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蒲公英赛醇作为治疗记忆障碍和阿尔茨海默病的潜在药物:对东莨菪碱和链脲佐菌素诱导的认知功能障碍的作用

Taraxerol as a possible therapeutic agent on memory impairments and Alzheimer's disease: Effects against scopolamine and streptozotocin-induced cognitive dysfunctions.

作者信息

Berté Talita Elisa, Dalmagro Ana Paula, Zimath Priscila Laiz, Gonçalves Ana Elisa, Meyre-Silva Christiane, Bürger Cristiani, Weber Carla J, Dos Santos Diogo Adolfo, Cechinel-Filho Valdir, de Souza Márcia M

机构信息

Centro de Ciências da Saúde, CCS - Núcleo de Investigações Químico Farmacêuticas NIQFAR/UNIVALI, Rua Uruguai 458, Centro, CEP: 88302-202 Itajaí, SC, Brazil.

Centro de Ciências da Saúde, CCS - Núcleo de Investigações Químico Farmacêuticas NIQFAR/UNIVALI, Rua Uruguai 458, Centro, CEP: 88302-202 Itajaí, SC, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas/UNIVALI, Rua Uruguai 458, Centro, CEP: 88302-202 Itajaí, SC, Brazil.

出版信息

Steroids. 2018 Apr;132:5-11. doi: 10.1016/j.steroids.2018.01.002.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death, characteristic of the effect of time on biochemical neuronal function. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research, since the standard drugs have many side effects. Taraxerol (TRX) is a triterpene that has been isolated from several plant species, and its various pharmacological properties have already been identified, such the acetylcholinesterase (AChE) inhibition activity in vitro. There is a lack of information in literature that confirms the effect of TRX in an animal AD-like model. Seeking to fill this gap in the literature, in the present work we assessed the effect of TRX on AChE activity in the animals' encephalon and hippocampus. We also investigated the effect of TRX (1.77 µM/side, 0.5 μL) isolated from leaves of Eugenia umbelliflora Berg. on aversive memory impairments induced by scopolamine (2 µg/side, 0.5 µL) infused into rat hippocampus, and the effect of TRX (0.89 and 1.77 µM/side, 0.5 μL) on aversive memory impairments induced by streptozotocin (STZ) (2.5 mg/mL, 2.0 µL) infused i.c.v. into mice, using the step-down inhibitory avoidance task. We found that TRX significantly inhibited AChE activity in the animal's hippocampus. Furthermore, TRX significantly improved scopolamine and STZ-induced memory impairment. Taking together, these results confirms its AChE activity inhibition in animals and indicate that TRX has anti-amnesic activity that may hold significant therapeutic value in alleviating certain memory impairments observed in AD.

摘要

阿尔茨海默病(AD)是一种与认知障碍和胆碱能神经元死亡相关的神经退行性疾病,是时间对神经元生化功能影响的特征表现。鉴于标准药物存在诸多副作用,因此将药用植物用作预防AD的替代形式,甚至作为AD的可能治疗方法,是有趣的研究领域。蒲公英赛醇(TRX)是一种已从多种植物中分离出来的三萜类化合物,其各种药理特性已得到确认,如体外乙酰胆碱酯酶(AChE)抑制活性。文献中缺乏证实TRX在动物类AD模型中作用效果的信息。为填补文献中的这一空白,在本研究中,我们评估了TRX对动物脑和海马中AChE活性的影响。我们还研究了从伞花番樱桃叶中分离出的TRX(1.77 μM/侧,0.5 μL)对注入大鼠海马的东莨菪碱(2 μg/侧,0.5 μL)诱导的厌恶记忆损伤的影响,以及TRX(0.89和1.77 μM/侧,0.5 μL)对脑室内注入链脲佐菌素(STZ)(2.5 mg/mL,2.0 μL)诱导的小鼠厌恶记忆损伤的影响,采用了阶梯式被动回避任务。我们发现TRX显著抑制动物海马中的AChE活性。此外,TRX显著改善了东莨菪碱和STZ诱导的记忆损伤。综上所述,这些结果证实了其在动物体内的AChE活性抑制作用,并表明TRX具有抗遗忘活性,这在减轻AD中观察到的某些记忆损伤方面可能具有重要的治疗价值。

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