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Molecules. 2018 Feb 24;23(2). pii: E506. doi: 10.3390/molecules23020506.

Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G.

Author information

1
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University, Philosophenweg 14, D-07743 Jena, Germany. andreas.koeberle@uni-jena.de.
2
Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University, Auf der Morgenstelle 8, D-72076 Tuebingen, Germany. arne.henkel@gmail.com.
3
Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University, Auf der Morgenstelle 8, D-72076 Tuebingen, Germany. mzverhoff@googlemail.com.
4
Institute of Pharmaceutical Chemistry, University of Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany. l.tausch@yahoo.de.
5
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University, Philosophenweg 14, D-07743 Jena, Germany. stefanie.koenig@uni-jena.de.
6
Department of Pharmaceutical Technology, Institute of Pharmacy, Friedrich-Schiller-University, Otto-Schott-Strasse 41, D-07745 Jena, Germany. dagmar.fischer@uni-jena.de.
7
Organic Chemistry II, Saarland University, Campus C4.2, D-66123 Saarbruecken, Germany. dr.nicole.kolz@t-online.de.
8
Organic Chemistry II, Saarland University, Campus C4.2, D-66123 Saarbruecken, Germany. seitz.stefanie@gmx.net.
9
Organic Chemistry II, Saarland University, Campus C4.2, D-66123 Saarbruecken, Germany. m.paulpaul@web.de.
10
Organic Chemistry II, Saarland University, Campus C4.2, D-66123 Saarbruecken, Germany. j.jauch@mx.uni-saarland.de.
11
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University, Philosophenweg 14, D-07743 Jena, Germany. oliver.werz@uni-jena.de.

Abstract

Age-related diseases, such as osteoarthritis, Alzheimer's disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging.

KEYWORDS:

5-lipoxygenase; boswellic acid; cathepsin; frankincense; microsomal prostaglandin E2 synthase; triterpene acid

PMID:
29495286
PMCID:
PMC6017322
DOI:
10.3390/molecules23020506
[Indexed for MEDLINE]
Free PMC Article

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