Tetramethylpyrazine Protects Endothelial Injury and Antithrombosis via Antioxidant and Antiapoptosis in HUVECs and Zebrafish

Abstract

Chuanxiong Rhizoma, the dried rhizome of <i>Ligusticum chuanxiong</i> Hort., is a commonly used drug for promoting blood circulation and dissipating congestion. Tetramethylpyrazine (TMP), the main active ingredient of <i>Ligusticum chuanxiong</i>, has significant antioxidant, anti-inflammatory, and vascular protective effects. However, the protective properties and underlying mechanisms of TMP against endothelial injury-induced insufficient angiogenesis and thrombosis have not been elucidated. Therefore, we aimed to explore the protective effects of TMP on endothelial injury and its antithrombotic effects and study the mechanism. <i>In vitro</i> experiments showed that TMP could alleviate hydrogen peroxide- (H₂O₂-) induced endothelial injury of human umbilical vein endothelial cells (HUVECs) and the protective mechanism might be related to the regulation of MAPK signaling pathway, and its antioxidative and antiapoptotic effects. <i>In vivo</i> experiments showed that TMP restored PTK787-induced damage to intersegmental vessels (ISVs) in <i>Tg(fli-1: EGFP)y1</i> transgenic (Flik) zebrafish larvae. Similarly, adrenalin hydrochloride- (AH-) induced reactive oxygen species (ROS) production and thrombosis in AB strain zebrafish were inhibited by TMP. RT-qPCR assay proved that TMP could inhibit the expression of fga, fgb, fgg, f7, and von Willebrand factor (vWF) mRNA to exert an antithrombotic effect. Our findings suggest that TMP can contribute to endothelial injury protection and antithrombosis by modulating MAPK signaling and attenuating oxidative stress and antiapoptosis.