Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial fibrosis in chronic iron-overloaded mice.

Abstract

Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen), a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old) were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp) quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and protein expression levels of type I collagen (COL I), type I collagen (COL III), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative stress.

• Authors: Ying Zhang, Hao Wang, Lijing Cui, Yuanyuan Zhang, Yang Liu, Xi Chu, Zhenyi Liu, Jianping Zhang, Li Chu
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0124061 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25850001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Collagen Type III
• Drugs, Chinese Herbal
• Plant Extracts
• Transforming Growth Factor beta1
• dan-shen root extract
• Malondialdehyde
• Iron-Dextran Complex
• Verapamil
• Iron
• Superoxide Dismutase
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse
• Deferoxamine

Topics

• Animals
• Collagen Type I (metabolism)
• Collagen Type III (metabolism)
• Deferoxamine (therapeutic use)
• Drugs, Chinese Herbal (therapeutic use)
• Endomyocardial Fibrosis (drug therapy)
• Iron (metabolism)
• Iron Overload (drug therapy, pathology)
• Iron-Dextran Complex (administration & dosage)
• Malondialdehyde (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Medicine, Chinese Traditional
• Mice
• Oxidative Stress (drug effects)
• Plant Extracts
• Random Allocation
• Salvia miltiorrhiza (metabolism)
• Superoxide Dismutase (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Verapamil (therapeutic use)