Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation
Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation
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灯盏乙素可防止血管内皮功能障碍，并通过抗氧化预防动脉粥样硬化
DOI：
10.1016/j.phymed.2018.03.021
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发表时间：
2018-03-15
期刊：
影响因子：
7.9
通讯作者：
Shen, Zhiqiang
中科院分区：
文献类型：
--
作者：
Mo, Jiao;Yang, Renhua;Shen, Zhiqiang
背景：灯盏乙素是灯盏细辛临床疗效的主要成分之一。Mazz在传统中药中发现了悠久的民族药理用途。灯盏乙素作为一种纯化合物，目前正在研究其对各种组织损伤的保护作用。目的：观察灯盏乙素对氧化应激诱导的血管内皮细胞功能障碍和内皮细胞损伤的影响，进而评价灯盏乙素预防大鼠动脉粥样硬化的疗效。观察灯盏乙素对1，1-二苯基-2-苦基肼(DPPH)刺激的兔胸主动脉环内皮依赖性松弛(EDR)的影响。观察灯盏乙素对H_2O_2损伤的人脐静脉内皮细胞(HUVECs)活性、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)活性及SOD1和NADPH氧化酶4(NOX4)表达的影响。结果：灯盏乙素在体外具有较强的抗氧化活性。灯盏乙素预处理保留了DPPH损伤兔胸主动脉环的EDR。在H_2O_2损伤的HUVECs中，灯盏乙素逆转了ROS水平和抗氧化酶活性的有害变化，并恢复了SOD1和NOX4的mRNA和蛋白表达。灯盏乙素可剂量依赖地改善高脂血症大鼠的高脂血症，减轻大鼠血清中的氧化应激，与参比药物阿托伐他汀的作用相似。结论：灯盏乙素在体外对氧化应激诱导的血管内皮功能障碍和内皮细胞损伤具有保护作用，在体内可能通过抗氧化作用预防动脉粥样硬化。这一结果为灯盏乙素在心血管疾病中的临床应用提供了进一步的研究依据。
Background: Scutellarin is the major constituent responsible for the clinical benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure compound is now under investigation for its protections against various tissue injuries.Purpose: This study aims to examine the effects of scutellarin on oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage, and then to evaluate the therapeutic efficacy of scutellarin in preventing atherosclerosis in rats.Methods: Radical scavenging ability of scutellarin was determined in vitro. Impact of scutellarin on endothelium-dependent relaxation (EDR) of rabbit thoracic aortic rings upon 1, 1-diphenyl-2-picrylhydrazyl (DPPH) challenge was measured. Influences of scutellarin pre-treatment on the levels of reactive oxygen species (ROS), activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase and catalase, and the expression of SOD1 and NADPH oxidase 4 (Nox4) in human umbilical vein endothelial cells (HUVECs) injured by H2O2 were examined. Anti-atherosclerotic effect of scutellarin was evaluated in rats fed with high fat diet (HFD).Results: Scutellarin showed potent antioxidant activity in vitro. Pretreatment of scutellarin retained the EDR of rabbit thoracic aortic rings damaged by DPPH. In H2O2 injured-HUVECs the deleterious alterations in ROS levels and antioxidant enzymes activity were reversed by scutellarin and the mRNA and protein expression of SOD1 and Nox4 were restored also. Oral administration of scutellarin dose-dependently ameliorated hyperlipidemia in HFD-fed rats and alleviated oxidative stress in rat serum, mimicking the effects of reference drug atorvastatin.Conclusion: Scutellarin protects against oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage in vitro and prevents atherosclerosis in vivo through antioxidation. The results rationalize further investigation into the clinical use of scutellarin in cardiovascular diseases.