Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-β1 production from macrophages in mice

Abstract

In order to investigate the effect of paeoniflorin (PAE) on hepatic fibrosis of mice with Schistosomiasis japonica in vivo and in vitro, a model of hepatic fibrosis caused by schistosomiasis was established in mice infected with cercariae of Schistosoma japonicum. Then, PAE was orally administered before and after praziquantel treatment and both therapeutics were given simultaneously at different time points after the infection. The concentration of serum hyaluronic acid (HA) was determined by radioimmunoassay (RIA). Hepatic granuloma and fibrosis were evaluated via HE and Masson staining. The expression of α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1) and collagen I (Col I) protein was detected by immunohistochemistry. The effect of soluble egg antigen (SEA) and PAE on the production of TGF-β1 from mouse peritoneal macrophages (PMϕs) was investigated by RT-PCR, Western blotting and ELISA. The effect of TGF-β1 in optimum macrophage-conditioned medium (OPMCM) on the proliferation of hepatic stellate cells (HSCs) and collagen secretion from HSCs with anti-TGF-β1 antibody was explored by MTT assay and ELISA. The results show that PAE could significantly reduce the concentration of serum HA, the size of egg granuloma, the severity of hepatic fibrosis and the expression of α-SMA, TGF-β1 and Col I protein in the pre-treatment group. However, in sim-or post-treatment group, PAE did not have any significant therapeutic effect. TGF-β1 could be secreted from PMϕs stimulated by SEA. Meanwhile, the production of TGF-β1 from PMϕs could be depressed significantly by PAE in a concentration-dependent manner. TGF-β1 could promote the proliferation of HSCs and the secretion of collagens. In a word, PAE can prevent hepatic granuloma and fibrosis caused by schistosomiasis japonica through the inhibition of the secretion of TGF-β1 from PMϕs, the proliferation and activation of HSCs and the secretion of collagens from HSCs.