Eriodictyol downregulates UBA52 to promote autophagy and upregulates Nrf2/HO-1 to inhibit oxidative stress to ameliorate non-alcoholic fatty liver disease
Yongqing Cai, Lie Yuan, Kaiyang Wang, Qinglong Liu, Haiyan Xing, Peiling Zhong, Jinjian Lin, Yuan Liang, Gefei Chen, Wenjun Li, Jianhong Chen, Xiaoli Li
Abstract
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-κB (p-NF-κB), and reduced tumor necrosis factor-α (TNF-α) 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.