In Vitro Electrocardiographic and Cardiac Ion Channel Effects of (−)-Epigallocatechin-3-Gallate, the Main Catechin of Green Tea

Abstract

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 M. At 30 M, 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 ϩ channel as a target for EGCG (IC 50 ϭ 30.1 M). In addition, EGCG inhibited the cloned human cardiac Na ϩ channel Na v 1.5 in a voltage-dependent fashion. The L-type Ca 2ϩ channel was inhibited by 20.8% at 30 M, whereas the human ether-a-gogo-related gene and Kv4.3 cardiac K ϩ 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.Green tea, prepared from the leaves of Camellia sinensis, is a popular beverage that is purported to have a number of beneficial health effects including antithrombotic, anti-inflammatory, and anticancer activities (Higdon and Frei, 2003;Wolfram, 2007;Clement, 2009). Green tea is rich in polyphenolic compounds known as catechins, and these catechins are believed to be responsible for the physiological activity of green tea and its extracts. The major catechin found in green tea is epigallocatechin-3-gallate (EGCG) (Fig. 1), which constitutes approximately 65% of the total catechins found in green tea (Balentine et al., 1997). On average, brewed green tea provides 78 mg of EGCG per cup (U.S. Department of Agriculture database for the flavonoid content of selected foods, release 2.1, http://www.nal.usda. gov/fnic/foodcomp/data/flav/flav.html). EGCG is also available for consumption in the form of concentrated extracts of green tea sold as over-the-counter nutritional supplements containing up to 200 to 400 mg of ECGC per dose.These concentrated preparations are used both as dietary supplements and in controlled human clinical trials (see http://www.clinicaltrials.gov).A number of studies have examined the effects of EGCG on various biochemical pathways (Beltz et al., 2006;Chen et al., 2008;Tachibana, 2009). However, relatively few studies have been conducted to assess its effects on voltage-dependent ion chann...

Coordinated Regulation of Murine Cardiomyocyte Contractility by Nanomolar (−)-Epigallocatechin-3-Gallate, the Major Green Tea Catechin

“…At these pharmacological concentrations, the actions of EGCG are mediated by selective activation of ryanodine receptor type 2 (RyR2) and inhibition of plasmalemma Ca 2ϩ fluxes via the Na ϩ -Ca 2ϩ exchanger (NCX), with negligible influence on Ca 2ϩ -ATPase (SERCA2), Na ϩ -H ϩ exchanger, and Na ϩ -K ϩ -ATPase. Previous work has shown that nanomolar EGCG has also no effect on L-type Ca 2ϩ current in ventricular myocytes (Kang et al, 2010). These coordinated actions of EGCG result in a net shift of Ca 2ϩ transport during the cardiac cycle away from the plasma membrane to the energetically more favorable sarcoplasmic reticulum (SR) Ca 2ϩ transport, which may represent a novel therapeutic strategy for increasing cardiac contractility in patients with heart failure.…”

“…It is therefore likely that results from in vitro experiments at high concentrations could mask more specific mechanisms by which EGCG exerts its biological actions at pharmacologically relevant doses (Ͻ10 M). Recent reports suggest that EGCG increases cardiac contractility at low micromolar concentrations (1-5 M) (Lorenz et al, 2008) without altering ECG parameters and cardiac ion channels (Kang et al, 2010). The molecular mechanisms responsible for the positive inotropic effect of EGCG remain unclear.…”

Natural Flavonoids in StAR Gene Expression and Testosterone Biosynthesis in Leydig Cell Aging

“…For example, calcium influx through L-type calcium channels regulates the threshold of cAMP-induced StAR gene expression, so that blocking the L-type calcium channels reduced the threshold and enhanced StAR gene expression in Leydig cells (Pandey et al, 2010). There is a group of natural flavonoids that are able to block the L-type calcium channels, such as genistein (Belevych et al, 2002), daidzein (Yokoshiki et al, 1996), equol (Liew et al, 2003) and epigallocatechin-3-gallate (EGCG) (Kang et al, 2010). The steroidogenic effects of the flavonoids in this group were described (Yu et al, 2010).…”

Effects of green tea epigallocatechin-3-gallate on the proteolipid protein and oligodendrocyte transcription factor 1 messenger RNA gene expression in a mouse model of multiple sclerosis

“…The interest in polyphenols is related to their well-known antioxidant activities which are reported to have positive effects on human health, due to their presence in dietary sources such as fruits, vegetables, wine, spices and herbs [16]. Green tea, prepared from the leaves of Camellia sinensis, is one of the popular beverages that are reported to have a number of beneficial health effects, including anti-inflammatory, anti-thrombotic and anticancer activities [12]. Green tea is rich in polyphenolic compounds, known as catechins, that are responsible for the physiological activity of green tea and its extracts.…”