The Protective Effects of Hyperoside on Ang II-mediated Apoptosis of Bend.3 Cells and Injury of Blood-Brain Barrier Model in Vitro

BACKGROUND:Hypertension and its associated dysfunction of the blood-brain barrier (BBB) are considered to contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), as an important vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension, but also causes BBB leakage, cSVD and its related cognitive impair. Hyperoside (Hyp), a flavone glycoside, has antioxidant, antiphlogistic and anti-apoptosis effects. In this study, we investigate the protection of Hyp on apoptosis of bEnd.3 cells and BBB disruption in vitro induced by Ang II.METHODS:We used bEnd.3 cells to imitate a BBB monolayer model and explored the protection of Hyp on Ang II-induced BBB leakage. The apoptotic activity was assessed by TUNEL staining and flow cytometry. The expression of apoptosis pathway related proteins, tight junction proteins and transcytosis related proteins were detected by western blot assay. The BBB model permeability was detected through measuring the flux of sodium fluorescein (Na-F).RESULTS:We found that Hyp can not only effectively inhibit the apoptosis of bEnd.3 induced by Ang II, but also protect the structural soundness and functional integrity of BBB model by affecting the expression levels of junctional adhesion molecule A (JAM-A), Claudin-5, zonula occludens-1 (ZO-1), Caveolin-1 (Cav-1) and major facilitator superfamily domain-containing protein 2a (Mfsd2a).CONCLUSION:Hyp might be a potent compound for preventing Ang II-induced BBB disruption.