Chalcones from Angelica keiskei Attenuate the Inflammatory Responses by Suppressing Nuclear Translocation of NF- κB.

The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones ( 1- 7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine ( 1), xanthoangelol E ( 2), xanthokeismin A ( 4), and xanthoangelol B ( 5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory- κB α (I- κB α) and the translocation of nuclear factor κB (NF- κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones ( 1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I- κB α and nuclear translocation of NF- κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]