Catalpol provides a protective effect on fibrillary Aβ 1-42 -induced barrier disruption in an in vitro model of the blood-brain barrier.

Excessive amyloid beta (A) deposition in brain is mainly responsible for cell damage and blood-brain barrier (BBB) disruption in Alzheimer's disease (AD). Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa Libosch, has neuroprotective effect against AD. It is unclear whether catalpol has a protective effect on A-induced BBB leakage. We employed an immortalized endothelial cell line (bEnd.3) and astrocytes co-culture to mimic a BBB model in vitro and investigated the effect of catalpol on BBB. We found that treatment with catalpol decreased BBB hyperpermeability induced by fibrillar A(1-42). Data from western blotting showed that catalpol prevented fibrillar A(1-42)-induced bEnd.3 cell apoptosis through mitochondria-dependent and death receptor pathways; decreased the levels of matrix metalloproteinases (MMPs), MMP-2, MMP-9, and the receptor for advanced glycation end products; and increased the levels of tight junction proteins (ZO-1, occludin, and claudin-5), low-density lipoprotein receptor-related protein 1, and P-glycoprotein in fibrillar A(1-42)-treated bEnd.3 cells. Moreover, catalpol also enhanced soluble A efflux across the fibrillar A(1-42)-treated bEnd.3 cells BBB monolayer model. Altogether, our results suggest that catalpol alleviate fibrillar A(1-42)-induced BBB disruption, enhance soluble A clearance, and offer a feasible therapeutic application in AD treatment.