Danshensu attenuates scopolamine and amyloid-β-induced cognitive impairments through the activation of PKA-CREB signaling in mice
Danshensu attenuates scopolamine and amyloid-β-induced cognitive impairments through the activation of PKA-CREB signaling in mice
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DOI：
10.1016/j.neuint.2019.104537
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发表时间：
2019-12-01
影响因子：
4.2
通讯作者：
Park, Se Jin
中科院分区：
文献类型：
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作者：
Bae, Ho Jung;Sowndhararajan, Kandhasamy;Park, Se Jin
阿尔茨海默病(AD)是一种重要的慢性神经退行性疾病，主要与认知功能障碍有关。目前，从传统药用植物中提取的生物活性化合物在增强认知功能方面受到了极大的关注。丹参素是一种从中草药中分离出来的酚酸，在中枢神经系统具有多种药理活性，包括抗焦虑和神经保护作用。本研究旨在探讨丹参素对东莨菪碱的改善作用。和淀粉样β蛋白(Aβ)蛋白诱导的小鼠认知障碍。丹参素(3和10 mg/kg，P.O.)在被动回避和YMaze任务中，有效地改善了东莨菪碱诱导的小鼠认知功能障碍。在一项机制研究中，丹参素抑制单胺氧化酶A(MAO-A)活性，但不抑制MAO-B。此外，丹参素治疗还可提高大脑皮层多巴胺水平以及蛋白激酶A(PKA)和cAMP反应元件结合蛋白(CREB)的磷酸化水平。此外，PKA抑制剂H89可完全阻断丹参素对东莨菪碱所致认知功能障碍的改善作用。最后，丹参素还改善了Aβ诱导的阿尔茨海默病动物模型的认知障碍。结果表明，丹参素可通过抑制MAO-A而促进多巴胺信号转导通路，如PKA和CREB，从而显著改善东莨菪碱和Aβ所致的小鼠认知功能障碍。因此，丹参素有望成为防治阿尔茨海默病的有效药物。
Alzheimer's disease (AD) is an important chronic neurodegenerative disorder and is mainly associated with cognitive dysfunction. At present, bioactive compounds from traditional medicinal plants have received much attention for the enhancement of cognitive function. Danshensu, a phenolic acid isolated from herbal medicines, has various pharmacological activities in the central nervous system, including anxiolytic-like and neuroprotective properties. The present study aimed to investigate the ameliorating effects of danshensu on scopolamine. and amyloid-beta (A beta) protein-induced cognitive impairments in mice. Danshensu (3 and 10 mg/kg, p.o.) effectively ameliorated scopolamine-induced cognitive dysfunction in mice, as measured in passive avoidance and Ymaze tasks. In a mechanistic study, danshensu inhibited monoamine oxidase A (MAO-A) activity but not MAO-B. Additionally, danshensu treatment increased the dopamine level and the phosphorylation levels of protein kinase A (PKA) and cAMP response element binding protein (CREB), in the cortex of the brain. Furthermore, the ameliorating effect of danshensu against scopolamine-induced cognitive impairment was fully blocked by H89, a PKA inhibitor. Finally, danshensu also ameliorated A beta-induced cognitive impairments in an animal model of AD. The results revealed that danshensu treatment significantly improved scopolamine and A beta-induced cognitive impairments in mice by facilitation of dopamine signaling cascade such as PKA and CREB due to MAO-A inhibition. Thus, danshensu could be used as a promising therapeutic agent for preventing and treating AD.