Understanding the mode of action of a pterostilbene derivative as anti-inflammatory agent

Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action. The newly developed compound was tested for its anti-inflammatory actions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced rat paw edema models. Our data showed that the derivative inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the downstream products like nitric oxide (NO) and PGE(2), at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of I kappa B-alpha and nuclear translocation of the p-NF kappa B p65. Moreover, inhibition of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In addition, the newly developed compound also reduced the paw edema, the tissue content of NO, PGE(2) and expression of iNOS and COX-2 proteins within the tissues after X-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemoprevenfive potential based on its stronger anti-NF kappa B and anti-inflammatory activities as compared to its natural counterpart, i.e., PTER. Thus, this compound can be used towards the development of an effective anti-inflammatory agent. (C) 2015 Elsevier B.V. All rights reserved.