State of the ART: Drug Screening Reveals Artesunate as a Promising Anti-Fibrosis Therapy

Abstract

Fibrosis is a progressive pathological process that severely impairs normal organ function. Current treatments for fibrosis are extremely limited, with no curative approaches available. In a recent article published in Cell, Zhang and colleagues employed drug screening using ACTA2 reporter iPSC-derived cardiac fibroblasts and identified artesunate as a potent antifibrotic drug by targeting MD2/TLR4 signaling. This study provides new insights into strategies for exploiting existing drugs to treat fibrosis.

Keywords: Artesunate; Drug screening; Fibrosis; MD2/TLR4.

Figure 1.

A schematic diagram illustrating the study workflow and the functional pathway of ART in CFs. ACTA2^Clover2 iPSC-CFs were differentiated from ACTA2^Clover2 iPSCs, which were generated using CRISPR-Cas9. Drug screening was conducted following TGF-β1 stimulation and treatment with candidate compounds, leading to the identification of artesunate as a potent antifibrotic drug. Artesunate inhibited MD2/TLR4 signaling activated by DAMPs, thereby suppressing ERK activation—a noncanonical TGF-β pathway—and the subsequent AP-1 pathway, ultimately reducing fibrotic genes transcription and preventing myofibroblast activation. The diagram was generated with BioRender (https://www.biorender.com/).