分子影像引导下发现一种用于肝纤维化治疗的有效天然FAPα抑制剂
Molecular imaging-guided discovery of a potent natural FAPα inhibitor for liver fibrosis therapy.
摘要(中文译文)
肝纤维化可进展为肝硬化和肝细胞癌，然而有效的抗纤维化治疗仍然有限。成纤维细胞活化蛋白α（FAPα）是一种有前景的生物标志物和治疗靶点，但现有探针受限于组织穿透性不足和单一模态成像，且有效的FAPα靶向抗纤维化药物仍然缺乏。在此，我们展示Cs-FAP——一种基于半花菁的近红外荧光/光声双模态探针，能够实现对纤维化肝组织中FAPα活性的实时、无创可视化。利用整合高内涵成像和色谱纯化的Cs-FAP引导筛选平台，我们筛选了95种中草药，并鉴定出苏木查尔酮（Sap）作为一种有效的低毒性FAPα抑制剂。Sap在多种雄性小鼠肝纤维化模型中显著减轻纤维化进展并改善肝功能。机制上，Sap通过抑制FAPα-PI3K-AKT信号通路抑制肝星状细胞活化。这些发现确立了Cs-FAP作为纤维化成像和药物发现的多功能平台，并鉴定Sap为有前景的抗纤维化候选药物。
Abstract
Liver fibrosis can progress to cirrhosis and hepatocellular carcinoma, yet effective antifibrotic therapies remain limited. Fibroblast activation protein α (FAPα) is a promising biomarker and therapeutic target, but existing probes are constrained by limited tissue penetration and single-modality imaging, and effective FAPα-targeted antifibrotic agents remain lacking. Here we show that Cs-FAP, a hemicyanine-based near-infrared fluorescence/photoacoustic dual-modal probe, enables real-time and noninvasive visualization of FAPα activity in fibrotic liver tissue. Using a Cs-FAP-guided screening platform integrating high-content imaging and chromatographic purification, we screened 95 medicinal herbs and identified sappanchalcone (Sap) as a potent low-toxicity FAPα inhibitor. Sap markedly attenuated fibrosis progression and improved liver function in multiple liver fibrosis models using male mice. Mechanistically, Sap suppressed hepatic stellate cell activation through inhibition of the FAPα-PI3K-AKT signaling pathway. These findings establish Cs-FAP as a versatile platform for fibrosis imaging and drug discovery and identify Sap as a promising antifibrotic candidate.
如何引用
AMA
Wenze Zhang, Jiwei Li, Lei Sun, Chaoran Li, Kaiyu Zhang, Zhiying He, et al. Molecular imaging-guided discovery of a potent natural FAPα inhibitor for liver fibrosis therapy.. Nature communications. 2026; doi:10.1038/s41467-026-75493-9.
APA
Wenze Zhang, Jiwei Li, Lei Sun, Chaoran Li, Kaiyu Zhang, Zhiying He, et al (2026). Molecular imaging-guided discovery of a potent natural FAPα inhibitor for liver fibrosis therapy.. Nature communications. https://doi.org/10.1038/s41467-026-75493-9
GB/T 7714
Wenze Zhang, Jiwei Li, Lei Sun, Chaoran Li, Kaiyu Zhang, Zhiying He, et al. Molecular imaging-guided discovery of a potent natural FAPα inhibitor for liver fibrosis therapy.[J]. Nature communications, 2026 doi:10.1038/s41467-026-75493-9.
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