Anti‐inflammatory mechanism of rho‐iso‐alpha acids from hop extract

Abstract

Prostaglandin E2 (PGE2) has been implicated in many inflammatory diseases including rheumatoid arthritis, angiogenesis and cancer. Rho-iso-alpha acids (RIAA, modified hop extract from Humulus lupulus) inhibits PGE2 production in lipopolysaccharide (LPS) activated murine macrophage cell line RAW 264.7. Analysis of the mechanism shows that RIAA inhibits PGE2 by inhibiting cyclooxygenase-2 (COX-2) protein expression in RAW 264.7 cells. In vitro and cell-free enzymatic assays reveal that RIAA does not inhibit PGE2 production by inhibiting COX-2 enzymatic activity. RIAA inhibits NF-□B mediated signaling pathway, as evidenced by reductions in I□B□ degradation, NF-□B p50 nuclear translocation and binding, and NF-□B driven promoter activity. Moreover, the dose dependent inhibition of LPS activated murine COX-2 promoter activity by RIAA is attenuated by mutations at two NF-□B binding sites (−401 and −668) on the COX-2 promoter. Inducible nitric oxide synthase (iNOS), a known NF□B dependent gene, was also inhibited by RIAA. It appears that the anti-inflammatory properties of RIAA are independent of ERK-1/2, p38 and JNK signaling pathways. These results demonstrate that RIAA from hop extract inhibit inflammation through multiple mechanisms, including the NF-□B signaling pathway. (Supported by Metagenics Inc.)