Resolvin D1 alleviates liver inflammation and fibrosis through SIRT1-mediated NF-κB and TGF-β1/Smads pathways.

OBJECTIVE: Resolvin D1 (RvD1) is lipid mediator converted from docosahexaenoic acid (DHA) and has multiple pharmacological properties. Recently, it has been reported that RvD1 alleviates tissue fibrosis, including renal and pulmonary fibrosis in animal models. Here, we investigate the effects of RvD1 on liver fibrosis models in vitro and in vivo and the underlying mechanism. METHODS: Male C57BL/6 mice treated with carbon tetrachloride (CCl4) and lipopolysaccharide (LPS)-activated LX-2 cells were used in the study. The serum levels of ALT and AST were analyzed to evaluate liver function. H&E and Sirius red staining were used to assess liver morphology and the degree of liver fibrosis. Quantitative RT-PCR and western blot were used to assay the gene expression and protein levels. RESULTS: In vivo, the results showed that RvD1 significantly attenuated increased AST and ALT serum levels in CCl4-treated mice. Histological examination revealed that RvD1 ameliorated CCl4-induced fibrous proliferation and macrophage infiltration. Besides, RvD1 depressed the expressions of pro-fibrotic factors (α-SMA, Collagen I and TIMP-1) and pro-inflammatory factors (IL-6, IL-1β, TNF-α and MCP-1) in the liver tissues of model mice. In vitro, RvD1 also relieved LPS-induced inflammation and hepatic stellate cell (HSC) activation in LX-2 cells. Furthermore, RvD1 was demonstrated to upregulate the expression of SIRT1, while inhibited the p-IκBα, p-NF-κB, TGF-β1, p-Smad2 and p-Smad3 protein levels in these models. CONCLUSIONS: Our results suggest that RvD1 alleviates liver inflammation and fibrosis through SIRT1-mediated NF-κB and TGF-β1/Smads pathways and may be used as a novel therapeutic intervention for liver fibrosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12950-026-00492-y.