Effect of Astragalus membranaceus and Angelica sinensis combined with Enalapril in rats with obstructive uropathy

Molecular and Cellular Pathology, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Phytotherapy Research (Impact Factor: 2.66). 01/2009; 24(6):875-84. DOI: 10.1002/ptr.3038
Source: PubMed


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.

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    • "Plenty of reports indicate that single compound and extractive deriving from natural products show good therapeutic effects on renal fibrogenesis or renal fibrosis (Wojcikowski et al., 2010; Xie et al., 2010; Yuan et al., 2012). A report shows that increases in α (I)-and α 1 (IV)-collagen, fibronectin, α-SMA, and tissue inhibitors of metalloproteinase 1 mRNA levels, as well as α-SMA and tissue inhibitors of metalloproteinase 1 protein expressions happen in the renal cortex of db/db diabetic mice (Wang et al., 2011). "
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