Abstract: Objective: To investigate the protective effect and potential molecular mechanism of fucoidan on alcoholic liver injury. Methods: A mouse model of alcoholic liver disease (ALD) was established using 50% (V/V) alcohol, and then administered with 300 mg/kg mb of fucoidan. Liver histomorphological changes were compared in the control, ALD and fucoidan intervention groups, and the levels of serum aminotransferase, serum lipids, and inflammatory factors, the proportion of T helper (Th) cells including Th1, Th2 and Th17, and the expression levels of autophagy-related proteins and microtubule-associated protein 1 light chain 3 beta (LC3B) were detected to explore the mechanism by which fucoidan can improve alcoholic liver injury. Results: Fucoidan could improve the pathological changes of liver tissue, reduce the levels of serum alanine (aminotransferase (ALT) and aspartate aminotransferase (AST)) and blood lipids (triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and total bile acid (TBA)) (P < 0.05), and decrease the levels of serum inflammatory factors (TNF-α, IL-1β and IL-6) and the proportion of Th1, Th2 and Th17 (P < 0.05). Meanwhile, it could down-regulate the expression of autophagy-related protein p62, mammalian target of rapamycin complex 1 (mTORC1) and ribosomal protein 70S6 kinase (p70S6K) (P < 0.05), promote the nuclear translocation of transcription factor EB (TFEB) (P < 0.05), and up-regulate the expression of LC3B II protein and LC3B fluorescent protein (P < 0.05). Conclusion: Fucoidan can alleviate lipotoxicity and inflammatory injury in the liver of ALD mice, and its mechanism may be related to the activation of autophagy.

Key words: autophagy; ethanol-induced liver injury; fucoidan; blood lipids; inflammation