RESEARCH ARTICLE Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-b1 production from macrophages in mice Deyong CHU 1* , MD, Conglei LI 1* , BM, Qiang WU 2 , MD, Jilong SHEN (*) 1 , MD, PhD 1 Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases, Anhui Medical University, Hefei 230032, China 2 Department of Pathology, Anhui Medical University, Hefei 230032, China E Higher Education Press and Springer-Verlag 2008 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 treat- ment and both therapeutics were given simultaneously at different time points after the infection. The concentra- tion of serum hyaluronic acid (HA) was determined by radioimmunoassay (RIA). Hepatic granuloma and fib- rosis were evaluated via HE and Masson staining. The expression of a-smooth muscle actin (a-SMA), transform- ing growth factor b1 (TGF-b1) and collagen I (Col I) protein was detected by immunohistochemistry. The effect of soluble egg antigen (SEA) and PAE on the pro- duction of TGF-b1 from mouse peritoneal macrophages (PMQs) was investigated by RT-PCR, Western blotting and ELISA. The effect of TGF-b1 in optimum macro- phage-conditioned medium (OPMCM) on the prolifera- tion of hepatic stellate cells (HSCs) and collagen secretion from HSCs with anti-TGF-b1 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 a-SMA, TGF-b1 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-b1 could be secreted from PMQs stimulated by SEA. Meanwhile, the production of TGF-b1 from PMQs could be depressed significantly by PAE in a con- centration-dependent manner. TGF-b1 could promote the proliferation of HSCs and the secretion of collagens. In a word, PAE can prevent hepatic granuloma and fib- rosis caused by schistosomiasis japonica through the inhibition of the secretion of TGF-b1 from PMQs, the proliferation and activation of HSCs and the secretion of collagens from HSCs. Keywords paeoniflorin; Schistosomiasis japonica; liver cirrhosis; transforming growth factor b1; macrophages; hepatic stellate cell 1 Introduction The egg granulomas and secondary hepatic fibrosis are the primary causes of death in schistosomiasis. Studies have shown that granulomatous inflammatory reaction and fibrosis in the liver tissue continued to aggravate, even though efficacious schistosomicides were given [1–3]. The intervention and control of such aggravation during or before the formation of granuloma or at the early stage of fibrosis formation becomes another key therapeutic strategy after efficacious treatment with praziquantel (PZQ). At present, however, no anti-fibrosis drug with low toxicity and high efficiency has been applied to pre- vent or reverse the hepatic fibrosis in schistosomiasis. The hepatosplenic schistosomiasis is characterized by granulomatous inflammatory response and fibrosis evoked by soluble egg antigen (SEA) which is secreted from eggs of Schistosoma japonicum [4]. Hepatic stellate cells (HSCs) play a pivotal role in hepatic fibrosis of human schistoso- miasis [5,6]. Fibrogenic cytokines, such as transforming growth factor beta 1 (TGF-b1), can activate HSCs to fibro- genic myofibroblasts-like cells that produce much of the excess collagen I (Col I) and III in schistosomiasis [7,8]. Meanwhile, the fibrogenic myofibroblasts-like cells express Received December 13, 2007; accepted January 2, 2008 * Equally contributed to this work E-mail: jlshen@ahmu.edu.cn Front. Med. China 2008, 2(2): 154–165 DOI 10.1007/s11684-008-0029-7