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Anti‐inflammatory mechanism of rho‐iso‐alpha acids from hop extract
Author(s) -
Konda Veera Reddy,
Hall Amy,
Desai Anuradha,
Carroll Brian,
Darland Gary,
Bland Jeffrey S.,
Tripp Matthew
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1145-a
Subject(s) - humulus lupulus , biology , microbiology and biotechnology , nf κb , signal transduction , p38 mitogen activated protein kinases , mapk/erk pathway , chemistry , pepper , horticulture
Prostaglandin E 2 (PGE 2 ) 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 PGE 2 production in lipopolysaccharide (LPS) activated murine macrophage cell line RAW 264.7. Analysis of the mechanism shows that RIAA inhibits PGE 2 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.)