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Life Sci. 2018 Sep 15;209:111-121. doi: 10.1016/j.lfs.2018.07.053. Epub 2018 Aug 3.

Astragaloside IV improves vascular endothelial dysfunction by inhibiting the TLR4/NF-κB signaling pathway.

Author information

1
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China; First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
2
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China.
3
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China. Electronic address: hongxinwang@jzmu.edu.cn.
4
First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China. Electronic address: zhangyingjie@jzmu.edu.cn.

Abstract

AIMS:

Astragaloside IV (As-IV) is the major active ingredient of Astragalus membranaceus and has diverse pharmacological activities, including anti-inflammatory and antioxidant effects. However, the beneficial effect of As-IV on protecting vascular endothelial dysfunction is not completely understood. The aim of this study was to investigate the protective effect and mechanism of As-IV on vascular endothelial dysfunction.

MATERIALS AND METHODS:

A diabetes model was established by intraperitoneal injection of streptozotocin (STZ). Endothelial function in isolated aortic rings was examined; serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested by ELISA. The expression of nuclear Factor-κB p65 (NF-κB p65) in aortic tissue was detected by immunohistochemistry. Plasma nitric oxide (NO) was measured by the nitrate reductase method. The expressions of endothelial nitric oxide synthase (eNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and toll-like receptor 4 (TLR4) in aortic tissue were determined by western blot.

KEY FINDINGS:

The results showed that As-IV significantly improved aortic endothelial function; increased eNOS expression and NO production; and decreased the content of IL-6 and TNF-α and the expressions of VCAM-1, ICAM-1, TLR4, and nuclear NF-κB p65 in vitro and in vivo. In addition, the above mentioned effects of As-IV on human umbilical vein endothelial cells (HUVECs) were similar to TAK-242 (TLR4 inhibitor) and Bay 11-7082 (NF-κB p65 inhibitor). Furthermore, L-NAME (NO synthesis inhibitor) partially abolished the effect of As-IV.

SIGNIFICANCE:

As-IV could improve vascular endothelial dysfunction induced by hyperglycemia, and the protective effect of As-IV may be via the TLR4/NF-κB signaling pathway.

KEYWORDS:

Adhesion molecules; Astragaloside IV; Diabetic; Endothelial dysfunction; HUVECs; NF-κB; TLR4

PMID:
30081006
DOI:
10.1016/j.lfs.2018.07.053
[Indexed for MEDLINE]

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