1. Astragaloside IV improves vascular endothelial dysfunction by inhibiting the TLR4/NF-κB signaling pathway.
- Author
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Leng, Bin, Tang, Futian, Lu, Meili, Zhang, Zhen, Wang, Hongxin, and Zhang, Yingjie
- Subjects
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VASCULAR endothelial cells , *ASTRAGALUS membranaceus , *ANTIOXIDANT analysis , *STREPTOZOTOCIN , *INTERLEUKIN-6 - Abstract
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. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]
- Published
- 2018
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