Download PDF
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)

Also available at
    Permissions and Reprints

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

References

  • 1 Bozan B, Kosar M, Tunalier Z, Ozturk N, Baser K HC. Antioxidant and free radical scavenging activities of Rhus coriaria and Cinnamomum cassia extracts.  Acta Alimentaria. 2003;  32 5-61
    PubMedSearch in Google Scholar
  • 2 Candan F, Sökmen A. Effects of Rhus coriaria L. (Anacardiaceae) on lipid peroxidation and free radical scavenging activity.  Phytother Res. 2004;  18 84-86
    CrossrefPubMedSearch in Google Scholar
  • 3 Candan F. Effect of Rhus coriaria L. (Anacardiaceae) on superoxide radical scavenging and xanthine oxidase activity.  J Enzyme Inhib Med Chem. 2003;  18 59-62
    CrossrefPubMedSearch in Google Scholar
  • 4 Zalacain A, Alonso G L, Prodanov M, Carmona M. Determination of the tanning capacity of a Rhus coriaria L. extract and its antioxidant activity.  J Soc Leath Technol Chem. 2000;  84 212-215
    PubMedSearch in Google Scholar
  • 5 Erdèlyi K, Kiss A, Bakondi E, Bai P, Szabo C, Gergely P, Erdődi V. Gallotannin inhibits the expression of chemokines ad inflammatory cytokines in A549 cells.  Mol Pharmacol. 2005;  68 895-904
    PubMedSearch in Google Scholar
  • 6 Maffei Facino R, Carini M, Aldini G, Berti F, Rossoni G, Bombardelli E, Morazzoni P. Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: antioxidant intervention and/or iron and copper sequestering ability.  Planta Med. 1996;  62 495-502
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Legssyuer A, Ziyyat A, Mekhfi H, Bnouham M, Herrenknecht C, Rouny V, Fourneau C, Laurens A, Hoerter J, Fischmeister R. Tannins and cathechin gallate mediate the vasorelaxant effect of Arbutus unedo on the rat isolated aorta.  Phytother Res. 2004;  18 889-894
    CrossrefPubMedSearch in Google Scholar
  • 8 Singleton V L, Orthofer R, Lamuela-Raventos R M. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent.  Meth Enzymol. 1999;  299 152-178
    PubMedSearch in Google Scholar
  • 9 Brand-Williams W, Cuvelier M E, Berset C. Use of a free radical method to evaluate antioxidant activity.  Lebensm Wiss Technol. 1995;  28 25-30
    CrossrefPubMedSearch in Google Scholar
  • 10 Carini M, Aldini G, Bombardelli E, Morazzoni P, Maffei Facino R. UVB-induced hemolysis of rat erythrocytes: protective effect of procyanidins from grape seeds.  Life Sci. 2000;  67 1799-1814
    CrossrefPubMedSearch in Google Scholar
  • 11 Rossoni G, Sparatore A, Tazzari V, Manfredi B, Del Soldato P, Berti F. The hydrogen sulphide-releasing derivative of diclofenac protects against ischaemia-reperfusion injury in the isolated rabbit heart.  Br J Pharmacol. 2008;  53 100-109
    PubMedSearch in Google Scholar
  • 12 Henry P D, Schuchleib R, Davis J, Weiss E S, Sobel B E. Myocardial contracture and accumulation of mitochondrial calcium in ischemic rabbit heart.  Am J Physiol. 1977;  233 H677-H684
    PubMedSearch in Google Scholar
  • 13 Rossoni G, Berti F, Bernareggi M, Villa L, Agozzino S, Cereda R, Giuliani P, Mizrahi J. Protective effects of ITF 296 in the isolated rabbit heart subjected to global ischemia.  J Cardiovasc Pharmacol. 1995;  26 S44-S52
    PubMedSearch in Google Scholar
  • 14 Bergmeyer H U, Rich W, Butter H, Schmidt E, Hillman G, Kreuz F H, Stamm D, Lang H, Szasz G, Laue D. Standardization of methods for estimation of enzyme activity in biological fluids.  Z Klin Chem Klin Biochem. 1970;  8 658-660
    PubMedSearch in Google Scholar
