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

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.

Keywords

• Eriodictyol
• Non-alcoholic fatty liver disease
• UBA52
• Nrf2
• Autophagy
• Oxidative stress