EGCG targeting autophagy in cardiovascular diseases: mechanisms and therapeutic potential.

Green tea is abundant in natural polyphenols and has become one of the most popular healthy non-alcoholic beverages worldwide. Epigallocatechin-3-gallate (EGCG), the major catechin identified in green tea, has been shown to protect against cardiovascular diseases (CVDs). Autophagy degrades damaged or superfluous cellular components. Accumulating in vivo and in vitro studies have indicated that dysregulation of autophagy is implicated in the progression of CVDs. Notably, EGCG exerts a context‑dependent bidirectional modulation of autophagy in CVDs, restoring protective autophagy when it is deficient in conditions such as diabetic cardiomyopathy, and suppressing excessive autophagic flux when it is overactivated in conditions such as myocardial ischemia/reperfusion injury. Emerging studies suggest that EGCG regulates autophagic activity in CVDs through multiple signaling pathways, such as mTOR, SIRT, FoxO, miRNA, and ERK. Notably, most of the available evidence is derived from preclinical studies, and direct clinical evidence supporting EGCG as a therapeutic agent targeting autophagy in humans remains limited. Furthermore, there is an urgent need to address the issues of oral bioavailability and the gap in clinical translation for EGCG. This review comprehensively summarizes the role of EGCG in targeting autophagy and elucidates the associated signaling mechanisms in CVDs, thereby offering systematic insights to guide future research.