title: Antispasmodic effect of selected Citrus flavonoids on rat isolated jejunum specimens.
abstract: Citrus flavonoids are acknowledged for numerous pharmacological activities, including the myorelaxant effect on various smooth muscles. However, there is no data on their effect on jejunum contractility. Therefore, the aim of the study at hand was to evaluate the impact of hesperetin and diosmetin along with their glycosides on the motoric activity of intestine and to verify the possible mechanism of hesperetin-induced effect. The experiments were performed on rat isolated jejunum strips and were conducted under isometric conditions. Hesperetin and diosmetin, but not hesperidin and diosmin, dose-dependently (10-100µM) and reversibly inhibited acetylcholine (1µM) and KCl (80mM) induced contractile activity. The antispasmodic effect of hesperetin was partially blocked by 4-aminopyridine (100µM), glibenclamide (100µM) and NG-nitro-L-arginine methyl ester (L-NAME, 100µM). By contrast, apamin (0.1µM), tetraethylammonium (500µM) and methylene blue (10µM) did not affect the magnitude of hesperetin-induced myorelaxant effect. Indomethacin (10µM) increased the force of hesperetin-evoked reaction. In conclusion, hesperetin and diosmetin are potent myorelaxant agents. The antispasmodic effect of hesperetin is partially mediated by fast current low-voltage activated K+channels, voltage-independent K+ channels and involves the nitric oxide pathway. Finally, hesperetin shows a synergistic effect with indomethacin towards jejunal KCl-precontracted smooth muscle.
authors.affiliation: Warsaw University of Life Sciences, Faculty of Veterinary Medicine, Department of Preclinical Sciences, Division of Pharmacology and Toxicology, 8, Ciszewskiego St., 02-786 Warsaw, Poland. Electronic address: marta_mendel@sggw.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Mendel
authors.affiliation: Warsaw University of Life Sciences, Faculty of Veterinary Medicine, Department of Preclinical Sciences, Division of Pharmacology and Toxicology, 8, Ciszewskiego St., 02-786 Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chłopecka
authors.affiliation: Warsaw University of Life Sciences, Faculty of Veterinary Medicine, Department of Preclinical Sciences, Division of Pharmacology and Toxicology, 8, Ciszewskiego St., 02-786 Warsaw, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Dziekan
authors.affiliation: Warsaw University of Life Sciences, Faculty of Veterinary Medicine, Department of Preclinical Sciences, Division of Pharmacology and Toxicology, 8, Ciszewskiego St., 02-786 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Karlik
mesh_terms: D000818:Animals; D002957:Citrus / Q000187:drug effects*; D006569:Hesperidin / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D007583:Jejunum / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013035:Spasm / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D006569:Hesperidin; C013015:hesperetin
keywords: 4-aminopyridine (PubChem CID: 1727); Antispasmodic effect; Diosmetin; Hesperetin; Jejunum; N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) (PubChem CID: 39836); Nitric oxide; Potassium channels; apamin (PubChem CID: 57043712); diosmetin (PubChem CID: 5281612); diosmin (PubChem CID: 5281613); glibenclamide (PubChem CID: 3488); hesperetin (PubChem CID: 72281); hesperidin (PubChem CID: 10621); indomethacin (PubChem CID: 3715); tetraethylammonium (PubChem CID: 5413)