Effect of Astragalus membranaceus and Angelica sinensis combined with Enalapril in rats with obstructive uropathy.
ACE inhibitors (ACEi) reduce renal tubulointerstitial fibrosis but are not completely effective. Combined extract of Astragalus membranaceus and Angelica sinensis (A&A) is a traditional antifibrotic agent in China. The present investigation aimed to determine whether an ACEi (Enalapril) and A&A together have a better antifibrotic effect in unilateral ureteral obstruction (UUO) than monotherapy with either agent. Male Sprague-Dawley rats (N = 4 per group) had either sham operation or UUO alone, with A&A (combined aqueous and ethanol extract equivalent to 2.1 g dried herbs), with Enalapril (in drinking water at 200 mg/mL) or with both treatments. Kidney and liver were collected for protein extraction or fixed for histologic stains, immunohistochemistry (IHC), microscopy. Enalapril or A&A individually were antifibrotic. Transforming growth factor-beta1, fibroblast activation, collagen deposition, macrophage accumulation and tubular cell apoptosis were all decreased. The combination of the two drugs was significantly more effective than Enalapril alone in reducing tumor necrosis factor-alpha, collagen accumulation, activation of fibroblasts, and tubular cell apoptosis. In conclusion, Enalapril with A&A significantly decreased tubulointerstitial fibrosis to a greater extent than treatment with Enalapril alone. Further studies focusing on the isolation of the active constituents of A&A and the clinical application of the combination of ACEi plus A&A are warranted to determine the value of this treatment in humans.
Wojcikowski
Ken
K
Molecular and Cellular Pathology, School of Medicine, University of Queensland, Brisbane, Queensland, Australia. kwojciko@scu.edu.au
Wohlmuth
Hans
H
Johnson
David W
DW
Gobe
Glenda
G
D029971:Angelica sinensis / Q000737:chemistry*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D027885:Astragalus propinquus / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D004656:Enalapril / Q000627:therapeutic use*; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014517:Ureteral Obstruction / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D004656:Enalapril; D003094:Collagen