TY  - JOUR
A1  - Koeberle, Andreas
A1  - Henkel, Arne
A1  - Verhoff, Moritz
A1  - Tausch, Lars
A1  - König, Stefanie
A1  - Fischer, Dagmar
A1  - Kather, Nicole
A1  - Seitz, Stefanie
A1  - Paul, Michael
A1  - Jauch, Johann
A1  - Werz, Oliver
T1  - Triterpene acids from frankincense and semi-synthetic derivatives that inhibit 5-Lipoxygenase and Cathepsin G
T2  - Molecules
N2  - 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.
KW  - triterpene acid
KW  - 5-lipoxygenase
KW  - cathepsin
KW  - frankincense
KW  - boswellic acid
KW  - microsomal prostaglandin E2 synthase
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47855
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-478554
SN  - 1420-3049
N1  - 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).
VL  - 23
IS  - 2, Art. 506
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel
ER  -