Inhibiting HSCs Activation and Ameliorating Alcoholic Liver Fibrosis by Fucoidan Targeting the TLR4/NF‐κB Pathway

ABSTRACT Alcoholic liver fibrosis (ALF) is a disease characterized by excessive deposition of liver fibrous tissue due to long‐term heavy alcohol consumption. Fucoidan is a naturally occurring sulfated polysaccharide extracted from brown algae. In terms of liver protection, fucoidan has shown an important role in the treatment of alcoholic liver injury. However, its therapeutic effects on ALF and the underlying mechanisms have not been fully elucidated. The objective of this study is to investigate the mechanism of fucoidan in ALF through network pharmacology, and to validate these findings using molecular docking technology and in vivo experiments. Molecular docking results showed that fucoidan had a strong binding affinity with toll‐like receptor 4 (TLR4), nuclear factor‐κB (NF‐κB), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6), suggesting its potential to modulate the TLR4/NF‐κB pathway. In animal studies, the expression levels of proteins involved in the TLR4/NF‐κB signaling pathway were significantly decreased in mice treated with fucoidan. Fucoidan also inhibited the production of TNF‐α, IL‐1β, and IL‐6, while reducing the expression of α‐SMA, Collagen‐I, and Collagen‐III. These findings indicate that fucoidan could significantly alleviate alcohol + CCl 4 ‐induced ALF in mice by inhibiting the activation of hepatic stellate cells (HSCs).