INHIBITORY EFFECT OF FERULIC ACID AND ISOFERULIC ACID ON MURINE INTERLEUKIN-8 PRODUCTION IN RESPONSE TO INFLUENZA-VIRUS INFECTIONS IN-VITROAND IN-VIVO

We investigated the effect of ferulic acid (FA) and isoferulic acid (I FA), which are active components of the rhizoma of Cimicifuga species used frequently as anti-inflammatory drugs in Japanese Oriental medici nes, on murine interleukin-8 (IL-8) production in response to influenz a virus infections in vitro and in vivo by antibody-sandwich enzyme-li nked immunosorbent assay. In the in vitro study, the murine macrophage cell Line RAW 264.7 was infected with influenza virus at a dose of 10 plaque forming units (PFU)/cell and cultured in the presence or absen ce of drugs. Both FA and IFA reduced the IL-8 levels in the 20-h condi tioned medium in comparison with control in a dose-dependent manner. T he effect of IFA was greater than that of FA: IL-8 levels were reduced to 43% and 56% of the control in the presence of 100 mu g/ml of IFA a nd FA, respectively. In the in vivo study, mice were infected with 1,0 00 PFU of virus and received daily oral administrations of Cimicifuga heracleifolia extract (5 mg/mouse/day), FA (0.5 mg/mouse/day), IFA (0. 125 mg/mouse/day), or phosphate buffered saline. The three drugs showe d a tendency to reduce IL-8 levels in bronchoalveolar lavage (BAL) obt ained 2 days after infection. Moreover, both FA and IFA also significa ntly reduced the number of exuded neutrophils into BAL, However, the d rug administrations did not affect the virus yields in BAL. These data suggest that FA and IFA are novel and potent inhibitors of murine IL- 8 production and might act as one of the main components of anti-infla mmatory rhizoma of Cimicifuga species.