Eriodictyol downregulates UBA52 to promote autophagy and upregulates Nrf2/HO-1 to inhibit oxidative stress to ameliorate non-alcoholic fatty liver disease

作者全名："Cai, Yongqing; Yuan, Lie; Wang, Kaiyang; Liu, Qinglong; Xing, Haiyan; Zhong, Peiling; Lin, Jinjian; Liang, Yuan; Chen, Gefei; Li, Wenjun; Chen, Jianhong; Li, Xiaoli"

作者地址："[Cai, Yongqing; Wang, Kaiyang; Xing, Haiyan; Chen, Jianhong] Army Med Univ, Daping Hosp, Dept Pharm, Chongqing, Peoples R China; [Yuan, Lie; Zhong, Peiling; Li, Xiaoli] Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing, Peoples R China; [Yuan, Lie; Lin, Jinjian; Li, Xiaoli] Key Lab Biochem & Mol Pharmacol, Chongqing, Peoples R China; [Liu, Qinglong; Li, Wenjun] Chongqing Med Univ, Affiliated Hosp 3, Dept Pharm, Chongqing, Peoples R China; [Chen, Gefei] Karolinska Inst, Dept Biosci & Nutr, Huddinge 14157, Sweden"

通信作者："Chen, JH (通讯作者)，Army Med Univ, Daping Hosp, Dept Pharm, Chongqing, Peoples R China.; Li, XL (通讯作者)，Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing, Peoples R China.; Li, WJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Pharm, Chongqing, Peoples R China."

来源：JOURNAL OF FUNCTIONAL FOODS

ESI学科分类：AGRICULTURAL SCIENCES

WOS号：WOS:001178488900001

JCR分区：Q1

影响因子：5.6

年份：2024

卷号：113

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Eriodictyol; Non-alcoholic fatty liver disease; UBA52; Nrf2; Autophagy; Oxidative stress

摘要："Eriodictyol (Eri) is a widely distributed flavonoid compound. We explored the effect of Eri on non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism. Eri reduced hepatic lipid accumulation and alanine aminotransferase, aspartate aminotransferase, cholesterol, and triglyceride levels in high-fat diet-induced NAFLD mice. Proteomics analysis showed that Eri regulated oxidative stress- and autophagy-related signaling pathways. Eri treatment upregulated MAP1LC3 (LC3)II/I, nuclear factor E2-related factor (Nrf2), and heme oxygenase 1 (HO-1), downregulated Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) and SQSTM1 (p62), inhibited p-nuclear factor-kappa B (p-NF-kappa B), and reduced tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) release. UBA52 knockdown or Eri treatment promoted autophagy in oil acid-induced HepG2 cells. UBA52 knockdown combined with Eri treatment produced a more prominent effect than either of the treatments alone. Eri also significantly ameliorated hepatic lipid accumulation in db/db mice. Thus, Eri ameliorated NAFLD by downregulating UBA52 to promote autophagy and activated Nrf2/HO-1 to inhibit oxidative stress. Eri might be a potential compound for treating NAFLD."

基金机构：Chongqing Clinical Pharmacy Key Specialties Construction Project; Central Guidance for Local Scientific and Technological Development Special Project of Sichuan Province [2023ZYD0283]; Chongqing Health and Family Planning Commission [2019MSXM010]

基金资助正文："This research was funded by the Chongqing Clinical Pharmacy Key Specialties Construction Project, Central Guidance for Local Scientific and Technological Development Special Project of Sichuan Province (2023ZYD0283) and Chongqing Health and Family Planning Commission (2019MSXM010) ."