Atherosclerosis remains a great threat to human health worldwide. Previous studies found that tetramethylpyrazine (TMP) and paeoniflorin (PF) combination (TMP-PF) exerts anti-atherosclerotic effects in vitro. However, whether TMP-PF improves atherosclerosis in vivo needs further exploration. The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^-/- mice and explore the related molecule mechanisms. Results showed that TMP and high-dose TMP-PF decreased serum TG and LDL-C levels, suppressed VEGFR2 and NR4A1 expression in aortic tissues, inhibited plaque angiogenesis, reduced plaque areas, and alleviated atherosclerosis in ApoE^-/- mice. Also, TMP-PF exhibited a better modulation effect than TMP or PF alone. However, NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF. In conclusion, TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway, indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease. Extra virgin olive oil (EVOO) is the typical sources of fat in the Mediterranean diet which have been shown to have noteworthy nutritional value and positive impact on human health. It is worth noting that EVOO owes its superior nutritional value to its bioactive composition. The main component of EVOO is monounsaturated fatty acids (MUFAs) in the form of oleic acid. Oleic acid accounts for up to 70%‒80% of EVOO. Secondly, EVOO contains approximately more than 30 phenolic compounds, of which HT is essential for the protection against cardiovascular diseases. In this review, we focused on the potential mechanisms of oleic acid and polyphenols combat cardiovascular diseases risk in terms of oxidative stress, inflammation, blood pressure, endothelial function and cholesterol. This review might provide a reference for the studies on cardiovascular protective effects of EVOO.