Kang Dae Gill, Yin Ming Hao, Oh Hyuncheol, Lee Dae Ho, Lee Ho Sub
Department of Herbal Resources, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
Planta Med. 2004 Aug;70(8):718-22. doi: 10.1055/s-2004-827201.
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
在对药用植物各种提取物的血管舒张作用进行体外筛选的过程中，发现卷柏的乙酸乙酯可溶提取物具有显著的血管舒张活性。以体外血管舒张试验为指导，对该提取物进行进一步纯化，得到了一种活性双黄酮——穗花杉双黄酮。穗花杉双黄酮可诱导去氧肾上腺素预收缩的主动脉产生浓度依赖性舒张，去除功能性内皮后这种舒张作用消失。用N(G)-硝基-L-精氨酸甲酯（L-NAME）、亚甲蓝或1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）预处理主动脉组织可抑制穗花杉双黄酮诱导的舒张。加入四乙铵（TEA）或维拉帕米也可显著减弱穗花杉双黄酮诱导的舒张作用。然而，吲哚美辛、格列本脲、阿托品或普萘洛尔预处理并不能阻断穗花杉双黄酮的舒张作用。用穗花杉双黄酮孵育完整内皮的主动脉环可增加cGMP的生成，但这种作用可被内皮剥脱或L-NAME或ODQ预处理所阻断。这些结果表明，穗花杉双黄酮通过内皮依赖性一氧化氮-cGMP信号通路使血管平滑肌舒张，可能涉及非特异性钾（K(+)）和钙（Ca(2+)）通道。缩写词：EDRF：内皮源性舒张因子；EDHF：内皮源性超极化因子；NO：一氧化氮；cGMP：鸟苷3',5'-环一磷酸；DMSO：二甲基亚砜；L-NAME：N(G)-硝基-L-精氨酸甲酯；ODQ：1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮；IBMX：3-异丁基-1-甲基黄嘌呤；K(Ca)：钙（Ca(2+)）依赖性钾（K(+)）通道；K(ATP)：三磷酸腺苷（ATP）敏感性钾（K(+)）通道；TEA：四乙铵
