Anti-inflammatory properties of deacilcinaropicrin from Cyclolepis genistoides

Abstract

Chronic inflammation is considered a common pathological mech- anism in many diseases including cancer, heart disease, diabetes, arthritis, and neurodegenerative disorders. Combating inflammation with plants and natural compounds is thought to be a strategy for replacing current therapy that causes severe side effects. The aim of our work was to study the anti- inflammatory properties of bioac- tive constituents from the aqueous extract of Cyclolepis genistoides D. Don (Asteraceae). This plant has been used in folk medicine in northern and central Argentina for bone pain (analgesic properties) and as a diuretic in kidney diseases. The metabolite analysis of the aqueous extract by LC-HRMS revealed the presence of coumarins (isofraxidin, fraxetin), phenolic compounds (caffeoylquinic acids and their sulfate derivatives, luteolin and its glucuronide, luteolin-7-sul- fate) and two sesquiterpene lactones, deacylcynaropicrin (DACP) and its 11,13-dihydro derivative (DH-DACP). In our lab, we previous- ly demonstrated the ability of C. genistoides and DACP to modulate the transcription factor NFμB by blocking its nuclear translocation. To gain more insight in the anti-inflammatory potential, the pharma- cological activity was also evaluated in other inflammation-related cellular in vitro models. We found that DACP (20 μM) inhibited not only NFμB1 but also COX-2 gene expression in PMA-differentiated and LPS-stimulated THP-1 cells. In addition, nitric oxide production was inhibited by DACP in microglial BV-2 cells exposed to LPS and IFN-γ (IC50 = 10.4 +/- 0.7 μM). However, DH-DACP (20 μM) had no effect on the studied pro-inflammatory pathways. The difference in pharmacological properties of both sesquiterpene lactones could be explained by the Michael acceptor moiety present in the DACP structure. Taken together, we hypothesize that DACP could be a lead compound for the development of anti-inflammatory agents due to its ability to inhibit NFκB pathway.