Pinostrobin Inhibits Nuclear Factor-Kappa B Signaling and Production of Inflammatory Cytokines and Chemokines in Human Macrophages

Background/Objectives: Pinostrobin is a natural flavonoid compound, a specific type of monohydroxyflavanone, found in various plants like fingerroot and honey. It displays various biological activities such as antioxidant, antimicrobial, anti-adaptogenic and anti-inflammatory. However, the anti-inflammatory effect on human macrophages has not yet been investigated. Methods: In this study, we reported the effect of pinostrobin on inhibiting production of pro-inflammatory cytokines and chemokines in human THP-1 macrophages exposed to lipopolysaccharide. In addition, the responsible mechanisms of pinostrobin at the molecular level were identified. Results: Results from ELISA demonstrated that pinostrobin significantly inhibited production of pro-inflammatory cytokines and chemokines, including IL-6, TNF-α, IL-8, MCP-1/CCL2, and CXCL10/IP10. In addition, data from Western blot analysis revealed that pinostrobin suppressed LPS-induced NF-κB activation, in part through blocking IκB-α phosphorylation and degradation as well as NF-κB phosphorylation and nuclear translocation. Results from immunofluorescence study verified that pinostrobin effectively inhibited IκB-α degradation and NF-κB nuclear translocation. Additionally, pre-treatment of pinostrobin alone retained the existence of IκB-α in the cytoplasm of human macrophages, and this may contribute to the enhanced inhibitory activity of pinostrobin in suppressing NF-κB activation. Conclusions: This study provided accumulated evidence that pinostrobin exhibits anti-inflammatory activities, and these properties of pinostrobin in human macrophages stem from the inhibition of the NF-κB signal transduction pathway. Our findings suggest that pinostrobin may be useful for the development of therapeutic treatment of inflammation-related diseases or conditions in which NF-κB is overactive.