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Article: Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs

TitleAcacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs
Authors
KeywordsArrhythmia
Drugs
Electrophysiology
Ion channels
Pharmacology
Issue Date2008
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.org
Citation
Circulation, 2008, v. 117 n. 19, p. 2449-2457 How to Cite?
AbstractBACKGROUND - 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 (IKur) 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 μmol/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 Ca 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. © 2008 American Heart Association, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/77012
ISSN
2015 Impact Factor: 17.047
2015 SCImago Journal Rankings: 7.853
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, GRen_HK
dc.contributor.authorWang, HBen_HK
dc.contributor.authorQin, GWen_HK
dc.contributor.authorJin, MWen_HK
dc.contributor.authorTang, Qen_HK
dc.contributor.authorSun, HYen_HK
dc.contributor.authorDu, XLen_HK
dc.contributor.authorDeng, XLen_HK
dc.contributor.authorZhang, XHen_HK
dc.contributor.authorChen, JBen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorXu, XHen_HK
dc.contributor.authorCheng, LCen_HK
dc.contributor.authorChiu, SWen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorLau, CPen_HK
dc.date.accessioned2010-09-06T07:27:19Z-
dc.date.available2010-09-06T07:27:19Z-
dc.date.issued2008en_HK
dc.identifier.citationCirculation, 2008, v. 117 n. 19, p. 2449-2457en_HK
dc.identifier.issn0009-7322en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77012-
dc.description.abstractBACKGROUND - 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 (IKur) 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 μmol/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 Ca 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. © 2008 American Heart Association, Inc.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.orgen_HK
dc.relation.ispartofCirculationen_HK
dc.rightsCirculation. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subjectArrhythmiaen_HK
dc.subjectDrugsen_HK
dc.subjectElectrophysiologyen_HK
dc.subjectIon channelsen_HK
dc.subjectPharmacologyen_HK
dc.subject.meshAction Potentials - drug effectsen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAnti-Arrhythmia Agents - pharmacologyen_HK
dc.subject.meshAtrial Fibrillation - drug therapy - prevention & controlen_HK
dc.subject.meshAtrial Function - drug effectsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshFlavones - pharmacology - therapeutic useen_HK
dc.subject.meshGuinea Pigsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMedicine, Chinese Traditionalen_HK
dc.subject.meshMyocytes, Cardiacen_HK
dc.subject.meshPatch-Clamp Techniquesen_HK
dc.subject.meshPotassium - metabolismen_HK
dc.titleAcacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0009-7322&volume=117&issue=19&spage=2449&epage=57&date=2008&atitle=Acacetin,+a+natural+flavone,+selectively+inhibits+human+atrial+repolarization+potassium+currents+and+prevents+atrial+fibrillation+in+dogs.en_HK
dc.identifier.emailLi, GR: grli@hkucc.hku.hken_HK
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1161/CIRCULATIONAHA.108.769554en_HK
dc.identifier.pmid18458165-
dc.identifier.scopuseid_2-s2.0-43449090419en_HK
dc.identifier.hkuros146209en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-43449090419&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume117en_HK
dc.identifier.issue19en_HK
dc.identifier.spage2449en_HK
dc.identifier.epage2457en_HK
dc.identifier.eissn1524-4539-
dc.identifier.isiWOS:000255776700005-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001120731-
dc.identifier.scopusauthoridLi, GR=7408462932en_HK
dc.identifier.scopusauthoridWang, HB=35216701200en_HK
dc.identifier.scopusauthoridQin, GW=7202860696en_HK
dc.identifier.scopusauthoridJin, MW=35932258500en_HK
dc.identifier.scopusauthoridTang, Q=40861778800en_HK
dc.identifier.scopusauthoridSun, HY=35723049200en_HK
dc.identifier.scopusauthoridDu, XL=9036718000en_HK
dc.identifier.scopusauthoridDeng, XL=14057894600en_HK
dc.identifier.scopusauthoridZhang, XH=37092287700en_HK
dc.identifier.scopusauthoridChen, JB=8692691800en_HK
dc.identifier.scopusauthoridChen, L=25652992200en_HK
dc.identifier.scopusauthoridXu, XH=37082609600en_HK
dc.identifier.scopusauthoridCheng, LC=9533935800en_HK
dc.identifier.scopusauthoridChiu, SW=12788356600en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK

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