INHIBITION BY BOSWELLIC ACIDS OF HUMAN-LEUKOCYTE ELASTASE

Frankincense extracts and boswellic acids, biologically active pentacy clic triterpenes of frankincense, block leukotriene biosynthesis and e xert potent anti-inflammatory effects. Screening for additional effect s of boswellic acids on further proinflammatory pathways, we observed that acetyl-11-keto-beta-boswellic acid, an established direct, nonred ox and noncompetitive 5-lipoxygenase inhibitor, decreased the activity of human leukocyte elastase (HLE) in vitro with an IC50 value of abou t 15 mu M. Among the pentacyclic triterpenes tested in concentrations up to 20 mu M, we also observed substantial inhibition by beta-boswell ic acid, amyrin and ursolic acid, but not by 18 beta-glycyrrhetinic ac id. The data show that the dual inhibition of 5-lipoxy-genase and HLE is unique to boswellic acids: other pentacyclic triterpenes with HLE i nhibitory activities (e.g., ursolic acid and amyrin) do not inhibit 5- lipoxygenase, and leukotriene biosynthesis inhibitors from different c hemical classes (e.g., NDGA, MK-886 and ZM-230,487) do not impair HLE activity. Because leukotriene formation and HLE release are increased simultaneously by neutrophil stimulation in a variety of inflammation- and hypersensitivity-based human diseases, the reported blockade of tw o proinflammatory enzymes by boswellic acids might be the rationale fo r the putative antiphlogistic activity of acetyl-11-keto-beta-boswelli c acid and derivatives.