Procyanidins of Nelia meyeri SCHWANT. elicit endothelium-dependent relaxation in porcine coronary arteries by activation of the PI3/Akt signalling pathway

Nelia meyeri Schwant. (Mesembryanthemacea) is a South African succulent known to contain procyanidins [1]. The aim of this study was to examine the molecular mechanism by which the extract from leaves of this plant elicits blood vessel relaxation. For this, a highly purified fraction comprised of bi- to tetrameric flavan-3-ols was applied to porcine coronary arterial rings suspended in organ chambers containing Krebs-Henseleit solution maintained at 37°C. In endothelium-intact rings pre-contracted with the thromboxane A2 mimetic U46619, the sample produced a concentration-dependent relaxation that was abolished by mechanical removal of the endothelium. Concentration-response curves to the defined procyanidin fraction were shifted to the right in the presence of L-NAME (NG-nitro-L-arginine methyl ester), an inhibitor of eNOS. The observed relaxation was also abolished by wortmannin, an inhibitor of PI3K (phosphoinositide 3-kinase). However, the relaxant response to the Nelia extractives remained unaffected in the presence of ICI 182,780, an estrogen receptor antagonist, and pertussis toxin, an inhibitor of Gi proteins. These observations confirm the essential role of EDRF in the relaxant response to Nelia procyanidins. In addition, relaxation to the Nelia fraction was abolished by MnTMPyP, a cell permeable mimetic of superoxide dismutase but not by tiron, a superoxide anion scavenger. The relaxation was insensitive to charybdotoxin plus apamin (Ca2+-activated K+ channel blockers) but was abolished by the combination of charybdotoxin plus apamin plus L-NAME. Taking together, these findings suggest that the endothelium-dependent relaxation induced by Nelia procyanidins is mediated by EDHF and EDRF following activation of PI3/Akt.

Keywords: Nelia meyeri, procyanidins, endothelium relaxation, EDHF, EDRF

References: 1. Kolodziej H (1984) Phytochemistry 23: 1745–1752