School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Tianjin Renai College, Tianjin 301636, China.
Curr Med Chem. 2023;30(40):4586-4604. doi: 10.2174/0929867330666230125153027.
Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects the health and quality of life of the elderly. Its pathogenesis is very complex and there is still a lack of effective clinical drugs to treat or control the development of AD. Studies have shown that β-amyloid (Aβ) deposition, tau protein hyperphosphorylation, reduced levels of brain cholinergic transmitters, and oxidative stress are the main causes of AD. Furthermore, recent studies showed that metal dyshomeostasis could relate to all the above pathogenesis of AD and was a key factor in the development of AD. Natural compounds and their derivatives have multi-target therapeutic effects on AD, and they also have the advantages of low toxicity, and low cost, which are important directions for anti- AD drugs. Meanwhile, early detection may play an important role in preventing the development of AD. The concept of "theranostic agent" combining molecular imaging probes and therapeutic drugs has emerged in recent years. Fluorescence imaging has been widely studied and applied because of its non-invasive, high resolution, high sensitivity, rapid imaging, and low cost. However, at present, most of the research methods in this field use individual therapeutic or diagnostic reagents, which is not conducive to exploring the optimal treatment time window and drug efficacy. Therefore, this work reviewed the natural compounds and their derivatives which all have been studied for both the in vitro and in vivo therapeutic and diagnostic anti-AD activities. At last, structure and activity relationship (SAR) was discussed and potential AD theranostic natural agents were put forwarded to provide a more detailed theoretical basis for the further development of drugs with diagnostic and therapeutic effects in AD.
阿尔茨海默病（AD）是一种神经退行性疾病，严重影响老年人的健康和生活质量。其发病机制非常复杂，目前仍然缺乏有效的临床药物来治疗或控制 AD 的发展。研究表明，β-淀粉样蛋白（Aβ）沉积、tau 蛋白过度磷酸化、脑内胆碱能递质水平降低以及氧化应激是 AD 的主要发病原因。此外，最近的研究表明，金属离子稳态失衡可能与 AD 的所有上述发病机制有关，是 AD 发生发展的关键因素。天然化合物及其衍生物对 AD 具有多靶点的治疗作用，且具有低毒性、低成本的优点，是抗 AD 药物的重要研究方向。同时，早期检测可能在预防 AD 发展方面发挥重要作用。近年来，“治疗诊断试剂”的概念将分子成像探针与治疗药物结合在一起。由于其具有非侵入性、高分辨率、高灵敏度、快速成像和低成本等特点，荧光成像得到了广泛的研究和应用。然而，目前该领域的大多数研究方法使用单一的治疗或诊断试剂，不利于探索最佳治疗时间窗和药物疗效。因此，本工作综述了具有体外和体内治疗和诊断抗 AD 活性的天然化合物及其衍生物。最后，讨论了结构与活性关系（SAR），并提出了潜在的 AD 治疗诊断两用天然试剂，为进一步开发具有诊断和治疗作用的 AD 药物提供了更详细的理论依据。
