时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
To determine whether flupirtine inhibited fibrogenesis was associated with increased l-asp and ASNS inhibition, we treated the acHSC with l-asp and found that l-asp treatment decreased calcium levels in cells and isolated mitochondria in a dose-dependent manner (Supporting Information Fig.
方法
Using a drug repositioning or drug rescue (DDDR) strategy, we identified the anti-analgesic agent flupirtine as a potential anti-liver fibrosis candidate through cell-based high-throughput screening of the FDA-approved drug library.；Treatment with flupirtine reversed TGF-β1-induced fibrogenesis and ameliorated liver fibrosis in CCl4 or DDC diet-treated fibrotic mice.；Importantly, ASNS levels were increased in activated hepatic stellate cells (acHSCs) and in the livers of fibrotic mice and humans, and are positively correlated with the severity of liver fibrosis.
核心结论
These findings have advanced anti-fibrosis research and provided a solid foundation for the development of new anti-fibrosis agents.Drug repurposing14,15, also referred to as drug repositioning or drug rescue (DDDR), emerged in the early 1990s as a viable alternative to conventional de novo drug discovery and development (DDD) methods.；Examination of caspase 3 activity in the liver demonstrated that flupirtine treatment ameliorated CCl4-induced liver injury (Fig. 2E).；Gene set enrichment analysis (GSEA) also demonstrated that the degradation of extracellular matrix and collagen degradation were highly annotated upon flupirtine treatment (Fig. 3C).
局限
However, there is no approved therapeutic medication to treat this devastating disease.；However, in response to liver injury, HSCs are activated and transform into proliferative and contractile myofibroblast-like cells.；However, the role of calpain 1 to fibrotic liver disease and relevant pathological mechanisms are less reported.
对本项目的价值
中高价值：属「线粒体质量控制与氧化应激」方向；线粒体功能与氧化应激栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
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原文题录
- 中文题名：氟吡汀经靶向天冬酰胺合成酶抑制 calpain 1/复合物 I/mtROS 轴保全线粒体质量，成为小鼠肝纤维化候选药物
- 英文标题：Identification of flupirtine as a candidate against liver fibrosis in mice: Preserving mitochondria quality by suppressing calpain 1/complex I/mtROS axis via targeting asparagine synthase.
- 期刊与标识：Acta pharmaceutica Sinica. B · PMID 42979452 · DOI 10.1016/j.apsb.2026.08.017 · PMC PMC13729717