Smads are intracellular signal transductive molecules of the TGF super family. According to differences in structure and function, nine Smads have been reported and classified into three groups. Smads 2 and 3 are named R Smads in the pathway and Smad4 Co Smads for all these pathways. Smads 6, 7, 8 are inhibitory factors of these Smads. When TGF 1 binds to its receptor, Smad 2 3 is phosphorylated and binds with Smad4 and together they move into the nucleus for translation and expression of the target gene . Smad signal transduction pathways are thought to play a crucial role in the process of liver damage and recovery, as well as liver fibrosis. These transcriptional responses appear to be mediated predominantly through Smad4. The widely held conclusion that Smad4 occupies a central role in transduction of TGF 1 signals comes from multiple lines of biochemical and genetic evidence . In reconstitution experiments, cell lines that lack Smad4 fail to respond to TGF 1 signals, transfection of wildtype Smad4 restores the signaling capabilities of these cells . Our study showed that both mRNA and protein expressions of Smad4 were remarkably up regulated in fibrotic rats.
We also observed down regulation of Smad4 expression Romidepsin in emodin treated fibrotic rats, suggesting that emodin attenuate hepatic fibrosis by regulating TGF 1 smad signaling. In conclusion, the data presented herein provide evidence that emodin is active as an antifibrogenic drug able to reduce the biological effects of TGF 1 in ongoing fibrogenesis. Giant Knotweed Rhizome, a traditional Chinese herbal medicine, is widely used in clinical practice for treating cirrhosis. Emodin, the main active monomer isolated from Giant Knotweed Rhizome, may be an attractive therapeutic agent for the treatment of fibrotic liver diseases. Emodin was purchased from Tianxingjian Bio. Co and was diluted to 5.80 mg mL using dH2O just before administration. APS was purchased from Hongsheng Biotech. Co. and was diluted to 28.80 mg mL in H2O just before administration. Lamivudine was kindly provided by GlaxoSmithKline China Co, and was diluted to 5 mg mL in dH2O.
Animals and drug administration Sixty adult C57 TgN SMMU mice weighing between 18 24 g with an equal number of males and females, were provided by the Laboratory Animal Center and Department chemical library kinase inhibitor of Cell Biology of the Second Military Medical University. The mice were randomly divided into three groups with 20 mice in each group. Group A was the normal control, where the mice were administered physiological saline; group B was the positive control where the mice were administered lamivudine solution . Group C was the experimental group where the mice were administered physiological saline containing emodin and APS . The mice were treated daily for 3 wk followed by one week of recovery time without any treatment.