Pseudonatural Flavonols as Novel Copper Ionophores for NAFLD Intervention via Synergistic Copper Delivery and Flavonoid Activity
文献类型： 外文期刊
作者： Jiang, Jun 1 ; Chen, Gang 1 ; Zhang, Weiqin 3 ; Qin, Si 4 ; Li, Man 5 ; Zhong, Shiyi 1 ; Yang, Ying 1 ; Yang, Liuxin 1 ; Shao, Muqing 4 ; Wang, Kai 1 ; Li, Qin 4 ; Jiang, Chen 1 ; Yang, Jingfang 6 ; Wang, Fang 3 ; Qiu, Shuang 2 ; Li, Xiang 1 ;
作者机构： 1.Hubei Univ, Sch Hlth Sci & Engn, Wuhan 430062, Hubei, Peoples R China
2.Northeast Forestry Univ, Coll Chem, Chem Engn & Resource Utilizat, Harbin 150040, Heilongjiang, Peoples R China
3.MetWare Biotechnol Co Ltd, Wuhan 430075, Hubei, Peoples R China
4.Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 3, Chongqing 401120, Peoples R China
5.Hubei Univ Sci & Technol, Hubei Engn Res Ctr Tradit Chinese Med South Hubei, Sch Pharm, Xianning 437100, Hubei, Peoples R China
6.Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing 100193, Peoples R China
7.Wuhan Text Univ, Natl Local Joint Engn Lab Adv Text Proc & Clean Pr, Wuhan 430073, Hubei, Peoples R China
期刊名称：JOURNAL OF MEDICINAL CHEMISTRY （ 影响因子：6.8； 五年影响因子：7.2 ）
ISSN： 0022-2623
年卷期： 2025 年 68 卷 6 期
页码：
收录情况： SCI
摘要： Copper plays crucial roles in fundamental life processes, including proliferation, metabolism, and survival. Copper deficiency is associated with multiple diseases, such as nonalcoholic fatty liver disease (NAFLD) and Wilson's disease. Therapeutic programs targeting copper supply are prospectively employed for disease intervention. Herein, we developed biofriendly copper ionophores (HQFs) by constructing pseudonatural flavonols, which possess flavonoid bioactivity and enhanced copper transport properties. In cell models and mice, we found that HQF-mediated copper delivery synergistically, safely, and efficiently intervened in the development of fatty liver. Mechanistically, NAFLD remission involves fatty acid metabolism, anti-inflammatory processes, and pentose phosphate pathway (PPP) enhancement. Our work is the first to propose the utilization of synergistic copper loading and flavonoid activity for NAFLD intervention, which may inform the clinical management of liver disease.
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