  • 15 Hohorst H J. L-(+)-lactate. Bergmeyer HU Methods of enzymatic analysis. New York; Academic Press 1963: 215-219
    Search in Google Scholar
  • 16 Pradelles P, Grassi J, Maclouf J. Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: an alternative to radioimmunoassay.  Anal Chem. 1985;  57 1170-1173
    CrossrefPubMedSearch in Google Scholar
  • 17 Gurevitch J, Frolkis I, Yuhas Y, Paz Y, Matsa M, Mohr R, Yakirevich V. Tumor necrosis factor-alpha is released from the isolated heart undergoing ischemia and reperfusion.  J Am Coll Cardiol. 1996;  28 247-252
    CrossrefPubMedSearch in Google Scholar
  • 18 Rossoni G, Berti F, Trento F, Cattaneo F, Porta R, Pescador R, Ferro L. Defibrotide normalizes cardiovascular function hampered by established atherosclerosis in the rabbit.  Thromb Res. 2000;  97 29-38
    CrossrefPubMedSearch in Google Scholar
  • 19 Rossoni G, Grande S, Galli C, Visioli F. Wild artichoke prevents the age-associated loss of vasomotor function.  J Agric Food Chem. 2005;  53 10291-10296
    CrossrefPubMedSearch in Google Scholar
  • 20 Fong H S, Bhatti W, Farnsworth N R. Antitumor activity of certain plants due to tannins.  J Pharm Sci. 1972;  61 1818
    CrossrefPubMedSearch in Google Scholar
  • 21 Mota M L, Thomas G, Barbosa Filho J M. Anti-inflammatory actions of tannins isolated from the bark of Anacardium occidentale L.  J Ethnopharmacol. 1985;  13 289-300
    CrossrefPubMedSearch in Google Scholar
  • 22 Uchiumi F, Sato T, Tanuma S. Identification and characterization of a tannic acid-responsive negative regulatory element in the mouse mammary tumor virus promoter.  J Biol Chem. 1998;  273 12499-12508
    CrossrefPubMedSearch in Google Scholar
  • 23 Van Molle W, Van den Berghe J, Brouckaert P, Libert C. Tumor necrosis factor-induced lethal hepatitis: pharmacological intervention with verapamil, tannic acid, picotamide, and K76COOH.  FEBS Lett. 2000;  467 201-205
    CrossrefPubMedSearch in Google Scholar
  • 24 Feldman K S, Sahasrabudhe K, Lawlor M D, Wilson S L, Lang C H, Scheuchenzuber W J. In vitro and in vivo inhibition of LPS-stimulated tumor necrosis factor-alpha secretion by the gallotannin beta-D-pentagalloylglucose.  Bioorg Med Chem Lett. 2001;  11 1813-1815
    CrossrefPubMedSearch in Google Scholar
  • 25 Buzzini P, Arapitsas P, Goretti M, Branda E, Turchetti B, Pinelli P, Ieri F, Romani A. Antimicrobial and antiviral activity of hydrolysable tannins.  Mini Rev Med Chem. 2008;  8 1179-1187
    CrossrefPubMedSearch in Google Scholar
  • 26 Hu H, Lee H J, Jiang C, Zhang J, Wang L, Zhao Y, Xiang Q, Lee E O, Kim S H, Lü J. Penta-1,2,3,4,6-O-galloyl-beta-D-glucose induces p 53 and inhibits STAT3 in prostate cancer cells in vitro and suppresses prostate xenograft tumor growth in vivo.  Mol Cancer Ther. 2008;  7 2681-2691 , Erratum in: Mol Cancer Ther. 2008;  7 3654
    CrossrefPubMedSearch in Google Scholar
  • 27 Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E–deficient mice.  Am J Clin Nutr. 2000;  71 1062-1076
    PubMedSearch in Google Scholar
  • 28 Widlansky M E, Hamburg N M, Anter E, Holbrook M, Kahn D F, Elliott J G, Keaney J F, Vita J A. Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary hearth disease.  J Am Coll Nutr. 2007;  26 95-102
    PubMedSearch in Google Scholar
  • 29 Stoclet J C, Chataigneau T, Ndiaye M, Oak M, El-Bedoui J, Chataigneau M, Schini-Kerth V B. Vascular protection by dietary polyphenols.  Eur J Pharmacol. 2004;  400 299-313
    PubMedSearch in Google Scholar

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

    www.thieme-connect.de/ejournals/toc/plantamedica