Vasorelaxation by amentoflavone isolated from Selaginella tamariscina.
In the courses of in vitro screening for the vasorelaxant effect of the various extracts from medicinal plants, an ethyl acetate-soluble extract of Selaginella tamariscina was found to exhibit distinctive vasorelaxant activity. Further purifications of the extract as guided by in vitro vasorelaxant assay afforded an active biflavonoid, amentoflavone. Amentoflavone induced concentration-dependent relaxation of the phenylephrine-precontracted aorta, which disappeared by removal of functional endothelium. Pretreatment of the aortic tissues with N(G)-nitro- L-arginine methyl ester (L-NAME), methylene blue, or 1 H- -oxadiazolo[4,3- a]quinoxalin-1-one (ODQ) inhibited the relaxation induced by amentoflavone. Amentoflavone-induced relaxations were also markedly attenuated by addition of tetraethylammonium (TEA) or verapamil. However, the relaxant effect of amentoflavone was not blocked by pretreatment with indomethacin, glibenclamide, atropine, or propranolol. Incubation of endothelium-intact aortic rings with amentoflavone increased the production of cGMP, but this effect was blocked by endothelium-denudation or pretreatment with L-NAME or ODQ. These results suggest that amentoflavone relaxes vascular smooth muscle via endothelium-dependent nitric oxide-cGMP signaling, with possible involvement of non-specific K (+) and Ca (2+) channels. Abbreviations. EDRF:endothelium-derived relaxing factor EDHF:endothelium-derived hyperpolarizing factor NO:nitric oxide cGMP:guanosine 3',5'-cyclic monophosphate DMSO:dimethyl sulfoxide L-NAME: N(G)-nitro- L-arginine methyl ester ODQ:1 H-[1,2,4]-oxadiazole-[4,3- a]-quinoxalin-1-one IBMX:3-isobutyl-1-methylxanthine K (Ca):Ca (2+)-dependent K (+) channel K (ATP):adenosine triphosphate (ATP)-sensitive K (+) channel TEA:tetraethylammonium
Kang
Dae Gill
DG
Department of Herbal Resources, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
Yin
Ming Hao
MH
Oh
Hyuncheol
H
Lee
Dae Ho
DH
Lee
Ho Sub
HS
D000818:Animals; D001011:Aorta / Q000187:drug effects; D044946:Biflavonoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D008751:Methylene Blue; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D010069:Oxadiazoles; D010656:Phenylephrine; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D032503:Selaginellaceae
C116907:1H-(1,2,4)oxadiazolo(4,3-a)-quiloxalin-1-one; D044946:Biflavonoids; D010069:Oxadiazoles; D010936:Plant Extracts; D010656:Phenylephrine; C011164:amentoflavone; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester