Therapeutic potential of EGCG in treating vascular and metabolic disorders

Vascular and metabolic diseases, including atherosclerosis, aortic aneurysm and dissection, obesity, type 2 diabetes, and metabolic dysfunction–associated steatotic liver disease (MASLD), constitute a major global health burden and share common pathogenic features driven by metabolic stress and chronic low-grade inflammation. (−)-Epigallocatechin-3-gallate (EGCG), a dietary polyphenol and the most abundant catechin in green tea, has attracted sustained attention because of its pleiotropic biological activities in both vascular and metabolic settings. Traditional mechanistic interpretations have primarily focused on its antioxidant capacity and suppression of inflammatory signaling; however, these classical pathways do not fully explain the context and stage dependent effects observed across different disease models. Emerging evidence indicates that EGCG also acts on upstream regulatory programs, including mitochondrial stress signaling, mtDNA–cGAS–STING activation, inflammasome signaling, pyroptosis, ferroptosis, cellular senescence, epitranscriptomic regulation such as the m6A/FTO axis, and gut–organ metabolic crosstalk. These pathways provide a unifying framework linking the actions of EGCG across vascular tissues, adipose depots, pancreatic islets, and the liver. In addition, synergistic interactions between EGCG and other compounds, such as caffeine, may enhance its bioactivity. Although EGCG appears promising as a dietary bioactive compound, its low bioavailability, interindividual variability, and potential dose-related adverse effects, particularly hepatotoxicity at high supplemental doses, should be carefully considered in future translational and clinical studies.