title: Cardiovascular effects in vitro of aqueous extract of wild strawberry (Fragaria vesca, L.) leaves.
abstract: In contrast to the strawberry fruits, strawberry leaves as a source of bioactive compounds with potentially beneficial biological effects have been largely overlooked. In this study we examined direct, dose-dependent effects of wild strawberry (Fragaria vesca, L.) leaves aqueous extract, in two experimental models and animal species, the isolated guinea pig hearts and rat aortic rings. Vasodilatory potential of the wild strawberry leaves extract was compared with vasodilatory activity of aqueous extract of hawthorn (Crataegus oxycantha, L) leaves with flowers, which can be regarded as a reference plant extract with a marked vasodilatory activity. The extracts were analysed by their "phenolic fingerprints", total phenolic content and antioxidative capacity. Their vasodilatory activity was determined and compared in the isolated aortic rings from 24 rats that were exposed to the extracts doses of 0.06, 0.6, 6, and 60 mg/100ml. Both extracts induced similar, dose-dependent vasodilation. Maximal relaxation was 72.2+/-4.4% and 81.3+/-4.5%, induced by the strawberry and hawthorn extract, respectively. To determine vasodilatory mechanisms of the wild strawberry leaves extract, endothelium-denuded and intact rings exposed to nitric oxide (NO) synthase inhibitor L-NAME or cyclooxygenase inhibitor indomethacin were used. Removal of the endothelium prevented and exposure to L-NAME or indomethacin strongly diminished the vasodilatatory response to the extract. In the isolated hearts (n=12), the wild strawberry extract was applied at concentrations of 0.06, 0.18, 0.6, and 1.8 mg/100ml. Each dose was perfused for 3.5 min with 15 min of washout periods. Heart contractility, electrophysiological activity, coronary flow and oxygen consumption were continuously monitored. The extract did not significantly affect heart rate and contractility, main parameters of the cardiac action that determine oxygen demands, while coronary flow increased up to 45% over control value with a simultaneous decrease of oxygen extraction by 34%. The results indicate that the aqueous extract of wild strawberry leaves is a direct, endothelium-dependent vasodilator, action of which is mediated by NO and cyclooxygenase products and which potency is similar to that of the hawthorn aqueous extract.
authors.affiliation: Department of Pharmacology, University of Split School of Medicine, Split, Croatia.
authors.forename: I
authors.initials: I
authors.lastname: Mudnic
authors.forename: D
authors.initials: D
authors.lastname: Modun
authors.forename: I
authors.initials: I
authors.lastname: Brizic
authors.forename: J
authors.initials: J
authors.lastname: Vukovic
authors.forename: I
authors.initials: I
authors.lastname: Generalic
authors.forename: V
authors.initials: V
authors.lastname: Katalinic
authors.forename: T
authors.initials: T
authors.lastname: Bilusic
authors.forename: I
authors.initials: I
authors.lastname: Ljubenkov
authors.forename: M
authors.initials: M
authors.lastname: Boban
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D027825:Crataegus; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology; D031985:Fragaria / Q000737:chemistry*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000032:analysis / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D014665:Vasodilator Agents; D009569:Nitric Oxide