IDENTIFICATION AND CHARACTERIZATION OF INHIBITORS OF PEPTIDE-LEUKOTRIENE-SYNTHESIS FROM PETASITES HYBRIDUS

Extracts from Petasites hybridus were found to inhibit peptido-leukotr iene biosynthesis in isolated peritoneal macrophages. Chemical analysi s by gas chromatography coupled with mass and infrared spectroscopy fa cilitated the identification of three isomeric oxopetasan esters, peta sin, and isopetasin as the main compounds of these extracts. Fractiona tions obtained by column chromatography of the most effective extract indicated a correlation between peptido-leukotriene biosynthesis inhib ition and the content of isopetasin, a sesquiterpene ester of isopetas ol and angelic acid, as well as the isomeric oxopetasan esters. Petasi n, a structural isomer of isopetasin, however, was found to be inactiv e. It may even reduce the peptido-leukotrine inhibitory effect of isop etasin. It is concluded that isopetasin and the oxopetasan esters in P etasites hybridus inhibit the biosynthesis of the vasoconstrictive pep tido-leukotrienes. This effect may contribute to some of the medicinal properties of Petasites hybridus extracts such as, e.g., gastroprotec tion and spasmolytic activity.