Abstract
Frankincense extracts and boswellic acids, biologically active pentacyclic triterpenes of frankincense, block leukotriene biosynthesis and exert potent anti-inflammatory effects. Screening for additional effects of boswellic acids on further proinflammatory pathways, we observed that acetyl-11-keto-β-boswellic acid, an established direct, nonredox and noncompetitive 5-lipoxygenase inhibitor, decreased the activity of human leukocyte elastase (HLE) in vitro with an IC50 value of about 15 μM. Among the pentacyclic triterpenes tested in concentrations up to 20 μM, we also observed substantial inhibition by β-boswellic acid, amyrin and ursolic acid, but not by 18β-glycyrrhetinic acid. The data show that the dual inhibition of 5-lipoxygenase and HLE is unique to boswellic acids: other pentacyclic triterpenes with HLE inhibitory activities (e.g., ursolic acid and amyrin) do not inhibit 5-lipoxygenase, and leukotriene biosynthesis inhibitors from different chemical 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 two proinflammatory enzymes by boswellic acids might be the rationale for the putative antiphlogistic activity of acetyl-11-keto-β-boswellic acid and derivatives.
Footnotes
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Send reprint requests to: Privat-Dozent Dr. H. Safayhi, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, D-72076 Tuebingen, Germany.
- Abbreviations:
- AKBA
- acetyl-11-keto-β-boswellic acid
- DMSO
- dimethylsulfoxide
- HLE
- human leukocyte elastase
- 5-LO
- 5-lipoxygenase
- LTB4
- leukotriene B4
- MK-886 (formerly designated L-663
- 536), 3-[1-(4-chlorobenzyl)-3-tert-butyl-thio-5-isopropylindol-2-yl-]-2,2-dimethylpropanoic acid
- NDGA
- nordihydroguaiaretic acid
- PBS
- Dulbecco’s phosphate-buffered saline
- PMNL
- polymorphonuclear leukocytes
- ZM-230
- 487 (formerly designated ICI-230,487: the N-ethyl-analog of ICI-D2138), 6-[[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy]methyl]-1-ethylquinol-2-one
- Received June 18, 1996.
- Accepted December 24, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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