Bin Leng1, Futian Tang2, Meili Lu2, Zhen Zhang2, Hongxin Wang3, Yingjie Zhang4. 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.
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.
Authors: Lin Zhang; Chenfei Li; Liting Yang; Gabriel Komla Adzika; Jeremiah Ong'achwa Machuki; Mingjin Shi; Qi Sun; Hong Sun Journal: Front Cardiovasc Med Date: 2021-06-16
Authors: Bin Tang; Hang Hong Lo; Cheng Lei; Ka In U; Wen-Luan Wendy Hsiao; Xiaoling Guo; Jun Bai; Vincent Kam-Wai Wong; Betty Yuen-Kwan Law Journal: Phytomedicine Date: 2020-03-18 Impact factor: 5.340
Authors: Bin Leng; Cong Li; Yang Sun; Kun Zhao; Ling Zhang; Mei-Li Lu; Hong-Xin Wang Journal: Oxid Med Cell Longev Date: 2020-09-14 Impact factor: 6.543