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: 2.4). 01/2009; 24(6):875-84. DOI: 10.1002/ptr.3038
Source: PubMed

ABSTRACT 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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    ABSTRACT: This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB. Copyright © 2014 John Wiley & Sons, Ltd.
    Phytotherapy Research 11/2014; 29(2). DOI:10.1002/ptr.5254 · 2.40 Impact Factor
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    ABSTRACT: Remissions of nephrotic syndrome due to membranous nephropathy (MN) induced by Astragalus membranaceus have drawn nephrologists attention to medicinal herbs as alternative treatments of glomerulonephritis. MN stands for a group of chronic glomerulonephritides that are routinely treated with corticosteroids and cytotoxic drugs, although treatment responses are unsatisfactory and the toxic burden significant. The investigational status of Astragalus and other medicinal herbs like Angelica sinensis, Tripterygium wilfordii, Rheum palmatum, Ligusticum wallichii, Perilla frutescens, Salvia miltiorrhiza, Arctium lappa with respect to their use as treatments of chronic renal disease and specifically of glomerulonephritis is reviewed. Most of these herbs are in current clinical use in China and appear to have promising constituents capable of modifying immune processes in glomerulonephritis. Nevertheless, their application in patients can still not be advocated as clinical studies meeting international quality standards have not been performed and toxic risks had not been excluded with adequate scrutiny.
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    ABSTRACT: Astragalus membranaceus (astragalus), originally described in the Shennong’s Classic of Materia Medica two thousand years ago, is used as a Qi-tonifying herb in traditional Chinese medicine. It is an important ingredient in many herbal formulas used to treat a variety of symptoms and ailments including fatigue and rectal prolapse. The root of astragalus is rich in saponins and polysaccharides. Modern research suggests antioxidant, immunomodulatory, and cytostatic properties. Animal and anecdotal human data show that astragalus reduces immunosuppression, a side effect of chemotherapy and it may also enhance the effects of such treatments. Whereas oral and parenteral preparations have been developed in Asia, products containing astragalus are consumed as dietary supplements in the West. Several formulas containing astragalus have been studied in cancer patients. Data indicate that they are safe to use in conjunction with chemotherapy and reduce treatment associated adverse effects. Based on existing evidence, there is also substantial interest in developing astragalus-based preparations for certain cancers. Although all products studied to date contain astragalus as the main ingredient, the variation across formulas makes it difficult to draw definitive conclusions. Future studies should address this issue. Astragalus is generally considered safe for traditional use, but the potential for herb-drug interactions exists because botanicals contain biologically active compounds. This chapter presents information about the use of astragalus in traditional medicine and summarizes existing scientific evidence of its benefits and limitations as an adjuvant cancer treatment.
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