Tetramethylpyrazine Protects against Hydrogen Peroxide‐Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases

Abstract

Background and Objectives. Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP), the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong), prevents endothelial dysfunction in a rat model of oxidative stress. Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2). Changes in isometric tension were then measured in acetylcholine- (ACh-) relaxed rings. Endothelial nitric oxide synthase (eNOS) expression was evaluated in the rings by Western blotting, and superoxide anion (O2 ∙−) content was assessed in primary rat aortic endothelial cells by dihydroethidium- (DHE-) mediated fluorescence microscopy. Results. ACh-induced endothelium-dependent relaxation (EDR) was disrupted by H2O2 in endothelium-intact aortic rings. H2O2-impaired relaxation was ameliorated by acute pretreatment with low concentrations of TMP, as well as by pretreatment with catalase and the NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI). TMP, apocynin, and DPI also reduced O2 ∙− accumulation in endothelial cells,but TMP failed to alter eNOS expression in aortic rings incubated with H2O2. Conclusions. TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. However, TMP's role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation.

Tetramethylpyrazine suppresses lipid accumulation in macrophages via upregulation of the ATP-binding cassette transporters and downregulation of scavenger receptors

“…The in vivo study revealed that atherosclerotic progression in ApoE -/mice was retarded by TMP, which is conformable to a previous study (20). Indeed, TMP exhibited some beneficial effects on atherosclerosis such as preventing endothelial dysfunction (19), regulating lipid levels in the plasma (20), attenuating oxidative stress (21), and inhibiting inflammation (22). In the present study, we further found that TMP decreased the expression of CD36 and SR-A and increased the expression of ABCA1 and ABCG1 in TMP-treated ApoE -/mice.…”

“…Tetramethylpyrazine (TMP) has been recognized as a protective agent against atherosclerosis (19)(20)(21)(22). However, the effect and underlying mechanism by which TMP regulated lipid accumulation in macrophage-derived foam cells remained to be investigated.…”

“…However, it has been reported that TMP was effective in the treatment of a few cardiovascular complications, including angina pectoris and cerebrovascular and thrombotic vascular diseases (15)(16)(17), as a result of its biological activities including vasodilation (17) and antiplatelet aggregation (18). Additionally, TMP exerts anti-atherosclerotic effects via inhibition of endothelial dysfunction (19), regulation of lipid levels in the plasma (20), attenuation of oxidative stress (21) and inflammation (22). However, the effects and molecular mechanisms involved in TMP-mediated lipid accumulation in macrophage-derived foam cells have not been well…”

Natural Drugs as a Treatment Strategy for Cardiovascular Disease through the Regulation of Oxidative Stress

“…Recent studies show that TMP could relieve vascular tension and counteract oxidative stress by scavenging ROS, downregulating ERK1/MAPK signaling, and inhibiting NF- κ B. TMP can also protect vascular endothelial cells from H 2 O 2 -induced injury by increasing the content of phosphatidylcholine, reducing the release of arachidonic acid, and inhibiting the phosphorylation of cytosolic phospholipase A [ 143 , 144 ]. TMP, as an NADPH oxidase inhibitor and ROS scavenger, may be a potential antioxidant drug for the treatment of heart failure [ 145 ].…”

Role and mechanism of nursing cooperation and tetramethylpyrazine application in post‑operative pain in patients undergoing total knee arthroplasty

“…Tetramethylpyrazine (TMP) is an alkaloid monomer that exists in the roots or stems of the Chinese herbal medicine, Ligusticum wallichii (9). Previous studies have reported that TMP primarily acts as an antioxidant, calcium antagonist, inhibitor of platelet aggregation, promoter of microcirculation and blood clots, and regulator of the immune response (10,11).…”