Affiliation:
1. Osun State University
2. Ekiti State University
3. Mont Rose College-Buckinghamshire, New University
4. Leeds Community Healthcare, NHS Trust
Abstract
Abstract
In type 2 diabetes triggered by insulin resistance, cerebrovascular diseases, stroke, and neurodegenerative dementia are associated. Understanding Cucurbitacin E's (CuE) effects on the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) pathways in insulin resistance-induced neurodegeneration remains essential. Using 48 adult Wistar rats, six groups were formed: A = control; B = STZ-induced diabetes (60 mg/kg); C = STZ (60 mg/kg) + CuE (0.5 mg/kg); D = STZ (60 mg/kg) + Metformin (150 mg/kg); E = CuE only (0.5 mg/kg); and F = Metformin only (150 mg/kg). CuE's impact on insulin resistance, neuronal morphology in the prefrontal cortex (PFC), neurobehavioral changes, neuroinflammation, and PI3K/AKT signaling in the PFC was evaluated. Statistical analysis was performed using one-way ANOVA and Turkey’s post hoc test (p < 0.05 was considered significant). CuE significantly reduced blood glucose and insulin resistance. Insulin resistance linked to cognitive impairment and PFC architectural changes was mitigated by CuE. It also regulated inflammatory cytokines and prevented neuronal death. CuE improved impaired PI3K/AKT activity in the model. Cucurbitacin E showed promise in mitigating dementia caused by hyperglycemia in the prefrontal cortex. It notably reduced nuclei fragmentation, neuroinflammation, and normalized the PI3K/AKT insulin signaling pathway.
Publisher
Research Square Platform LLC
Reference45 articles.
1. Type 2 diabetes mellitus: a pathophysiologic perspective;Westman EC;Frontiers in nutrition,2021
2. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045;Sun H;Diabetes research and clinical practice,2022
3. Novel insights into the immunotherapy-based treatment strategy for autoimmune type 1 diabetes;Rathod S;Diabetology,2022
4. Type 2 diabetes mellitus;DeFronzo RA;Nature reviews Disease primers,2015
5. Prevalence of dementia in the oldest old: the Monzino 80-plus population based study;Lucca U;Alzheimer's & Dementia,2015