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.
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.
Beretta
Giangiacomo
G
Department of Pharmaceutical Sciences Pietro Pratesi, University of Milan, Via Mangiagalli 25, 20133 Milan, Italy. giangiacomo.beretta@unimi.it
Rossoni
Giuseppe
G
Santagati
Natale Alfredo
NA
Facino
Roberto Maffei
RM
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic; D001713:Biphenyl Compounds / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D006321:Heart; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007213:Indomethacin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000378:metabolism; D008517:Phytotherapy; D010851:Picrates / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D029045:Rhus / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000975:Antioxidants; D001713:Biphenyl Compounds; D047348:Hydrolyzable Tannins; D010069:Oxadiazoles; D010851:Picrates; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D015121:6-Ketoprostaglandin F1 alpha; C004931:1,1-diphenyl-2-picrylhydrazyl; D007770:L-Lactate Dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases; D003402:Creatine Kinase; D009638:Norepinephrine; D007213:Indomethacin