Dietary Flavonoids Protect Human Brain Microvascular Endothelial Cell from Oxidative Stress-induced Dysfunction

Abstract

Blood-brain barrier (BBB) is involved in the pathogenesis of many neurological diseases and is particularly susceptible to oxidative stress. Primary human brain microvascular endothelial cell (HBMEC), the major component of BBB, plays a major role in its creation and maintenance. Growing evidence suggests an inverse relationship between dietary flavonoids intake and cardiovascular risk, possibly due to their antioxidative effects. This study systematically investigated the effects of four common and abundant flavonoids in HBMEC under oxidative stress microenvironment. The results showed that H 2 O 2 resulted in a 70% inhibition of capillary network formation, 80% growth reduction, and a 2.5-fold increase in apoptosis. However, the addition of quercetin, apigenin, and genistein mitigated H 2 O 2 -induced dysfunctions in HBMEC by 80% to 95%. In addition, quercetin, apigenin and genistein exhibited a 90% reversal of H 2 O 2 -induced oxidative stress, oxidative lipid and DNA damage. In contrast, myricetin neither reversed H 2 O 2 -induced oxidative stress nor displayed any protective effects in HBMEC. Interestingly, quercetin and apigenin caused a 2-fold increase in NRF2 and NQO1 levels in HBMEC whereas genistein had no impact on their levels. Our research provides pre-clinical evidence indicating that certain flavonoids possess antioxidant properties and alleviate oxidative stress-induced dysfunction in brain endothelium. It highlights the positive impact of flavonoids on the BBB and offers potential therapeutic strategies for treating neurological diseases.