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山竹提取物对血管内皮细胞活化生物标志物的抑制作用。

Inhibitory effects of Syzygium jambos extract on biomarkers of endothelial cell activation.

机构信息

Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.

Department of Biochemistry and Pharmacology, San Juan Bautista School of Medicine, PO Box 4968, Caguas, PR, 00726-4968, USA.

出版信息

BMC Complement Med Ther. 2022 Apr 7;22(1):101. doi: 10.1186/s12906-022-03572-7.

Abstract

BACKGROUND

Disordered endothelial cell activation plays an important role in the pathophysiology of atherosclerosis, cancer, sepsis, viral infections, and inflammatory responses. There is interest in developing novel therapeutics to regulate endothelial cell function in atherothrombotic, metabolic, vascular, and hematological diseases. Extracts from leaves of the Syzygium jambos (L.) Alston (S. jambos) trees have been proposed to treat cardiovascular diseases and diabetes through unclear mechanisms. We investigated the effects of the S. jambos extract on biomarkers of endothelial dysfunction and immune responses in the human endothelial cell line, EA.hy926.

METHODS

Leaves of S. jambos were collected, concocted and lyophilized. To study the effects of S. jambos on endothelial cell activation, we used the human endothelial cell line. IL-6 levels were measured using qPCR and ELISA. PDI activity was measured using Insulin Turbidity and Di-E-GSSG assays. CM-H2DCFDA was used to study ROS levels. Migration assay was used to study S. jambos effect on ex vivo human polymorphonuclear and human mononuclear cells.

RESULTS

Our results show that incubation of EA.hy926 cells with ET-1 led to a 6.5 ± 1.6 fold increase in IL-6 expression by qPCR, an event that was blocked by S. jambos. Also, we observed that ET-1 increased extracellular protein disulfide isomerase (PDI) activity that was likewise dose-dependently blocked by S. jambos (IC = 14 μg/mL). Consistent with these observations, ET-1 stimulated ex vivo human polymorphonuclear and mononuclear cell migration that also was dose-dependently blocked by S. jambos. In addition, ET-1 stimulation led to significant increases in ROS production that were sensitive to S. jambos.

CONCLUSION

Our results suggest that the S. jambos extract represents a novel cardiovascular protective pharmacological approach to regulate endothelial cell activation, IL-6 expression, and immune-cell responses.

摘要

背景

内皮细胞功能紊乱在动脉粥样硬化、癌症、脓毒症、病毒感染和炎症反应的病理生理学中起着重要作用。人们有兴趣开发新型治疗方法来调节动脉血栓形成、代谢、血管和血液疾病中的内皮细胞功能。从 Syzygium jambos (L.) Alston 树叶中提取的提取物被提议通过不明确的机制来治疗心血管疾病和糖尿病。我们研究了 S. jambos 提取物对人内皮细胞系 EA.hy926 中内皮功能障碍和免疫反应生物标志物的影响。

方法

收集、炮制和冻干 S. jambos 的叶子。为了研究 S. jambos 对内皮细胞激活的影响,我们使用人内皮细胞系。使用 qPCR 和 ELISA 测量 IL-6 水平。使用胰岛素浊度和 Di-E-GSSG 测定法测量 PDI 活性。使用 CM-H2DCFDA 研究 ROS 水平。迁移实验用于研究 S. jambos 对离体人多形核细胞和人单核细胞的影响。

结果

我们的结果表明,用 ET-1 孵育 EA.hy926 细胞导致 IL-6 表达增加了 6.5±1.6 倍,这一事件被 S. jambos 阻断。此外,我们观察到 ET-1 增加了细胞外蛋白二硫键异构酶(PDI)的活性,这也被 S. jambos 呈剂量依赖性阻断(IC=14μg/mL)。与这些观察结果一致,ET-1 刺激离体人多形核细胞和单核细胞迁移,这也被 S. jambos 呈剂量依赖性阻断。此外,ET-1 刺激导致 ROS 产生显著增加,这对 S. jambos 敏感。

结论

我们的结果表明,S. jambos 提取物代表了一种调节内皮细胞激活、IL-6 表达和免疫细胞反应的新型心血管保护药理学方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/8991810/ea64de2c39bf/12906_2022_3572_Fig1_HTML.jpg

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