Effects of tanshinone IIA on fibrosis in a rat model of cirrhosis through heme oxygenase-1, inflammation, oxidative stress and apoptosis.

Tanshinone IIA is extracted from the root of Salvia miltiorrhiza and used in traditional Chinese medicine for its anti-inflammatory activity and antioxidant effects. The aim of the present study was to investigate the potential protective effects of tanshinone IIA against fibrosis in a rat model of cirrhosis and to elucidate the underlying mechanisms. Male Sprague Dawley rats were used as the model of cirrhosis in the present study. In the cirrhotic rats, the extent of fibrosis, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), heme oxygenase­1 (HO­1) protein expression, serum levels of nuclear factor (NF)­κB, tumor necrosis factor­α (TNF­α), interleukin (IL)­1ß and IL­6, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH­PX), and the protein expression levels of phosphorylated­p38 mitogen­activated protein kinase (MAPK) were all significantly increased. However, the serum malondialdehyde (MDA) activity and protein kinase B (Akt) protein expression were suppressed in cirrhotic rats compared with the sham (control) group. Compared with the cirrhotic group, administration of tanshinone IIA reduced the extent of fibrosis, levels of ALT and AST, HO­1 protein expression, serum NF­κB, TNF­α, IL­1ß and IL­6 levels, and the activity of SOD, CAT and GSH­PX. Furthermore, administration of tanshinone IIA significantly increased the inhibition of the serum MDA activity and the Akt protein expression in cirrhotic rats compared with those in the cirrhotic group. The protective effect of tanshinone IIA suppresses fibrosis in a rat model of cirrhosis, and reduces inflammation and oxidative stress, via the HO­1, Akt and p38 MAPK signaling pathway.