Abstract
Natural medicines are gaining increasing attention in drug development, yet traditional static cell models fail to mimic the dynamic mechanical microenvironment in vivo, potentially leading to misleading evaluations. This study investigated how physiological fluid shear stress influences the protective effects of Salvia miltiorrhiza extract (SME) on endothelial cells (ECs). Using a parallel plate flow chamber, ECs were exposed to 15 dyn/cm² shear stress or static conditions, followed by H₂O₂-induced oxidative damage. Cell viability was assessed via MTT and live/dead staining; morphology and cytoskeleton were examined through phalloidin/DAPI staining; oxidative markers (ROS, SOD, MDA) were quantified; and SME bioactive component uptake was analyzed using HPLC. Under shear stress, SME's protection was significantly enhanced: metabolic viability reached 86.83 ± 6.4% (vs. 72.38 ± 6.8% static), protection rate nearly doubled (68.00% vs. 34.14%), morphology improved (shape index: 0.63 ± 0.11 vs. 0.73 ± 0.11), and oxidative damage was reduced (ROS decreased to 13.73 ± 1.47; SOD increased to 41.24 U/mg; MDA decreased to 0.74 nmol/mg). HPLC revealed enhanced absorption of all compounds and uptake of two additional bioactive constituents. These findings demonstrate that physiological shear stress potentiates SME's efficacy through improved compound delivery and amplified cellular responses, advocating for shear stress-responsive screening as a physiologically relevant strategy for natural medicine evaluation.