Synthesis and anti-hepatic fibrosis activity of novel matrine tricyclic derivatives

Matrine, a component derived from traditional Chinese medicine, exhibits diverse pharmacological effects such as anti-hepatic fibrosis. Here we have investigated novel matrine tricyclic derivatives designed by a molecular fusion strategy for anti-fibrotic effects. Among these new compounds, ZM842 indicated potent inhibitory TGF-β transcriptional activity in a dose-dependent manner by a TGF-β/Smads reported gene assay. TGF-β1-stimulated LX-2 cells were treated with compound ZM842, resulting in a reduction of fibrosis markers, including collagen I and α-SMA, as observed at the protein level. Molecular docking disclosed that compound ZM842 may inhibit the activation of hepatic stellate cells (HSCs) by directly interacting with TGF-β1 and SMAD-3 proteins. In summary, our results suggest that compound ZM842 inhibits the TGF-β1 signaling pathway and HSC activation, indicating its potential as an anti-hepatic fibrosis agent.