A Chemically Defined 2,3-trans Procyanidin Fraction from Willow Bark Causes Redox-Sensitive Endothelium-Dependent Relaxation in Porcine Coronary Arteries

摘要

Extracts of the bark of willow species (Salix spp.) are popular herbal remedies to relieve fever and inflammation. The effects are attributed to salicin and structurally related phenolic metabolites, while polyphenols including procyanidins are suggested to contribute to the overall effect of willow bark. This study aimed at investigating the relaxant response to a highly purified and chemically defined 2,3-trans procyanidin fraction in porcine coronary arteries. The procyanidin sample produced a concentration-dependent relaxation in U46619-precontracted tissues. Relaxation was predominantly mediated through the redox-sensitive activation of the endothelial phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, leading to the subsequent activation of endothelial nitric oxide synthase (eNOS) by phosphorylation, as evidenced by Western blotting using human umbilical vein endothelial cells (HUVECs). That the relaxant response to Salix procyanidins was reactive oxygen species (ROS)-dependent with O-2(-) as the key species followed from densitometric analysis using 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA assay) and employment of various ROS inhibitors, respectively. The data also suggested the modification of intracellular Ca2+ levels and K-Ca channel functions. In addition, our organ bath studies showed that Salix procyanidins reversed the abrogation of the relaxant response to bradykinin by oxidized low-density lipoproteins (oxLDL) in coronary arteries, suggesting a vasoprotective effect of willow bark against detrimental oxLDL in pathological conditions. Taken together, our findings suggest for the first time that 2,3-trans procyanidins may contribute not only to the beneficial effects of willow bark but also to health-promoting benefits of diverse natural products of plant origin