Identification and isolation of medicarpin and a substituted benzofuran as potent leukotriene inhibitors in an anti-inflammatory Chinese herb

In a search for new inhibitors of leukotriene formation, a methylene chloride extract of the plant Dalbergia odorifera (Jiangxiang) was found to be a potent inhibitor of LTC4 formation in AB-CXBG Mct-1 mastocytoma cells. Following LH-20 and reverse phase HPLC chromatography, two compounds were isolated that had potent LTC4 inhibitory activity: medicarpin and 6-hydroxy-2-(2-hydroxy-4-methoxyphenyl) benzofuran (IV) with IC50s of 0.5 and 0.05 microM respectively. IV was shown to be a specific inhibitor of 5-lipoxygenase with an IC50 against the soluble rat enzyme of 0.08 microM, whereas it was inactive against cyclooxygenase. In neutrophils IV inhibited LTB4 production at comparable concentrations but had no effect on neutrophil degranulation or adhesion.