title: Understanding the mode of action of a pterostilbene derivative as anti-inflammatory agent.
abstract: 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 PGE2, at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of IκB-α and nuclear translocation of the p-NFκB 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, PGE2 and expression of iNOS and COX-2 proteins within the tissues after λ-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemopreventive potential based on its stronger anti-NFκB 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.
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Kumar
authors.initials: K
authors.lastname: Nikhil
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Sharan
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Srinivasa Rao
authors.initials: SR
authors.lastname: Palla
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Sham M
authors.initials: SM
authors.lastname: Sondhi
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Rama Krishna
authors.initials: RK
authors.lastname: Peddinti
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India. Electronic address: paroyfbs@iitr.ernet.in.
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002351:Carrageenan; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005528:Foot / Q000473:pathology; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D000067996:RAW 264.7 Cells; D051381:Rats; D013267:Stilbenes / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000235:genetics; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D013267:Stilbenes; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; C107773:pterostilbene; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: Anti-inflammatory; Carrageenan; Lipopolysaccharide; NFκB; Pterostilbene derivative; RAW 264.7 macrophage