Aβ1-42-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.
文摘Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most common forms of dementia. Clinical studies and preclinical data in the last decade proved that AD and Diabetes mellitus share a pathophysiological pathway, indicating that insulin resistance, oxidative stress and inflammatory response would increase the risks of developing AD in diabetic patients. This review presents briefly the etiology of AD and Diabetes, discusses the possible theories about the interplaying risk factors and the mechanism of action of anti-diabetic medications recommended for the treatment of AD. It is concluded that antidiabetics have good potential to improve dementia, especially in earlier AD stages. However, many of the underlying intricate molecular pathways are still unclear and thus thorough future research is required.
文摘脑淀粉样血管病（Cerebral Amyloid Angiopa‐thy ，CAA）是一种常见于老年人的脑内微血管病变，病理特征主要是β－淀粉样蛋白（Aβ）沉积于皮层、皮层下、软脑膜血管的中膜以及外膜，血管平滑肌失去了正常的生理功能［1］。C A A 多发生于60岁以上的老年人，临床易出现反复发作或多发脑叶出血，已成为老年非高血压性脑出血的重要原因之一。伴随社会发展，人口老龄化趋势逐年加重，CAA 的发病率亦逐年增高，并且由于老年人普遍使用抗血小板、抗凝类药物，CAA 相关性脑出血日益受到临床的重视［2］。
