Antipyretic activity of cinnamyl derivatives and related compounds in influenza virus-infected mice.

Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic activity by suppressing interleukin-1alpha production responsive to interferon in a murine intranasal influenza virus infection model. Using this model, antipyretic compounds with such novel biological activities were characterized from the herbs. The organic solvent-extractable fractions of Cinnamomum cassia among the herbs showed antipyretic activity. We selected six antipyretic compounds from 48 cinnamyl derivatives and related compounds that may be mainly involved in the fractions. Their antipyretic activity was significantly correlated with interleukin-1alpha regulatory activity. Four of them suppressed interleukin-1alpha production to a basal level and showed different mode of antipyretic action from that of aspirin in interleukin-1alpha-injected mice. Structure-bioactivity relationship of the four suggested that an ester bond played an important role for both antipyretic and interleukin-1alpha regulatory activities. These compounds may be useful in analyzing interleukin-1alpha-producing cells in fever production and the mechanism of defervescence by suppressing interferon-induced interleukin-1alpha production.