Astragaloside IV protects against hyperglycemia-induced vascular endothelial dysfunction by inhibiting oxidative stress and Calpain-1 activation.

Abstract

AIMS:

Vascular endothelial cells act as a selective barrier between circulating blood and vessel wall and play an important role in the occurrence and development of cardiovascular diseases. Astragaloside IV (As-IV) has a protective effect on vascular endothelial cells, but its underlying mechanism remains unclear. This study is aimed at investigating the effect of As-IV on endothelial dysfunction (ED).

METHODS:

Male Sprague-Dawley (SD) were injected intraperitoneally with 65 mg/kg streptozotocin (STZ) to induce diabetes and then administered orally with As-IV (40, 80 mg/kg) for 8 weeks. Vascular function was evaluated by vascular reactivity in vivo and in vitro. The expression of calpain-1 and eNOS in the aorta of diabetic rats was examined by western blot. NO production was measured using nitrate reductase method. Oxidative stress was determined by measuring SOD, GSH-px and ROS.

RESULTS:

Our results showed that As-IV administration significantly improved diabetes associated ED in vivo, and both NAC (an antioxidant) and MDL-28170 (calpain-1 inhibitor) significantly attenuated hyperglycemia-induced ED in vitro. Meanwhile, pretreatment with the inhibitor l-NAME nearly abolished vasodilation to ACh in all groups of rats. Furthermore, As-IV increased NO production and the expression of eNOS in the thoracic aorta of diabetic rats. In addition, the levels of ROS were significantly increased, and the activity of SOD and GSH-px were decreased in diabetic rats, while As-IV administration reversed this change in a concentration-dependent manner.

CONCLUSION:

These results suggest that As-IV improves endothelial dysfunction in thoracic aortas from diabetic rats by reducing oxidative stress and calpain-1.

• Authors: Qu Nie, Liping Zhu, Lijie Zhang, Bin Leng, Hongxin Wang
• Journal: Life sciences (Life Sci) Vol. 232 Pg. 116662 (Sep 01 2019) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31323271 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Biomarkers
• Cysteine Proteinase Inhibitors
• Dipeptides
• Saponins
• Triterpenes
• Nitric Oxide
• astragaloside A
• Streptozocin
• Nitric Oxide Synthase Type III
• Calpain
• Capn1 protein, rat
• calpain inhibitor III
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Aorta, Thoracic (drug effects, metabolism)
• Biomarkers (metabolism)
• Calpain (metabolism)
• Cysteine Proteinase Inhibitors (pharmacology)
• Diabetes Mellitus, Experimental (metabolism)
• Dipeptides (pharmacology)
• Endothelium, Vascular (drug effects, metabolism, pathology)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hyperglycemia (metabolism, pathology)
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Saponins (pharmacology)
• Streptozocin
• Triterpenes (pharmacology)
• Vasodilation (drug effects)