Tetra-
and Pentacyclic Triterpene Acids from the Ancient
Anti-inflammatory Remedy Frankincense as Inhibitors of Microsomal
Prostaglandin E<sub>2</sub> Synthase‑1
- Publication date
- Publisher
Abstract
The microsomal prostaglandin E<sub>2</sub> synthase (mPGES)-1 is
the terminal enzyme in the biosynthesis of prostaglandin (PG)E<sub>2</sub> from cyclooxygenase (COX)-derived PGH<sub>2</sub>. We previously
found that mPGES-1 is inhibited by boswellic acids (IC<sub>50</sub> = 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
with increased potencies. In particular, 3α-acetoxy-8,24-dienetirucallic
acid (<b>6</b>) and 3α-acetoxy-7,24-dienetirucallic acid
(<b>10</b>) inhibited mPGES-1 activity in a cell-free assay
with IC<sub>50</sub> = 0.4 μM, 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 (IC<sub>50</sub> >
10 μM). 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