title: 2-Methyl-pyran-4-one-3-O-β-D-glucopyranoside isolated from leaves of Punica granatum inhibits the TNFα-induced cell adhesion molecules expression by blocking nuclear transcription factor-κB (NF-κB).
abstract: Here, we report bioactivity-guided isolation, purification and characterization of a novel compound, 2-methyl-pyran-4-one-3-O-β-d-glucopyranoside (MPG) from the leaves of Punica granatum. The structure of MPG was established on the basis of its detailed spectral analyses. We demonstrated that MPG not only inhibited the expression of cell adhesion molecules but also significantly blocked its functional consequence, that is, the adhesion of neutrophils on human endothelial cells monolayer. To elucidate the molecular mechanism of action of MPG, we showed that MPG decreased the transcript levels of ICAM-1, VCAM-1 and E-selectin genes. Using electrophoretic mobility shift assay (EMSA) and western blot analyses, we demonstrated that MPG significantly blocked both the TNFα-induced translocation and activation of nuclear transcription factor-κB (NF-κB). Thus, MPG could be useful as a novel lead molecule for developing future anti-inflammatory agents.
authors.affiliation: Institute of Genomics & Integrative Biology (Unit of C.S.I.R.), Mall Road, Delhi 110 007, India.
authors.forename: Sakshi
authors.initials: S
authors.lastname: Balwani
authors.forename: Debkumar
authors.initials: D
authors.lastname: Nandi
authors.forename: Parasuraman
authors.initials: P
authors.lastname: Jaisankar
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry*; D020714:Maximum Tolerated Dose; D008968:Molecular Conformation; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000378:metabolism; D010936:Plant Extracts; D018515:Plant Leaves / Q000737:chemistry*; D021381:Protein Transport / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014470:Umbilical Cord / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C560920:2-methyl-pyran-4-one-3-O-beta-D-glucopyranoside; D015815:Cell Adhesion Molecules; D003603:Cytotoxins; D019040:E-Selectin; D005960:Glucosides; D016328:NF-kappa B; D010936:Plant Extracts; C546936:SELE protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1