The relaxation effects of natural polyphenols resveratrol and naringenin on gravid and non-gravid myometrium

[Speaker] Radmila B Novakovic:1
[Co-author] Sanja Cirovic:2, Jasmina Markovic-Lipkovski:2, Nebojsa Radunovic:3, Jovana Rajkovic:1, Vladimir Djokic:1, Helmut Heinle:4, Ljiljana Gojkovic-Bukarica:1
1:Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Serbia, 2:Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 3:Department of Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, Serbia, 4:Institute of Physiology, University of Tuebingen, Tuebingen, Germany

 Natural polyphenols are present in the large number of plant species. As special sources of resveratrol are grapes and wine, as well as its products, but also naringenin grapefruit sort, its juice, hop and beer. During the last decade, resveratrol was in the focus of scientific and wider public as a substance that slows aging, anti-cancer, anti-inflammatory, cardio-protective properties. As a possible site of action is shown by a large number of cellular structures, thus resveratrol is labeled as "one molecule-many targets". Unlike, resveratrol, naringenin belongs to the group being studied less, flavonoids. Its mechanism of inhibition of the contraction of uterine smooth muscle has not been studied. The aims of this study were to investigate the possible inhibitory effect of polyphenols in several experimental models of pregnant and non pregnant uterus.
 The animals used in the experiments were virgin female Wistar rats. Myometrial samples were obtained from nonlaboring women (37-39 weeks gestation) undergoing elective cesarean sections. Samples were mounted into organ bath for recording isometric tension. Resveratrol (1mikroM - 100mikro;M) and naringenin (1mikroM - 1mM) were added cumulatively to the bath for isolated organs. The effects of polyphenols were investigated on the spontaneous rhythmic contractions, oxytocin-induced phasic (0.2nM) and tonic (20nM) contractions of rat uterus and oxytocin-induced (2nM) contractions of human uterus. The effects of synthetic openers of K+ channels, pinacidil and NS16 19 were tested and compared with the effects of polyphenols.
 The results show that resveratrol exerts potent inhibitory effect on the spontaneous and induced contractions of non-pregnant rat uterus and human pregnant myometrium. Naringenin in concentration dependent manner inhibited contraction of animal and human myometrium. Resveratrol showed statistically significantly higher potency of naringenin on all contraction models. Mean effective concentrations of naringenin were similar for all models, which was not the case by the resveratrol.
 : Based on the results presented in this work, it is acceptable to conclude that resveratrol and naringenin have great potential to be used in the prevention and treatment of abnormal and undesirable uterine contractions, as in the case of dysmenorrhea and premature births.

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