Abstract
Thrombus is considered to be the pathological source of morbidity and mortality of cardiovascular disease and thrombotic complications, while oxidative stress is regarded as an important factor in vascular endothelial injury and thrombus formation. Therefore, antioxidative stress and maintaining the normal function of vascular endothelial cells are greatly significant in regulating vascular tension and maintaining a nonthrombotic environment. Leonurine (LEO) is a unique alkaloid isolated from Leonurus japonicus Houtt (a traditional Chinese medicine (TCM)), which has shown a good effect on promoting blood circulation and removing blood stasis. In this study, we explored the protective effect and action mechanism of LEO on human umbilical vein endothelial cells (HUVECs) after damage by hydrogen peroxide (H2O2). The protective effects of LEO on H2O2-induced HUVECs were determined by measuring the cell viability, cell migration, tube formation, and oxidative biomarkers. The underlying mechanism of antioxidation of LEO was investigated by RT-qPCR and western blotting. Our results showed that LEO treatment promoted cell viability; remarkably downregulated the intracellular generation of reactive oxygen species (ROS), malondialdehyde (MDA) production, and lactate dehydrogenase (LDH); and upregulated the nitric oxide (NO) and superoxide dismutase (SOD) activity in H2O2-induced HUVECs. At the same time, LEO treatment significantly promoted the phosphorylation level of angiogenic protein PI3K, Akt, and eNOS and the expression level of survival factor Bcl2 and decreased the expression level of death factor Bax and caspase3. In conclusion, our findings suggested that LEO can ameliorate the oxidative stress damage and insufficient angiogenesis of HUVECs induced by H2O2 through activating the PI3K/Akt-eNOS signaling pathway.
Highlights
As a chronic multifactorial disease, thrombosis refers to blood clots forming in arteries or veins
The results showed that there was no significant change in cell morphology and no apparent cytotoxicity when treated with LEO at the concentration range of 0.78 μΜ-100 μΜ for 24 h compared with the control group
The significant efficacy of TCM in promoting blood circulation and removing blood clots has been recognized by the majority of patients, such as safflower injection, Danhong injection, and safflower yellow pigment injection
Summary
As a chronic multifactorial disease, thrombosis refers to blood clots forming in arteries or veins. It is considered the pathological phenomenon of cardiovascular disease and thrombotic complications as it often causes myocardial infarction, ischemic stroke, coronary heart disease, acute atherosclerotic syndrome, and pulmonary embolism. The thrombus is seriously threatening people’s life and health [2, 3]. The critical regulator to maintain vascular health and normal function, together with platelets and circulating coagulation proteins, are crucial mediators of thrombosis. Vascular endothelial cells are considered to be the center of vascular diseases as they have anticoagulant, antithrombotic, and plasminogen properties and play an indispensable role in regulating vascular tension and maintaining homeostasis [4].
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