Antispasmodic effect of selected Citrus flavonoids on rat isolated jejunum specimens

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• 作者：Marta Mendel ; ^{marta_mendel@sggw.pl" class="auth_mail" title="E-mail the corresponding author} ; Magdalena Chłopecka ; Natalia Dziekan ; Wojciech Karlik
• 关键词：4-aminopyridine (PubChem CID ; 1727) ; 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) ; Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) (PubChem CID ; 39836) ; tetraethylammonium (PubChem CID ; 5413)
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：791
• 期：Complete
• 页码：640-646
• 全文大小：713 K

文摘

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 (10–100 µM) and reversibly inhibited acetylcholine (1 µM) and KCl (80 mM) induced contractile activity. The antispasmodic effect of hesperetin was partially blocked by 4-aminopyridine (100 µM), glibenclamide (100 µM) and NG-nitro-L-arginine methyl ester (L-NAME, 100 µM). By contrast, apamin (0.1 µM), tetraethylammonium (500 µM) and methylene blue (10 µM) did not affect the magnitude of hesperetin-induced myorelaxant effect. Indomethacin (10 µM) 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.