文献类型：期刊文献

英文题名：Drug repurposing of glucosamine to ameliorate alcoholic liver disease and delay liver aging through activation of AMPK signaling pathway

作者：Song, Yihe[1,4];Li, Wei[1];Shao, Qiqi[1];Huang, Junyang[1];Guo, Xiaobo[1];Wang, Xicheng[1];Gu, Chao[1];Ke, Jiahui[1];Zhu, Tong[1];Gao, Xiaojie[1];Liu, Wenwen[3];Wang, Manjiong[1];Li, Jian[1,2,3];Xu, Yixiang[1];Li, Xiaokang[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Pharm,State Key Bioreactor Engn,Shanghai Key L, Shanghai 200237, Peoples R China;[2]Shihezi Univ, Sch Pharm, Key Lab Xinjiang Phytomed Resource & Utilizat, Minist Educ, Shihezi 832003, Peoples R China;[3]Hainan Univ, Coll Pharm, Key Lab Trop Biol Resources, Minist Educ, Haikou 570228, Peoples R China;[4]Naval Med Univ, Mil Med Univ 2, Ctr Basic Res & Innovat Med, Sch Pharm, Shanghai 200433, Peoples R China

年份：2026

卷号：1030

外文期刊名：EUROPEAN JOURNAL OF PHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-105045114050);WOS:【SCI-EXPANDED(收录号:WOS:001828197700001)】；

基金：We gratefully appreciate the financial support from the National Key Research and Development Program of China (grant 2023YFA1802004 to X.L.) , the Natural Science Foundation of Shanghai (grant 23ZR1415700 to X.L.) , the National Natural Science Foundation of China (grant 22477025 to Y.X.) , the Innovation Program of Shanghai Municipal Education Commission (grant 202101070002E00104 to J.L.) , the Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (grant 2021 Sci & Tech 03-28 to J.L.) , the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering (2060204 to J.L.) . The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

语种：英文

外文关键词：Glucosamine; Alcoholic liver disease; Liver aging; Senescence intervention; Drug repurposing

摘要：Alcohol consumption is a major etiological factor for alcoholic liver disease (ALD) and accelerates liver aging, representing a progressive condition with limited therapeutic options. Recent evidence suggests that targeting hepatocellular senescence represents a promising therapeutic strategy, particularly through repurposing approved drugs capable of simultaneously ameliorating hepatic steatosis, inflammation, and liver aging. In this study, we screened reported anti-aging molecules and identified glucosamine (GlcN) as a candidate with the potential to mitigate both ALD and liver aging. In both acute and chronic mouse models of ALD, GlcN administration significantly reduced hepatic lipid accumulation, pro-inflammatory cytokine expression, and cellular senescence markers. Mechanistically, GlcN activated AMPK signaling, which subsequently suppressed the senescence-associated secretory phenotype (SASP) through modulation of the p38 MAPK pathway, and improved lipid metabolism by regulating the SREBP1/FAS and ACC pathways. These findings illustrate the multifaceted role of GlcN in ameliorating both cellular senescence and dysregulated lipid metabolism, thereby attenuating ALD progression. Our results support the repurposing of GlcN as a potential candidate for ALD and alcoholassociated liver aging.