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

Abstract

Chuanxiong Rhizoma, the dried rhizome of Ligusticum chuanxiong Hort., is a commonly used drug for promoting blood circulation and dissipating congestion. Tetramethylpyrazine (TMP), the main active ingredient of Ligusticum chuanxiong, 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. In vitro 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. In vivo experiments showed that TMP restored PTK787-induced damage to intersegmental vessels (ISVs) in Tg(fli-1: EGFP)y1 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.

Therapeutic effects and molecular mechanisms of natural products in thrombosis

“…Herba leonuri is widely used in China for the treatment of gynecological diseases, and its characteristic component, leonurine, can inhibit thrombosis by dilating blood vessels, suppressing oxidative stress, platelet activation, and coagulation cascade (Liao et al, 2021). Tetramethylpyrazine is the main active component of Ligusticum chuanxiong , it prevented H 2 O 2 ‐induced endothelial damage in human umbilical vein endothelial cells (HUVECs), restored intersegmental vessel damage and inhibited adrenalin hydrochloride‐induced oxidative damage and thrombosis in zebrafish (Zhang, Ma, et al, 2022). In recent years, several natural products approved by the Food and Drug Administration (FDA) for the treatment of other diseases have been found to have antithrombotic activity.…”

“…adrenalin hydrochloride-induced oxidative damage and thrombosis in zebrafish(Zhang, Ma, et al, 2022). In recent years, several natural products approved by the Food and Drug Administration (FDA) for the treatment of other diseases have been found to have antithrombotic activity.…”

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms

“…TMP can inhibit oxidative stress and protect endothelial cells by regulating the MAPK signalling pathway (Zhang et al, 2020;Zhang, Ma, He, et al, 2022).…”

“…TMP can inhibit the expression of fga, fgb, fgg, f7, and vWFmRNA, exerting an anti‐thrombotic effect. TMP can inhibit oxidative stress and protect endothelial cells by regulating the MAPK signalling pathway (Zhang et al, 2020; Zhang, Ma, He, et al, 2022).…”

Integrating Network Pharmacology And Experimental Verification To Explore The Mechanism Of Qionggui Power Against Atherosclerosis

“…In recent years, several experimental studies have evaluated the cardioprotective effects of QP using modern scientific methods [9] , and these investigations raise the possibility of its application in AS treatment. Although modern pharmacological experiments have suggested various activities associated with the anti-inflammatory, anti-oxidative, and anti-aging effects of QP [10, 11] , the bioactive component and pharmacological mechanism underlying these benefits remain obscure.…”