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Article Publish Status: FREE
Abstract Title:

Identification of human cathepsin G as a functional target of boswellic acids from the anti-inflammatory remedy frankincense.

Abstract Source:

J Immunol. 2009 Sep 1 ;183(5):3433-42. Epub 2009 Jul 31. PMID: 19648270

Abstract Author(s):

Lars Tausch, Arne Henkel, Ulf Siemoneit, Daniel Poeckel, Nicole Kather, Lutz Franke, Bettina Hofmann, Gisbert Schneider, Carlo Angioni, Gerd Geisslinger, Carsten Skarke, Wolfgang Holtmeier, Tobias Beckhaus, Michael Karas, Johann Jauch, Oliver Werz

Article Affiliation:

Lars Tausch

Abstract:

Frankincense preparations, used in folk medicine to cure inflammatory diseases, showed anti-inflammatory effectiveness in animal models and clinical trials. Boswellic acids (BAs) constitute major pharmacological principles of frankincense, but their targets and the underlying molecular modes of action are still unclear. Using a BA-affinity Sepharose matrix, a 26-kDa protein was selectively precipitated from human neutrophils and identified as the lysosomal protease cathepsin G (catG) by mass spectrometry (MALDI-TOF) and by immunological analysis. In rigid automated molecular docking experiments BAs tightly bound to the active center of catG, occupying the same part of the binding site as the synthetic catG inhibitor JNJ-10311795 (2-[3-[methyl[1-(2-naphthoyl)piperidin-4-yl]amino]carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid). BAs potently suppressed the proteolytic activity of catG (IC(50) of approximately 600 nM) in a competitive and reversible manner. Related serine proteases were significantly less sensitive against BAs (leukocyte elastase, chymotrypsin, proteinase-3) or not affected (tryptase, chymase). BAs inhibited chemoinvasion but not chemotaxis of challenged neutrophils, and they suppressed Ca(2+) mobilization in human platelets induced by isolated catG or by catG released from activated neutrophils. Finally, oral administration of defined frankincense extracts significantly reduced catG activities in human blood ex vivo vs placebo. In conclusion, we show that catG is a functional and pharmacologically relevant target of BAs, and interference with catG could explain some of the anti-inflammatory properties of frankincense.

Study Type : Human Study

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Sayer Ji
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