Keap1-Nrf2-ARE信号通路在阿尔茨海默病（Alzheimer’s disease，AD）的发生与进展中具有核心调
控功能，主要通过调节抗氧化基因表达、抑制氧化应激及神经炎症，从而减缓神经退行性损伤。锁阳黄酮
是一种天然多酚类化合物，近年来被发现可通过Keap1-Nrf2-ARE通路的多靶点作用对AD病理产生显著
改善潜力。该通路通过激活Nrf2因子，上调抗氧化酶的表达，减少氧化损伤并增强神经元保护作用。此
外，锁阳黄酮通过调控自噬途径促进Aβ蛋白沉积的清除，从而减轻Aβ引发的神经毒性，同时通过抑制
Tau蛋白的过度磷酸化，减少神经原纤维缠结的形成，维持神经细胞结构和功能稳定。锁阳黄酮还通过调
控促凋亡和抗凋亡蛋白的平衡，降低AD病程中神经元的凋亡率，进一步增强神经保护作用。其在抑制促
炎因子如IL-1β和TNF-α的表达方面也表现出显著效果，有助于减轻AD相关神经炎症反应。本文综述了
锁阳黄酮通过Keap1-Nrf2-ARE信号通路改善AD的作用机制及其在神经保护中的多重作用。
The Keap1-Nrf2-ARE signaling pathway plays a central regulatory role in the onset and
progression of Alzheimer's disease (AD). It primarily slows down neurodegenerative damage by regulating the
expression of antioxidant genes, inhibiting oxidative stress, and suppressing neuroinflammation. Cynomorium
flavonoids, a type of natural polyphenolic compound, have been discovered in recent years to possess
significant potential for improving AD pathology through multi-target effects via the Keap1-Nrf2-ARE
pathway. This pathway activates the Nrf2 factor, upregulates the expression of antioxidant enzymes, reduces
oxidative damage, and enhances neuronal protection. In addition, cynomorium flavonoids promote the
clearance of amyloid-beta (Aβ) protein deposits by regulating the autophagy pathway, thereby alleviating A
β-induced neurotoxicity. Meanwhile, they inhibit the excessive phosphorylation of Tau protein, reduce the
formation of neurofibrillary tangles, and maintain the structural and functional stability of nerve cells.
Cynomorium flavonoids also reduce neuronal apoptosis rates during the course of AD by regulating the
balance between pro-apoptotic and anti-apoptotic proteins, further enhancing neuroprotective effects. They
also exhibit significant efficacy in inhibiting the expression of pro-inflammatory cytokines such as IL-1β and
TNF-α, helping to mitigate AD-related neuroinflammatory responses. This review summarizes the mechanisms
by which cynomorium flavonoids improve AD through the Keap1-Nrf2-ARE signaling pathway and their
multiple roles in neuroprotection.
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