Planta Med 2009; 75(14): 1482-1488
DOI: 10.1055/s-0029-1185797
Pharmacology
Original Paper
© 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

Giangiacomo Beretta1 [*] , Giuseppe Rossoni2 [*] , Natale Alfredo Santagati3 , Roberto Maffei Facino1
  • 1Department of Pharmaceutical Sciences “Pietro Pratesi”, University of Milan, Milan, Italy
  • 2Department of Pharmaceutical Sciences, University of Catania, Catania, Italy
  • 3Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy
Further Information

Publication History

received February 22, 2009 revised April 28, 2009

accepted May 6, 2009

Publication Date:
22 June 2009 (online)

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 (6-keto-PGF) 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.

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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