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Abstract: Ethnopharmacological relevance: Danshen (Salvia miltiorrhiza) has been widely prescribed in traditional folk medicine for treatment of hepatic and cardiovascular diseases in China and other Asian countries for several hundred years. Materials and methods: Sixty male mice were randomly divided into five groups: control, iron overload, low-dose Danshen (L-Danshen, 3g/kg/day), high-dose Danshen (H-Danshen, 6g/kg/day) and deferoxamine (DFO) groups (n=12 per group). Iron dextran was injected intraperitoneally (i.p.) at 50mg/kg body weight/day to establish the iron overload model. While control mice received saline, mice of the treated groups simultaneously received (i.p.) injections of L-Danshen, H-Danshen or DFO daily for 2 weeks. At the end of the experiment, changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), glutathione peroxidase (GSH-Px), superoxide desmutase (SOD) and malondialdehyde (MDA) were measured, and histological changes were observed by Prussian blue or hematoxylin and eosin staining of the liver. Apoptosis was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling. Results: Treatment of iron overloaded mice with either low or high doses of Danshen not only significantly attenuated the hepatic dysfunction (ALT/AST levels), decreased the content of MDA and increased the activities of GSH-Px and SOD, it also suppressed apoptosis in hepatocytes. Histopathological examination showed that treatment with Danshen reduced iron deposition and ameliorated pathological changes in the liver of iron overloaded mice. Conclusions: Danshen demonstrated significant protective effects in the liver of iron overloaded mice, which were at least partly due to the decrease of iron deposition and inhibition of lipid peroxidation and hepatocyte apoptosis. [Copyright &y& Elsevier]