isoferulic-acid and Orthomyxoviridae-Infections

Isoferulic acid (IFA) is a main active ingredient of the rhizoma of Cimicifuga beracleifolia, which is used frequently in Japanese traditional medicine as an anti-inflammatory drug. It has been revealed that IFA inhibits the production of macrophage inflammatory protein-2 (MIP-2), which is a murine counterpart of the chemokine family that may contribute to the pathogenesis of inflammatory diseases through the chemotactic activity for inflammatory and immune effector cells.. In this study, we investigated the therapeutic effect of IFA on the progression of lethal influenza virus pneumonia in mice by comparison with that of dexamethasone (DX), a potent inhibitor for various inflammatory cytokines including MIP-2.. Mice were infected by intranasal inoculation of influenza virus under ether anesthesia. The IFA or DX was given by oral administration once daily for 4 days after infection. After infection, the survival rate and the change in body weight were daily monitored.. IFA administration markedly improved the survival rate and body weight loss of influenza virus-infected mice in a suitable dose range (0.5 mg/day). However, DX administration did not show a beneficial effect at any dose.. These data suggested that IFA is a novel tool not only for the intervention therapy, but also for the studies on the pathogenesis of influenza virus-induced pneumonia.

Topics: Animals; Anti-Inflammatory Agents; Cinnamates; Dexamethasone; Influenza A virus; Japan; Medicine, East Asian Traditional; Mice; Orthomyxoviridae Infections; Pneumonia, Viral

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.

Topics: Animals; Antihypertensive Agents; Cell Line; Chick Embryo; Cinnamates; Coumaric Acids; Female; Influenza A virus; Interleukin-8; Lipopolysaccharides; Lung; Macrophages; Mice; Mice, Inbred ICR; Neutrophils; Orthomyxoviridae Infections; Plants, Medicinal