中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (12): 2582-2591.doi: 10.4103/1673-5374.373680

• 综述:退行性病与再生 • 上一篇    下一篇

天然黄酮类化合物靶向干预阿尔茨海默病的神经炎症

  

  • 出版日期:2023-12-15 发布日期:2023-06-14
  • 基金资助:
    陕西省自然科学基金重点项目(2022JZ-46)和中央高校基本科研业务费(GK202103079)

The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer’s disease: a narrative review

Qian Zhang*, Yaping Yan   

  1. National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China; Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education; College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi Province, China
  • Online:2023-12-15 Published:2023-06-14
  • Contact: Qian Zhang, PhD, zq-melody@163.com.
  • Supported by:
    This work was supported by the Key Program of Natural Science Foundation of Shaanxi Province of China, No. 2022JZ-46; the Fundamental Research Funds for the Central Universities, No. GK202103079 (both to QZ).

摘要:

阿尔茨海默病是一种影响许多老年人的神经退行性疾病,以记忆丧失、进行性认知障碍和各种行为障碍为特征。虽然阿尔茨海默病的潜在病理机制十分复杂,尚未被完全阐明。Aβ淀粉样蛋白级联假说和tau蛋白异常磷酸化假说是目前被广泛接受为两种病理假说。近年来,神经炎症在阿尔茨海默病发病机制中的重要作用逐渐被揭示。研究表明,阿尔茨海默病中的炎症微环境主要由小胶质细胞、星形胶质细胞、补体系统、多种趋化因子和细胞因子、活性氧介质等共同构成。恶化的炎症微环境在上述两种假说中都是重要的危险因子,能促进Aβ斑块的沉积,加快tau蛋白异常磷酸化,形成恶性循环,推动病理进程、增加疾病严重程度。黄酮类化合物是一种存在于植物中的次生代谢产物,具有多种生物活性。研究表明,多种天然黄酮类化合物可以靶向上述阿尔茨海默病神经炎症过程中的一个或多个环节,最终减少Aβ的聚集、沉积,或降低tau的磷酸化水平、抑制神经缠结,从而发挥良好的干预效果。因此,文章总结了13种来源于植物或药材中的天然黄酮类化合物对阿尔茨海默病神经炎症的作用及机制。这些化合物包括芹菜素、木犀草素、柚皮素、槲皮素、桑色素、山奈酚、非瑟酮、异槲皮苷、黄芪苷、芦丁、淫羊藿苷、芒果苷、花青素。关注并继续探讨黄酮类化合物对神经炎症的作用及机制,有助于阿尔茨海默病的深入研究和相关药物的开发。

https://orcid.org/0000-0002-3859-6503 (Qian Zhang)

Abstract: Alzheimer’s disease is a neurodegenerative disease that affects a large proportion of older adult people and is characterized by memory loss, progressive cognitive impairment, and various behavioral disturbances. Although the pathological mechanisms underlying Alzheimer’s disease are complex and remain unclear, previous research has identified two widely accepted pathological characteristics: extracellular neuritic plaques containing amyloid beta peptide, and intracellular neurofibrillary tangles containing tau. Furthermore, research has revealed the significant role played by neuroinflammation over recent years. The inflammatory microenvironment mainly consists of microglia, astrocytes, the complement system, chemokines, cytokines, and reactive oxygen intermediates; collectively, these factors can promote the pathological process and aggravate the severity of Alzheimer’s disease. Therefore, the development of new drugs that can target neuroinflammation will be a significant step forward for the treatment of Alzheimer’s disease. Flavonoids are plant-derived secondary metabolites that possess various bioactivities. Previous research found that multiple natural flavonoids could exert satisfactory treatment effects on the neuroinflammation associated with Alzheimer’s disease. In this review, we describe the pathogenesis and neuroinflammatory processes of Alzheimer’s disease, and summarize the effects and mechanisms of 13 natural flavonoids (apigenin, luteolin, naringenin, quercetin, morin, kaempferol, fisetin, isoquercitrin, astragalin, rutin, icariin, mangiferin, and anthocyanin) derived from plants or medicinal herbs on neuroinflammation in Alzheimer’s disease. As an important resource for the development of novel compounds for the treatment of critical diseases, it is essential that we focus on the exploitation of natural products. In particular, it is vital that we investigate the effects of flavonoids on the neuroinflammation associated with Alzheimer’s disease in greater detail. 

Key words: Alzheimer’s disease, astrocytes, flavonoids, microglia, natural products, neuroinflammation