1)Key Laboratory of Tobacco Biological Effects, National Tobacco Quality Supervision &Test Center, Zhengzhou 450006, China;2)Beijing Life Science Academy, Beijing 102200, China
This work was supported by grants from Beijing Institute of Life Science and Technology (2023000CB0030, 2023100CC0180, 2024500CC0070).
Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β-amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β-secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.
ZHANG Yu-Meng, TIAN Yu-Shan, LI Jie, MU Wen-Jun, YIN Chang-Feng, CHEN Huan, HOU Hong-Wei. The Mechanisms of Quercetin in Improving Alzheimer’s Disease[J]. Progress in Biochemistry and Biophysics,2025,52(2):334-347
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