Astragaloside IV ameliorates renal fibrosis via the inhibition of mitogen-activated protein kinases and antiapoptosis in vivo and in vitro.

Abstract

Apoptosis of renal tubular cells plays a crucial role in renal fibrosis. Astragaloside IV (AS-IV), a compound extracted from Radix Astragali, has been shown to inhibit renal tubular cell apoptosis induced by high glucose, but its role in preventing chronic renal fibrosis as well as the underlying molecular mechanisms involved still remain obscure. In this study, human kidney tubular epithelial cells induced by transforming growth factor-β1 (TGF-β1) were used to investigate the protective role of AS-IV in antifibrosis. As an in vivo model, mice subjected to unilateral ureteral obstruction (UUO) were administered AS-IV (20 mg/kg) by intraperitoneal injection for 7 days. AS-IV significantly alleviated renal mass loss and reduced the expression of α-smooth muscle actin, fibronectin, and collagen IV both in vitro and in vivo, suggesting that this compound functions in the inhibition of renal tubulointerstitial fibrosis. Furthermore, transferase-mediated dUTP nick-end labeling assay results both in vivo and in vitro showed that AS-IV significantly attenuated both UUO and TGF-β1-induced cell apoptosis and prevented renal tubular epithelial cell injury in a dose-dependent manner. Western blotting results also revealed that the antiapoptotic effect of AS-IV was reflected in the inhibition of caspase-3 activation, which might be mediated primarily by the downregulation of mitogen-activated protein kinase effectors phospho-p38 and phospho-c-Jun N-terminal kinase. These data infer that AS-IV effectively attenuates the progression of renal fibrosis after UUO injury and may have a promising clinical role as a potential antifibrosis treatment in patients with chronic kidney disease.

• Authors: Weijia Xu, Xinghua Shao, Lei Tian, Leyi Gu, Minfang Zhang, Qin Wang, Bei Wu, Ling Wang, Jufang Yao, Xiaoping Xu, Shan Mou, Zhaohui Ni
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 350 Issue 3 Pg. 552-62 (Sep 2014) ISSN: 1521-0103 [Electronic] United States
• PMID: 24951279 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Chemical References

• Protein Kinase Inhibitors
• Saponins
• Triterpenes
• astragaloside A
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Fibrosis (drug therapy, enzymology, pathology)
• Humans
• Kidney Diseases (drug therapy, enzymology, pathology)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Saponins (pharmacology, therapeutic use)
• Triterpenes (pharmacology, therapeutic use)