Anti-inflammatory effects of taurocholic acid and tauroursodeoxycholic acid from rainbow trout spleen extract via NF-κB suppression

Inflammation is an essential innate immune response, yet excessive or persistent inflammation contributes to chronic inflammatory diseases. Our previous studies demonstrated that rainbow trout spleen extracts possess potent anti-inflammatory activity, primarily concentrated in the butanol fraction (OSB), through suppression of NF-κB signaling and macrophage M1 polarization. However, the complex composition of OSB and the requirement for high effective concentrations limited its translational potential. In this study, we try to identify the key bioactive components responsible for OSB’s anti-inflammatory effects. The five major constituents enriched in OSB were further fractionated into two subfractions, among which B-TT, containing taurocholic acid (TCA) and tauroursodeoxycholic acid (TUDCA), exhibited the most pronounced anti-inflammatory activity. Mechanistically, B-TT significantly inhibited lipopolysaccharide (LPS) induced NF-κB activation in RAW264.7 macrophages by suppressing phosphorylation dependent IκBα degradation, thereby blocking nuclear translocation of the p65 subunit. This inhibition led to reduced iNOS expression, decreased pro-inflammatory cytokine transcription, suppression of M1 macrophage surface markers, and attenuation of intracellular reactive oxygen species (ROS) generation. Collectively, these findings demonstrate that B-TT effectively suppresses LPS-induced macrophage M1 polarization via inhibition of NF-κB signaling and indicate that TCA and TUDCA are major anti-inflammatory constituents present in rainbow trout spleen extracts, highlighting fish-derived visceral byproducts as sustainable bioresources for anti-inflammatory applications.