Imbricaric Acid and Perlatolic Acid: Multi-Targeting Anti-Inflammatory Depsides from Cetrelia monachorum

Abstract

In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E2 synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E2 synthase-1 (IC50 = 1.9 and 0.4 µM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC50 = 5.3 and 1.8 µM, resp.) and on purified enzyme (IC50 = 3.5 and 0.4 µM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC50 values of 2.0 and 7.0 µM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy.

Lichens as a source of chemical compounds with anti-inflammatory activity

“…In both trials of the inhibition of 5-LOX (both isolated and in the cells), obtained IC 50 values were 1.4 μg/ml and 1.3 μg/ml. In addition, the extract also reduced the transactivation activity of NF-κB (IC 50 2.6 μg/ml), indicating a potential importance of the anti-inflammatory activity of the tested extract [14].…”

“…5 µM). The authors of the study suggest that the inhibition of both enzymes (mPGES-1 and 5-LOX) provides a potentially more effective anti-inflammatory effect [14].…”

Drugs from nature targeting inflammation (DNTI): a successful Austrian interdisciplinary network project

“…showed strong inhibition of mPGES-1 ( IC 50 = 0.4 and 1.9 µM, respectively, on the purified enzyme), 5-lipoxygenase (5-LO) ( IC 50 = 1.8 and 5.3 µM, respectively, in a cell-based assay and IC 50 = 0.4 and 3.5 µM, respectively, on the purified enzyme), as well as of TNF-α-induced NF-κB activation ( IC 50 = 7.0 and 2.0 µM, respectively, in luciferase reporter cells). The anti-inflammatory effect of 9 was further confirmed in a murine in vivo model of inflammation, in which a significant reduction of thioglycollate-induced recruitment of leukocytes to the peritoneum was demonstrated [ 37 ] (Fig. 6 ).…”

Ingredients from Litsea garrettii as Potential Preventive Agents against Oxidative Insult and Inflammatory Response

“…Compared with those on ingredients 11 , 16 , and 18 , few findings on the antioxidant and anti-inflammatory effects of MPP have been published. It has been reported that MPP displayed inhibitions against 5-lipoxygenase [ 41 ], α -glucosidase [ 42 ], and Mycobacterium tuberculosis H37Rv in vitro [ 43 ].…”