Chimie médicale

Anti-inflammatory Properties of an Active Sesquiterpene Lactone and its Structure-Activity Relationship

Abstract

Yang Hu, Fei Zhang, Chaofeng Zhang and Mian Zhang

A sesequiterpenoid, 2α-hydroxyl-3β-angeloylcinnamolide (HAC) was isolated from the Chinese medicinal herb Polygonum jucundum Lindex. (Polygonaceae) with anti-inflammatory activities in vivo. In the present study, we investigated the anti-inflammation effects of HAC on lipopolysaacharide (LPS)-induced murine RAW264.7 cells. As the results, we found that HAC dose-dependently decreased NO over-production with IC50 value of 17.68 μM but showed very weak inhibition on TNF-α release with IC50 value of 98.66 μM. Meanwhile, eight novel derivatives modified at C-2 position of HAC were synthesized to further explore the structure-activity relationships (SARs) of HAC on antiinflammation effects. Compound PJH-1, an acetyl easer of HAC, showed better inhibition on over-production of NO and TNF-α (IC50, 7.31 and 3.38 μM, respectively). Furthermore, we demonstrated that HAC and PJH-1 attenuates the mitogen-activated protein kinases (MAPK) signaling pathways through blocking the phosphorylation of ERK, p38, JNK/MAPK. We also found that the structure of PJH-1 are more stable than that of HAC in cell medium, these finding are useful to develop in vitro molecular mechanism research of HAC. In a conclusion, our studies enhance the understanding of anti-inflammation activities of HAC and lead to the discovery of novel derivatives as potential antiinflammation agents.