Cistanche flavonoids activate the Keap1-Nrf2-ARE signaling pathway in improving cognitive dysfunction in Alzheimer's disease: A review

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder closely associated with oxidative stress, which plays a pivotal role in neuronal damage and disease progression. The Keap1-Nrf2-ARE signaling pathway plays a crucial role in regulating cellular responses to oxidative stress. Keap1 inhibits Nrf2 by maintaining its low expression, thus controlling antioxidant gene expression. Cistanche flavonoids, natural polyphenolic compounds, have been shown to activate this pathway. They suppress Keap1, preventing Nrf2 degradation and promoting its translocation to the nucleus, where it activates the antioxidant response element (ARE). This process significantly increases the production of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase. Elevated enzyme levels enhance cellular antioxidant defenses, reduce oxidative damage at the cellular and neuronal levels, and improve cognitive function in AD mouse models. The study examined the molecular composition of Cistanche flavonoids and their impact on the Keap1-Nrf2-ARE pathway, revealing their potential in mitigating AD-related changes. By neutralizing free radicals and enhancing antioxidant defenses, Cistanche flavonoids may offer a promising approach to counteract AD pathology. This comprehensive analysis underscores their therapeutic potential in alleviating AD through oxidative stress reduction and antioxidant activation.