We investigated the effect of
ferulic acid (FA) and
isoferulic acid (IFA), which are active components of the rhizoma of Cimicifuga species used frequently as anti-inflammatory drugs in Japanese Oriental medicines, on murine
interleukin-8 (IL-8) production in response to influenza virus
infections in vitro and in vivo by antibody-sandwich
enzyme-linked
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 absence of drugs. Both FA and IFA reduced the
IL-8 levels in the 20-h
conditioned medium in comparison with control in a dose-dependent manner. The 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 micrograms/ml of IFA and FA, respectively. In the in vivo study, mice were infected with 1,000 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 showed a tendency to reduce
IL-8 levels in bronchoalveolar lavage (BAL) obtained 2 days after
infection. Moreover, both FA and IFA also significantly reduced the number of exuded neutrophils into BAL. However, the
drug 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-inflammatory rhizoma of Cimicifuga species.