Inhibitory effects of hexahydro-β-acids in LPS-stimulated murine macrophage

Hexahydro-β-acids (HBA), reduced derivatives of β-acids (BA) from hop plant Humulus lupulus, are shown to be more stable than BA with stronger activities. Here, we investigated the inhibitory effects of HBA on the induction of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses demonstrated that HBA significantly blocked protein and mRNA expression of iNOS and COX-2 in LPS-induced macrophages. Treatment with HBA resulted in the reduction of LPS-induced nuclear translocation of nuclear factor-κB (NFκB) subunit and the dependent transcriptional activity of NFκB by blocking phosphorylation of inhibitor κB (IκB) α and p65 and subsequent degradation of IκBα. Transient transfection experiments using NFκB reporter constructs indicated that HBA inhibits the transcriptional activity of NFκB in LPS-stimulated murine macrophages. HBA also inhibited LPS induced activation of PI3K/Akt, extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK. Taken together, these results show that HBA down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFκB through interfering with the activation PI3K/Akt/IKK and MAPK.

► Hexahydro-β-acids (HBA) exhibited higher anti-inflammatory activity than β-acids (BA).
► HBA markedly inhibited iNOS and COX-2 gene expression by inhibiting the activation of NFκB.
► HBA inhibiting the activation of NFκB through interfering with the activation PI3K/Akt/IKK and MAPK.