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DOI: 10.1055/s-0029-1185797
© Georg Thieme Verlag KG Stuttgart · New York
Anti-Ischemic Activity and Endothelium-Dependent Vasorelaxant Effect of Hydrolysable Tannins from the Leaves of Rhus coriaria (Sumac) in Isolated Rabbit Heart and Thoracic Aorta
Publication History
received February 22, 2009
revised April 28, 2009
accepted May 6, 2009
Publication Date:
22 June 2009 (online)
![](https://www.thieme-connect.de/media/plantamedica/200914/lookinside/thumbnails/10.1055-s-0029-1185797-1.jpg)
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 F1α (6-keto-PGF1α) and a decrease of tumor necrosis factor-alpha (TNF-α), both significant only at the highest RCLE concentrations (150–500 µg/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 1H-[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-α inhibition, endothelial nitric oxide synthase (eNOS) activation, and free radical and ROS scavenging.
Key words
Rhus coriaria L. - Anacardiaceae - isolated rabbit heart - ischemia‐reperfusion - cardiovascular protection - tannins
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1 Both of these authors contributed equally to this work.
Giangiacomo Beretta
Department of Pharmaceutical Sciences “Pietro Pratesi”
University of Milan
Via Mangiagalli 25
20133 Milan
Italy
Phone: + 39 02 50 31 93 09
Fax: + 39 02 50 31 75 65
Email: giangiacomo.beretta@unimi.it
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