Epigallocatechin-3-gallate and zinc provide anti-apoptotic protection against hypoxia/reoxygenation injury in H9c2 rat cardiac myoblast cells

Abstract

It has previously been demonstrated that phospha-tidylinositol-3-kinase (PI3K)/Akt and cleaved caspase-3 serve critical roles in the apoptosis of cardiac myocytes following ischemia/reperfusion injury. Epigallocatechin-3-gallate (EGCG), the predominant catechin component of green tea, has been reported to have potential cardioprotective effects in primary cultures of cardiac myocytes exposed to I/R injury, mediated through inhibition of signal transducers and activators of transcription-1 activity. In addition, it is also known that the biological behavior of EGCG may be influenced by metal ions, for example the hepatoprotective activity of EGCG has been reported to be enhanced by zinc. In the present study, the protective effects of EGCG with zinc were assessed on cultures of rat cardiac myoblasts exposed to hypoxia/reoxygenation (H/R) injury. H9c2 cells were subjected to 3-h hypoxia, followed by 1-h reperfusion. EGCG and/or zinc were perfused prior to induced hypoxic stress. It was demonstrated that when EGCG interacted with zinc, the anti-apoptotic activity was significantly enhanced. To the best of our knowledge, the current study was the first to demonstrate that EGCG + Zn2+ protects H9c2 cells against H/R injury through activation of the PI3K/Akt pathway, as determined by western blotting. Since EGCG + Zn2+ may, at least in part, protect cardiac myocytes against H/R-induced apoptotic cell death, the PI3K/Akt pathway of EGCG may be enhanced by its interactions with zinc during H/R injury. Furthermore, it was suggested that a similar procedure may be implemented in a clinical setting, in order to maximize PI3K/Akt activation levels in patients with acute coronary artery disease. EGCG and zinc may therefore represent effective agents for use in the prevention of I/R injury in clinical practice.

Pure Polyphenols Applications for Cardiac Health and Disease

“…In addition, I/R is known to trigger oxidative stress and massive cell death during the reperfusion phase. In various cellular models, EGCG proved to have anti-apoptotic properties via the activation of phosphoinositide 3-kinase/protein kinase-B (PI3K/Akt )pathway [63] or via the phosphorylation of signal transducer and activator of transcription 1 (Stat1), known lays a critical role in the induction of cardiomyocyte apoptosis [64]. Nevertheless, depending on the dose, micromolar vs nonamolar range, EGCG can become toxic by acting on ATPsensitive potassium (KATP) channels [65].…”

Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release

“…To date, EGCG has been demonstrated to be an anticancer [ 13 , 14 , 15 ], antioxidant, and antibacterial [ 16 ] agent, and also chemopreventive, anti-inflammatory, and anti-aging in topical treatments [ 17 ]. It is also reported to be protective against cardiovascular [ 18 , 19 , 20 ] and neurodegenerative diseases [ 21 , 22 ], UV-induced photodamage, basal cell carcinomas, melanomas, skin papillomas [ 23 , 24 ], obesity, and diabetes [ 2 ]. In addition, EGCG has shown interactions with a number of proteins such as α-synuclein, amyloid-β, and huntingtin, with a redirection to non-toxic species or remodeling of fibrils [ 25 ].…”

Epigallocatechin gallate attenuates overload-induced cardiac ECM remodeling via restoring T cell homeostasis

“…Green tea was used to treat various diseases in the traditional Chinese medicine. Later people realized that Epigallocatechin gallate (EGCG) is the major catechin in green tea and is regarded to have strong antioxidant activity, which may prevent cell damage, exert numerous protective effects on cancer growth, hyperlipidemia, diabetes, stroke, particularly on the cardiovascular system (7)(8)(9). Green tea consumers have lower death risk from cardiovascular diseases.…”