Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor associated with more than 200 genes. It helps to support a healthy inflammatory response, antioxidative status, and preserve homeostasis in the presence of cellular stress. Recent research indicates that certain micronutrients such as quercetin may support the Nrf2 pathway and neurological health. 

Berries, particularly dark berries, contain a relatively high amount of health-supportive compounds. These include flavonoids such as quercetin, which have been shown to support cellular health, antioxidative status, and mitochondrial health. A recently published review article by Bayazid and colleagues explored the potential efficacy of quercetin on brain health. 

Research indicates that quercetin may play a direct role in support of neuronal health and antioxidative status. Quercetin has been shown to help modulate Nrf2/heme oxygenase-1 (HO1) signaling pathways in neuronal cells, which may help support a healthy response to neuroinflammation. The Nrf2/HO1 pathway has been associated in research with helping to prevent certain aspects of neurodegeneration. 

In animal studies, the administration of quercetin has been shown to help improve parameters related to cognition, spatial learning, neuroplasticity, and memory. It has also been shown to help decrease oxidative stress through the Nrf2/antioxidant responsive element (ARE) pathway. Neuronal cell loss can occur due to mitochondrial dysfunction triggered by oxidative stress-related signaling cascades. 

Neurodegeneration has been associated with the upregulation of P-53, and quercetin may help suppress hyperactive P-53 in the body. Quercetin also helps downregulate pro-inflammatory cytokines, such as tumor necrosis factor-α and certain interleukins (ILs) including IL-1β. Quercetin also helps regulate nuclear factor-kappa B and has been shown to help support the attenuation of astrogliosis and microgliosis. In animal studies, quercetin has been observed to help prevent the accumulation of amyloid-β (Aβ) through the stabilization of apolipoprotein E. Aβ has been associated with neurodegenerative diseases such as Alzheimer’s disease (AD).

Quercetin may also help reduce reactive oxygen species (ROS) by increasing the activity of SIRT1. SIRT1 activation may also help modulate the expression of Aβ and tau, another molecule associated with AD. An animal study involving AD mouse models reported improvements in markers related to cognitive function and neurodegeneration after quercetin administration. Another study involving quercetin showed improvements in signaling pathways related to AD progression, including SIRT1/FoxO.

More research is needed, particularly in the clinical setting; however, quercetin may help support antioxidative status and a normal inflammatory response. Quercetin may also help support Nrf2 pathways and neurological health. 

By Colleen Ambrose, ND, MAT