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  3. Quercetin alleviates ethanol-induced hepatocyte senescence by interacting with glycinamide ribonucleotide transformylase

Quercetin alleviates ethanol-induced hepatocyte senescence by interacting with glycinamide ribonucleotide transformylase

  • Food Res Int. 2025 Dec;221(Pt 3):117392. doi: 10.1016/j.foodres.2025.117392.
Chen Huimin 1,  Peng Shufen 2,  Cui Zhaoyu 3,  Liu Jiaxin 3,  Chen Li 3,  Yin Xingzhu 3,  Wu Bangfu 3,  Zhao Ying 4,  Wang Yu 3,  Mo Li 3,  Liang Chanhua 3,  Li Dongyan 5,  Xu Bichao 6,  Li Yanyan 7,  Yao Ping 8,  Gao Chao 9,  Tang Yuhan 8
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Fruit Lake Street Community Health Service Center, Wuchang District, Wuhan 430000, China.
  • 3 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 4 School of Public Health, Kunming Medical University, Kunming 650500, China.
  • 5 Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 6 Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
  • 7 Shenzhen Center for Chronic Disease Control, Shenzhen 518020, China.
  • 8 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 9 Key Laboratory of Public Nutrition and Health, National Health Commission of the People's Republic of China; National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China. Electronic address: [email protected].
PMID: 41215006 DOI: 10.1016/j.foodres.2025.117392
Abstract

Quercetin demonstrates therapeutic potential for alcoholic liver disease. However, its precise molecular targets and mechanisms of action require further elucidation. This research aimed to systematically investigate its hepatoprotective mechanisms using transcriptomic and metabolomic analyses. Initially, mice fed a Lieber-DeCarli diet containing 5 % (v/v) ethanol and quercetin (100 mg/kg·bw) exhibited decreased triglyceride level, serum aminotransferase concentration, and hepatic lipid droplet accumulation. Additionally, integrated analysis of transcriptomic and metabolomic revealed significant enrichment in purine metabolic pathway, which supplies substrates for the S-phase of the cell cycle. Notably, the purine intermediate 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) was identified as the most prominently altered one under quercetin treatment (VIP = 4.237, P < 0.05). AICAR administration abrogated the anti-senescent effects of quercetin in hepatocytes, evidenced by increased SA-β-gal+ cells and elevated senescent marker (p53, p21, and p16) expression. Moreover, human proteome microarray screening and cellular thermal shift assays revealed that glycinamide ribonucleotide transformylase (GART), a rate-limiting enzyme in AICAR biosynthesis, has potential to bind with quercetin. The overexpression of GART completely negated quercetin's capacity to suppress hepatocyte senescence. In conclusion, quercetin alleviates ethanol-induced hepatocyte senescence by interacting with GART, thereby providing insights into its pharmacological action on alcoholic liver disease.

Keywords

Alcoholic liver disease; Hepatocyte senescence; Purine metabolism pathway; Quercetin.

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