In vitro electrocardiographic and cardiac ion channel effects of (-)-epigallocatechin-3-gallate, the main catechin of green tea.
Epigallocatechin-3-gallate (EGCG) is the major catechin found in green tea. EGCG is also available for consumption in the form of concentrated over-the-counter nutritional supplements. This compound is currently undergoing clinical trials for the treatment of a number of diseases including multiple sclerosis, and a variety of cancers. To date, few data exist regarding the effects of EGCG on the electrophysiology of the heart. Therefore, we examined the effects of EGCG on the electrocardiogram recorded from Langendorff-perfused guinea pig hearts and on cardiac ion channels using patch-clamp electrophysiology. EGCG had no significant effects on the electrocardiogram at concentrations of 3 and 10 microM. At 30 microM, EGCG prolonged PR and QRS intervals, slightly shortened the QT interval, and altered the shape of the ST-T-wave segment. The ST segment merged with the upstroke of the T wave, and we noted a prolongation in the time from the peak of the T wave until the end. Patch-clamp studies identified the KvLQT1/minK K(+) channel as a target for EGCG (IC(50) = 30.1 microM). In addition, EGCG inhibited the cloned human cardiac Na(+) channel Na(v)1.5 in a voltage-dependent fashion. The L-type Ca(2+) channel was inhibited by 20.8% at 30 microM, whereas the human ether-a-go-go-related gene and Kv4.3 cardiac K(+) channels were less sensitive to inhibition by EGCG. ECGC has a number of electrophysiological effects in the heart, and these effects may have clinical significance when multigram doses of this compound are used in human clinical trials or through self-ingestion of large amounts of over-the-counter products enriched in EGCG.
Kang
Jiesheng
J
Disposition, Safety, and Animal Research, Sanofi-Aventis US Inc., Bridgewater, New Jersey 08807, USA.
Cheng
Hsien
H
Ji
Junzhi
J
Incardona
Josephine
J
Rampe
David
D
D000818:Animals; D016466:CHO Cells; D020746:Calcium Channels, L-Type / Q000502:physiology; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004562:Electrocardiography; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D013237:Stereoisomerism; D013662:Tea
D020746:Calcium Channels, L-Type; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate