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Synthesis and Anti-hepatic Fibrosis Activity of Novel Matrine Tricyclic Derivatives

Yongchuang Wang, Hang Yang, Wenming Tang, Luozhu Zhou, Chuanhao Wang, Anhua Huang, Daozuan Zhang, Zheng Yao, Wei Li, Wannian Zhang, Yuelin Wu, Weiheng Xu, Zhenyuan Miao

Abstract

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 protein level. Molecular docking disclosed that compound ZM842 maybe inhibit the activation of HSCs in a direct interaction mode 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.

CH24160  Accepted 30 March 2025

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