Unknown

Dataset Information

0

Tetra- and pentacyclic triterpene acids from the ancient anti-inflammatory remedy frankincense as inhibitors of microsomal prostaglandin E(2) synthase-1.


ABSTRACT: The microsomal prostaglandin E2 synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E2 from cyclooxygenase (COX)-derived PGH2. We previously found that mPGES-1 is inhibited by boswellic acids (IC50 = 3-30 ?M), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1 with increased potencies. In particular, 3?-acetoxy-8,24-dienetirucallic acid (6) and 3?-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC50 = 0.4 ?M, each. Structure-activity relationship studies and docking simulations revealed concrete structure-related interactions with mPGES-1 and its cosubstrate glutathione. COX-1 and -2 were hardly affected by the triterpene acids (IC50 > 10 ?M). Given the crucial role of mPGES-1 in inflammation and the abundance of highly active triterpene acids in frankincence extracts, our findings provide further evidence of the anti-inflammatory potential of frankincense preparations and reveal novel, potent bioactivities of tirucallic acids, roburic acids, and lupeolic acids.

SUBMITTER: Verhoff M 

PROVIDER: S-EPMC4074212 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Tetra- and pentacyclic triterpene acids from the ancient anti-inflammatory remedy frankincense as inhibitors of microsomal prostaglandin E(2) synthase-1.

Verhoff Moritz M   Seitz Stefanie S   Paul Michael M   Noha Stefan M SM   Jauch Johann J   Schuster Daniela D   Werz Oliver O  

Journal of natural products 20140520 6


The microsomal prostaglandin E2 synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E2 from cyclooxygenase (COX)-derived PGH2. We previously found that mPGES-1 is inhibited by boswellic acids (IC50 = 3-30 μM), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1  ...[more]

Similar Datasets

| S-EPMC1435722 | biostudies-literature
| S-EPMC6017322 | biostudies-literature
| S-EPMC3546279 | biostudies-literature
| S-EPMC3182462 | biostudies-literature
| S-EPMC4020105 | biostudies-literature
| S-EPMC1566188 | biostudies-literature
| S-EPMC1518807 | biostudies-literature
| S-EPMC8351447 | biostudies-literature
| S-EPMC10411941 | biostudies-literature
| S-EPMC4743789 | biostudies-literature