进可治痴呆、退可抗癫痫,石杉碱甲对神经保护的神奇作用
【文献解读】
石杉碱甲(HupA)是从石杉属植物中提取的乙酰胆碱酯酶(AChE)抑制剂。此前有研究证明,它已被用于阿尔茨海默病和其他形式的痴呆症。2016年4月,哈佛医学院研究团队在期刊《Expert Review of Neurotherapeutics》发表文章综述了新提出的HupA的结构和药理特性,以及其抗炎、神经保护和抗惊厥作用的可能作用机制。
人巨噬细胞表达nAChR的α7亚单位(α7nAChR),它们的激活是胆碱(AChE)介导的抑制肿瘤坏死因子释放以减轻全身炎症反应所必需的。除了全身作用外,α7nAChR已被证明具有中枢抗炎特性。HupA通过α7nAChRs参与胆碱能介导的抗炎作用。HupA通过抑制NF-κB的激活和改善脑血管功能来减轻氧化应激引起的神经血管损伤和血脑屏障功能障碍,HupA还可抑制NF-κB的核转位,减少同侧皮质和纹状体中促炎因子的过度表达,并抑制缺血半影区胶质细胞的激活。在已建立的癫痫动物模型中,HupA还具有急性抗惊厥作用。
注:中枢烟碱受体亚型α7nAChR和α4β2nAChR对HupA作用的概述
HupA作为一种乙酰胆碱酯酶抑制剂,可以改善不同形式痴呆的认知障碍。HupA的药代动力学研究缺乏一致性,它的发行量非常小,口服后半衰期短。因此研究了其他给药途径,如鼻腔给药或经皮给药,具有安全和理想的血药浓度。鉴于四聚体AChE主要是膜结合的,可能在突触传递中起作用,HupA似乎降低了皮层的兴奋性。HupA的抗惊厥和抗炎作用机制是当前神经科学对HupA研究的核心。
【文献节选】
Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer’s disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and antic-onvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity.
页面更新:2024-03-03
本站资料均由网友自行发布提供,仅用于学习交流。如有版权问题,请与我联系,QQ:4156828
© CopyRight 2020-2024 All Rights Reserved. Powered By 71396.com 闽ICP备11008920号-4
闽公网安备35020302034903号