Anti-Ischemic Activity and Endothelium-Dependent Vasorelaxant Effect of Hydrolysable Tannins from the Leaves ofRhus coriaria(Sumac) in Isolated Rabbit Heart and Thoracic Aorta

Abstract

The aim of this work was to investigate the cardioprotective activity of hydrolysable gallotannins from Rhus coriaria L. leaves extract (RCLE) in isolated rabbit heart preparations, submitted to low-flow ischemia/reperfusion damage. RCLE induces a dose-dependent normalization of coronary perfusion pressure (CPP), reducing left ventricular contracture during ischemia, and improving left ventricular developed pressure and the maximum rate of rise and fall of left ventricular pressure at reperfusion. Creatinine kinase (CK) and lactate dehydrogenase (LDH) outflow were significantly reduced during reperfusion. In parallel there was a rise in the release of the cytoprotective 6-ketoprostaglandin F (1alpha) (6-keto-PGF (1alpha)) and a decrease of tumor necrosis factor-alpha (TNF-alpha), both significant only at the highest RCLE concentrations (150-500 microg/mL). The vasorelaxant activity of RCLE was studied in isolated rabbit aorta rings precontracted with norepinephrine (NE) with and without endothelium. The vasorelaxation induced by RCLE was predominantly endothelium-dependent as demonstrated by the loss of RCLE vasorelaxant ability in i) de-endothelized rings and ii) in intact aortic rings after pretreatment with NG-monomethyl- L-arginine (L-NMMA) and 1 H-[1.2.4]oxadiazolo[4.3- A]quinoxalin-1-one (ODQ). The inhibition of vasorelaxation in intact rings by indomethacin (INDO) demonstrates the ability of RCLE to modulate the coronary endothelium cyclooxygenase (COX) pathway. The K-ATP channel antagonist glibenclamide (GLIB) was ineffective. The antioxidant activity of RCLE, investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model and in living cell systems (rat erythrocytes), was stronger than that of gallic acid, ascorbic acid and trolox. The structure of its main bioactive constituents, profiled by HPLC-ESI-HR-S, comprised a mixture of polygalloylated D-glucopyranose with different degrees of galloylation and 3- O-methylgallic acid. The cardiovascular protective effect of RCLE seems to be due to an interplay of different factors: COX pathway activation, TNF-alpha inhibition, endothelial nitric oxide synthase (eNOS) activation, and free radical and ROS scavenging.

Effects of dietary inclusion of Rhus coriaria on internal milieu of rabbits

“…Sumac contains various substances and exactly tannin and gallic acids may be responsible for the antioxidant ability of this plant. It was reported that the antioxidant activity of gallotannins from R. coriaria L. leaves’ extract was stronger than that of gallic acid (Beretta et al., 2009). Tannic acid extracted from Rhus chinensis Mill.…”

Conformation of the tridimensional structure of 1,2,3,4,6‐pentagalloyl‐β‐D‐glucopyranose (PGG) by 1H NMR, NOESY and theoretical study and membrane interaction in a simulated phospholipid bilayer: a first insight

“…PGG (purity > 98%) was obtained by semi‐preparative HPLC from a MeOH/H 2 O extract of Rhus coriaria L. (Anacardiaceae) as previously described 12. To investigate the dynamic behavior of PGG, three independent molecular dynamic simulations were done, in water, DMSO and hydrated bilayer.…”

“…Besides these effects, PGG has anti‐diabetic and anti‐obesity properties through inhibition of adipocyte differentiation and stimulation of glucose uptake through insulin‐mimicking activity 10. In addition, there are reports of gastroprotective activity by inhibition of gastric H + , K + ‐ATPase,11 a cardioprotective effect against ischemia‐reperfusion damage in isolated rabbit heart and aorta12 and antithrombotic action 13…”

The structure, occurrence and biological activity of ellagitannins: a general review

“…Studies have confi rmed a correlation between the consumption of foods rich in ellagitannins (walnuts, pomegranates) and improved cardiovascular health [Beretta et al 2009, Larossa et al 2010.…”