Zhang Xiao, He Xixin, Chen Qiuhe, Lu Junfeng, Rapposelli Simona, Pi Rongbiao
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Bioorg Med Chem. 2018 Feb 1;26(3):543-550. doi: 10.1016/j.bmc.2017.12.042. Epub 2017 Dec 26.
Alzheimer's disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aβ) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids, including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD.
阿尔茨海默病（AD）是一种复杂的慢性进行性中枢神经系统退行性疾病，也是一个全球性的公共卫生问题，其特征通常是认知功能障碍伴发攻击行为和抑郁，甚至可能导致死亡。由于目前尚无针对AD的有效治疗策略，因此对其应给予更多关注。AD的特点是胆碱能神经元丧失、β-淀粉样肽（Aβ）斑块和神经原纤维缠结，人们建立了多种假说以解释AD的发病机制。包括咖啡酸（CA）和阿魏酸（FA）在内的羟基肉桂酸广泛分布于天然植物和水果中。CA和FA具有多种药理活性，包括抗炎、抗氧化、神经保护、抗淀粉样蛋白聚集等。所有这些药理活性均与AD的治疗相关。在此，我们总结了CA和FA及其杂合物作为多靶点导向配体（MTDLs）抗AD的药理活性。同时还讨论了CA和FA未来的应用前景，希望能为基于CA和FA的MTDLs抗AD药物研发提供有益信息。
