Anti-inflammatory Properties of an Active Sesquiterpene Lactone and its Structure-Activity Relationship
- *Corresponding Author:
- Chaofeng Zhang
State Key Laboratory of Natural Medicines
Research Department of Pharmacognosy
China Pharmaceutical University
Longmian Road 639, Nanjing 211198 PR China
E-mail: [email protected]
Received date: July 01, 2015; Accepted date: August 11, 2015; Published date: August 14, 2015
Citation: Hu Y, Zhang F, Zhang C, Zhang M (2015) Anti-inflammatory Properties of an Active Sesquiterpene Lactone and its Structure-Activity Relationship. Med chem 5:354-360. doi: 10.4172/2161-0444.1000286
Copyright: © 2015 Hu Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.