Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs
文献类型：期刊论文
| 作者 | Li, Gui-Rong2,3; Wang, Hong-Bing1; Qin, Guo-Wei1; Jin, Man-Wen4; Tang, Qiang4; Sun, Hai-Ying3; Du, Xin-Ling; Deng, Xiu-Ling3; Zhang, Xiao-Hua4; Chen, Jing-Bo4 |
| 刊名 | CIRCULATION
 |
| 出版日期 | 2008-05-13 |
| 卷号 | 117期号:19页码:2449-2457 |
| 关键词 | arrhythmia drugs electrophysiology pharmacology ion channels |
| ISSN号 | 0009-7322 |
| DOI | 10.1161/CIRCULATIONAHA.108.769554 |
| 文献子类 | Article |
| 英文摘要 | Background-The development of atrium-selective antiarrhythmic agents is a current strategy for inhibiting atrial fibrillation (AF). The present study investigated whether the natural flavone acacetin from the traditional Chinese medicine Xuelianhua would be an atrium-selective anti-AF agent. Methods and Results-The effects of acacetin on human atrial ultrarapid delayed rectifier K+ current (I-Kur) and other cardiac ionic currents were studied with a whole-cell patch technique. Acacetin suppressed IKur and the transient outward K+ current (IC50 3.2 and 9.2 mu mol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the acetylcholine-activated K+ current; however, it had no effect on the Na+ current, L-type Ca2+ current, or inward-rectifier K+ current in guinea pig cardiac myocytes. Although acacetin caused a weak reduction in the hERG and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, it did not prolong the corrected QT interval in rabbit hearts. In anesthetized dogs, acacetin (5 mg/kg) prolonged the atrial effective refractory period in both the right and left atria 1 to 4 hours after intraduodenal administration without prolongation of the corrected QT interval, whereas sotalol at 5 mg/kg prolonged both the atrial effective refractory period and the corrected QT interval. Acacetin prevented AF induction at doses of 2.5 mg/kg (50%), 5 mg/kg (85.7%), and 10 mg/ kg (85.7%). Sotalol 5 mg/ kg also prevented AF induction (60%). Conclusions-The present study demonstrates that the natural compound acacetin is an atrium- selective agent that prolongs the atrial effective refractory period without prolonging the corrected QT interval and effectively prevents AF in anesthetized dogs after intraduodenal administration. These results indicate that oral acacetin is a promising atrium- selective agent for the treatment of AF. |
| WOS关键词 | CONGESTIVE-HEART-FAILURE ; CELL-CYCLE PROGRESSION ; RECTIFIER K+ CURRENT ; I-KUR ; VENTRICULAR MYOCYTES ; CHANNELS ; BLOCKER ; AVE0118 ; CONTRACTILITY ; MECHANISMS |
| WOS研究方向 | Cardiovascular System & Cardiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000255776700005 |
| 出版者 | LIPPINCOTT WILLIAMS & WILKINS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272917]  |
| 专题 | 天然药物化学研究室 |
| 通讯作者 | Li, Gui-Rong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 2.Univ Hong Kong, Dept Physiol, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China; 3.Univ Hong Kong, Dept Med, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China; 4.Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pharmacol, Wuhan 430074, Peoples R China; 5.Univ Hong Kong, Grantham Hosp, Cardiothorac Unit, Hong Kong, Hong Kong, Peoples R China; 6.Univ Hong Kong, Dept Pharmacol, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Gui-Rong,Wang, Hong-Bing,Qin, Guo-Wei,et al. Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs[J]. CIRCULATION,2008,117(19):2449-2457. |
| APA | Li, Gui-Rong.,Wang, Hong-Bing.,Qin, Guo-Wei.,Jin, Man-Wen.,Tang, Qiang.,...&Lau, Chu-Pak.(2008).Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs.CIRCULATION,117(19),2449-2457. |
| MLA | Li, Gui-Rong,et al."Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs".CIRCULATION 117.19(2008):2449-2457. |
入库方式： OAI收割
来源：上海药物研究所
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