Screening of effective ingredients of total salvianolic acids components based on in vitro blood-brain barrier model / 中草药

ABSTRACT

Objective: To establish a blood-brain barrier (BBB) model for screening the effective ingredients of total salvianolic acids components probably effecting central nervous system (CNS), so as to provide basis for the rapid high throughput screening of CNS drugs. Methods: The permeability parameters and transendothelial electrical resistance (TEER) values showed that the co-cultured human brain microvascular endothelial cells (HBMEC)/HA (human astrocytes) model was of integrity and vitality. The active components in total salvianolic acids were screened with this in vitro BBB model, and then analyzed by HPLC-MS. Results: HA induced HBMEC to produce higher TEER in the first 10 d up to 300 Ω/cm2, sodium fluorescein was used to detect the formation of tight junctions of endothelial cells, and the permeability coefficient of its cross-vitro BBB model was (2.659 ± 0.730) × 10-3 cm/min. We found that six compounds at least from total salvianolic acids could permeate across BBB model, in which danshensu, protocatechuic acid, caffeic acid, isoferulic acid, lithospermic acid, and rosmarinicacid were identified. Conclusion: The co-cultured HBMEC/HA model combined with HPLC-MS analysis is a potential tool for screening of BBB permeable drug candidates from plant-derived materials.