Oleracone F Alleviates Cognitive Impairment and Neuropathology in APPswe/PSEN1dE9 Mice by Reducing the Expression of Vascular Cell Adhesion Molecule and Leukocyte Adhesion to Brain Vascular Endothelial Cells.

Alzheimer's disease (AD) is the most common neurodegenerative disease and the blood-brain barrier dysfunction has been suggested as a key pathological feature of the disease. Our research group successfully established a synthetic protocol for oleracones, a novel series of flavonoids isolated from the plant extract of L. (PO). PO extract was reported to have anti-inflammatory and antioxidant effects, enhancing cognitive function. Thus, we investigated the effects and mechanism of oleracones on cognition using AD model transgenic mice (Tg; APPswe/PSEN1dE9). Oleracone F treatment significantly improved memory dysfunction in Tg mice. Oleracone F decreased the number, burden, and immunoreactivity of amyloid plaques and amyloid precursor protein (APP) protein levels in the brains of Tg mice compared to wild-type mice. Oleracone F also alleviated inflammation observed in Tg mice brains. In vitro studies in human microvascular endothelial cells (HBMVECs) demonstrated that oleracones D, E, and F blocked the elevations in VCAM-1 protein induced by tumor necrosis factor-α (TNF-α), hindering leukocyte adhesion to HBMVECs. Taken together, our results suggest that oleracones ameliorated cognitive impairment by blocking TNF-α-induced increases in VCAM-1, thereby reducing leukocyte infiltration to the brain and modulating brain inflammation.