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Mechanism of protective effects of Danshen against iron overload-induced injury in mice
Authors:Yonggang Gao  Na Wang  Ying Zhang  Zhihong Ma  Peng Guan  Juanjuan Ma  Yuanyuan Zhang  Xuejing Zhang  Jiangyan Wang  Jianping Zhang  Li Chu
Institution:1. Department of Pharmacology, School of Basic Medicine, Hebei Medical University, 326, Xinshi South Road, Shijiazhuang, 050091 Hebei, China;2. The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Hebei Normal University, Shijiazhuang, 050016 Hebei, China;3. Department of Pathology, School of Basic Medicine, Hebei Medical University, 326, Xinshi South Road, Shijiazhuang, 050091 Hebei, China;4. Department of Biochemistry, Bethune Military Medical College, 450, Zhongshan Western Road, Shijiazhuang, 050081 Hebei, China
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, 3 g/kg/day), high-dose Danshen (H-Danshen, 6 g/kg/day) and deferoxamine (DFO) groups (n=12 per group). Iron dextran was injected intraperitoneally (i.p.) at 50 mg/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.
Keywords:ALT  alanine aminotransferase  AST  aspartate aminotransferase  BSA  bovine serum albumin  BW  body weight  CCBs  calcium channel blockers  DFO  deferoxamine  GSH-Px  glutathione peroxidase  H-Danshen  high-dose Danshen  H&  E  hematoxylin and eosin  i  p    intraperitoneally  KM mice  Kunming mice  L-Danshen  low-dose Danshen  MDA  malondialdehyde  SOD  superoxide desmutase  TUNEL  TdT-mediated dUDP nick end labeling
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