Cytoprotective and Anti-Oxidative Stress Capacity of South American Medicinal Plant Brunfelsia grandiflora in Endothelial Cells

Abstract

Background: Oxidative stress is a potential cause of cardiovascular pathologies, so the protection of endothelial cells and vascular tissues is essential to avoid such conditions, perhaps with the use of natural compounds rich in phenolic compounds with a proven high antioxidant capacity. The present study was designed to show the cytoprotective capacity of phenolic extracts from the plant Brunfelsia grandiflora, as well as describe its antioxidant defense mechanisms and the expression of some molecular markers involved in cellular protection. Methods: Human EA.hy926 cells were exposed to Brunfelsia grandiflora (B. grandiflora) extract (1, 10, 25, 50, 100, and 200 μg/mL) in co-treatment (22 h with 100 μM tert-Butyl hydroperoxide (t-BOOH) and B. grandiflora concentrations) and pre-treatment (18 h of B. grandiflora concentrations and then 200 μM t-BOOH for 4 h). Cell viability, reactive oxygen species (ROS) production, nitric oxide (NO) levels, caspase 3/7 activity, malondialdehyde (MDA) concentration, and reduction in reduced glutathione (GSH) levels, glutathione peroxidase (GPx), and glutathione reductase (GR) activity were measured, and real-time PCR molecular assays superoxide dismutase (SOD2), nuclear factor E2-related factor (NRF2), BCL-2-associated X protein (BAX), and B-cell lymphoma 2 (BCL2) were performed. Data were analyzed via one-way ANOVA followed by Tukeys post hoc test. Results: B. grandiflora bark extract, mainly at concentrations of 25, 50, 100, and 200 μg/mL, significantly (p < 0.05) reversed (pre-treatment and co-treatment) the deleterious effects of t-BOOH on EA.hy926 endothelial cells, which were significantly decreased cell viability, GSH activity, and SOD2 and NRF2 expression (p < 0.05); and significantly increased levels of ROS, NO, MDA, caspase-3/7 activity, GPx activity, GR activity, and the BAX/BCL2 ratio (p < 0.05). Conclusions: B. grandiflora extract was able to reduce the deleterious effects of t-BOOH on EA.hy926 endothelial cells, which may indicate its potential phytotherapeutic benefit against cytotoxic damage caused by chemical agents.