Curcumin Attenuates Liver Fibrosis and Inflammation by Modulating Slamf8-Mediated TNF/NF-κB Signaling

Liver fibrosis (LF) is characterized by inflammation and fibrosis following liver injury. Curcumin has anti-inflammatory, antioxidant, and cytoprotective properties, with benefits in managing liver diseases. However, the specific mechanisms underlying these effects remain obscure. This work aims to probe into the potential mechanism of curcumin treating LF.We used CCL4 to construct a liver fibrosis model and treated with low, medium, and high concentrations of curcumin. Subsequently, we collected liver tissues and performed RNA sequencing to identify potential targets and associated signaling pathways affected by curcumin treatment. The results showed that curcumin significantly reduced liver damage in mice induced with carbon tetrachloride. RNA sequencing results indicated that Slamf8 was a likely target and the Slamf8 expression was notably decreased in the curcumin group. According to in vivo and vitro results, curcumin inhibited the TNF/NF-κB pathway via Slamf8 modulation, reducing release of pro-inflammatory cytokines (IL-6, IL-17A, MCP-1). Curcumin also suppressed the expression of LF-associated proteins, including α-SMA, COL1A1 and FN. In summary, curcumin exerts potent anti-fibrotic and anti-inflammatory effects by modulating Slamf8 to influence the TNF/NF-κB pathway, thus protecting the liver.