Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase

Aims: Tanshinone IIA is an important ingredient in the herb danshen (Salvia miltiorrhiza), which has been used to treat cardiovascular diseases such as atherosclerosis and angina for hundreds of years in China. There are numerous reports that TIIA has anti-oxidant properties but the chemical structure indicates that TIIA is fully oxidized. Here, we test the hypothesis that TIIA alters the expression and/or activity of specific antioxidation enzymes to protect cells from oxidant damage. Main methods: We utilized J774 macrophages to model cellular responses to TIIA when challenged with H2O2. Expression and activity levels of several anti-oxidation enzymes were investigated and the only system modulated by TIIA was glutathione peroxidase (GPx). Key findings: GPx-1 mRNA levels were significantly increased by TIIA but not the vitamin E analogue, Trolox. GPx activities were also significantly increased by TIIA. Mercaptosuccinic acid inhibited GPx activity and the protective effect of TIIA was attenuated. Thus, TIIA protects cultured macrophages from H2O2-induced cell death and protection is mediated in large part by TIIA induction of GPx gene expression and activity. Significance: Because of the importance of GPx in health and because TIIA is able to modulate GPx activity to some extent in cell culture, we suggest that TIIA is a worthwhile candidate for further study in animal models of atherosclerosis and eventually in human prospective trials. Published by Elsevier Inc.