Triterpene acids from frankincense and semi-synthetic derivatives that inhibit 5-Lipoxygenase and Cathepsin G

  • 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.

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Author:Andreas KoeberleORCiD, Arne Henkel, Moritz VerhoffGND, Lars Tausch, Stefanie König, Dagmar Fischer, Nicole Kather, Stefanie Seitz, Michael Paul, Johann Jauch, Oliver WerzORCiD
URN:urn:nbn:de:hebis:30:3-478554
DOI:https://doi.org/10.3390/molecules23020506
ISSN:1420-3049
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29495286
Parent Title (English):Molecules
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/02/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/11/20
Tag:5-lipoxygenase; boswellic acid; cathepsin; frankincense; microsomal prostaglandin E2 synthase; triterpene acid
Volume:23
Issue:2, Art. 506
Page Number:14
First Page:1
Last Page:14
Note:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
HeBIS-PPN:440678390
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0