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.
PDF(690 KB)
