A green tea extract catechin EGCg: Therapeutic potential for pediatric cardiomyopathies

Abstract

Cardiomyopathies comprise a group of disorders wherein the primary defect is in cardiac myocytes. The common forms of pediatric cardiomyopathies, classified according to their morphological and functional manifestations, include dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), hypertrophic cardiomyopathy (HCM), and others. Cardiac gene mutations caused abnormal myofibril Ca²⁺ sensitivity may be involved in the underlying molecular mechanisms of cardiomyopathies. Thus far, no effective treatment for cardiomyopathies has been developed, especially for HCM and RCM in which diastolic dysfunction occurs early and followed by diastolic heart failure. Our laboratory is among the first in the field to investigate the mechanisms underlying various cardiomyopathies and search for the treatment for these disorders. In the past, we and other researchers have found that (-)-epigallocatechin-3-gallate (EGCg), the major biomedical polyphenol extracted from green tea, possess multiple therapeutic effects on protecting cardiac function and correcting impaired relaxation. Given its therapeutic effects, EGCg might be a potential drug candidate for administration to patients with cardiomyopathy and heart failure. In this review, we will discuss the molecular mechanisms associated with the pathogenesis of diastolic dysfunction and summarize the pharmacological effects of EGCg on experimental animals and pediatric patients with cardiomyopathies and diastolic dysfunction.

Keywords: (−)‐epigallocatechin‐3‐gallate; cardiomyopathy; diastolic dysfunction; green tea; heart failure.

FIGURE 1

This figure presents the chemical structure of green tea catechins.

FIGURE 2

This figure summarizes the currently understood mode of actions of EGCg in cardiomyopathy. Mutations in cardiac proteins troponin and tropomyosin, myosin and myosin‐binding protein are the causes of cardiomyopathy. They are the targets of green tea extract EGCg as well. The therapeutic mechanisms of EGCG, focused on balancing myofibril Ca²⁺ sensitivity or recovering the coupled relationship between Ca²⁺ sensitivity and troponin I phosphorylation, for cardiomyopathy and diastolic dysfunction are similar. In contrast, the mechanism of mavacamten is to reduce actin‐myosin cross‐bridge formation.