TA is a plant-derived polyphenol that has been of great interest for many years. Polyphenolic compounds as important plant-derived dietary components have antioxidant and/or free radical-scavenging properties in vitro and play an important role in the prevention of coronary artery disease29. Among many studies, extracts from plants were most used. Choi group showed that 0.02% dietary TA has health-promoting effects by alleviating hepatic lipogenesis and atherogenesis in ApoE −/− mice through increasing liver peroxisome proliferator-activated receptor α (PPARα) expression19. In our study, we show that the vasoprotective effects of TA is mediated through activating KLF2, which provide mechanistic insights into vascular benefits of TA. Multiple factors and signaling pathways are involved in the regulation of KLF2 including shear stress, statins, phosphoinositide-3-kinase (PI3K)-dependent/Akt independent pathway and AMPK-dependent MEK5/ERK5/MEF2 signaling pathway7, 30, 31. Jain group has demonstrated that statins induced KLF2 luciferase activity via MEF2 binding site21. In this study, using KLF2 -221 WT and KLF2 -221 mutant plasmids, we found that simvastatin indeed induced KLF2 expression totally dependent on MEF2 binding site. Compared with simvastatin, TA also significantly increased KLF2 expression through MEF2. In addition, we observed that TA increased ERK5 phosphorylation. Therefore, it is likely that TA induced KLF2 expression in part through the ERK5/MEF2 pathway. Further studies are needed to prove the involvement of MEK5/ERK5/MEF2 in TA-induced KLF2 expression and anti-inflammatory effect. In addition, it warrants further investigation to see whether there are some other mechanisms including AMPK activation act synergistically in the process of TA-induced KLF2 expression.