Tangzhiqing-mediated NRF2 reduces autophagy-dependent ferroptosis to mitigate diabetes-related cognitive impairment neuronal damage

Diabetes is a chronic condition defined by the body's inability to process glucose. The most common form, diabetes mellitus, reflects the body's Insulin resistance, which leads to long-term raised glucose blood levels. These levels can cause oxidative damage, cell stress, and excessive Autophagy throughout the body, including the nervous system. Diabetes-related cognitive impairment (DCI) results from chronic elevation of blood glucose, and as diabetes cases continue to rise, so too do comorbidities such as DCI. Although there are medications to address high blood glucose, there are few that can inhibit excessive Autophagy and cell death. Therefore, we investigated if the Traditional Chinese Medicine, Tangzhiqing (TZQ), can reduce the impact of DCI in a high-glucose cell model. We used commercially available kits to evaluate cell viability, mitochondrial activity, and oxidative stress. We found that TZQ treatment increased cell viability, ensured continued mitochondrial activity, and reduced Reactive Oxygen Species. We also found that TZQ functions by increasing NRF2 activity, which decreases the ferroptotic-associated pathways that involve p62, HO-1, and GPX4. Therefore, TZQ should be further investigated for its role in reducing DCI.