Astragaloside attenuates cardiotoxicity effects of Doxorubicin by inhibiting TLR4/NF-кB signaling pathway

Russell Nahorski; Arnim Ploeger; Lorena Ludovici; Raffaele Marchis; Stephen Eikan; Maria Mckay; Fiorella Gille; Detlef Mazzon 

AJBM  Volume 2, Issue 4, pages 463–479, April 2014             Full Text-PDF


Doxorubicin (DOX) is one of the most widely used and successful antitumor drugs, but its cumulative and dose-dependent cardiac toxicity has been the major concern of oncologists in cancer therapeutic practice for decades. Cardiotoxicity is a major limiting factor in anticancer therapy. Astragaloside (Ast) is one of the main effective components isolated from the traditional Chinese medical herb Astragalus membranaceus. The possible protective effects Ast against cardiotoxicity were investigated in wild type C57BL/6 mice treated with saline, saline+doxorubicin (DOX; 20 mg/kg) or Ast (20 mg/kg)+DOX continued for a period of 5 weeks. The cardiomyopathy was assessed using transthoracic echocardiography before the start of treatment and after 14 days and plasma lactate dehydrogenase (LDH) activity was measured after 14 days. Cardiac catheterizations for assessments LV function before the mice were decapitated. To measure the transverse diameter of left ventricular myocardial cells (TDM), the hematoxylin-eosin (HE) staining method was applied. In addition, the volume and the total protein content of cardiomyocytes were measured, the mRNA expression of ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4, IκBα and p65 were quantified by Western blot, and the level of TNF-α and IL-6 were measured by ELISA. Ast treatment demonstrated improved LV function, TDM were significantly decreased; the protein expression of TLR4 and p65 were reduced, while the IκBα were increased; the expression of ANP, TLR4 mRNA, and TNF-α, IL-6 in serum were significantly reduced compared with the doxorubicin-treated group. The study suggests that Ast may have a potential protective role against doxorubicin-induced cardiotoxicity in mice.

Keywords: Astragaloside; Cardiomyopathy; Doxorubicin; Chemotherapy, Cardiotoxicity


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