title: Bresol inhibits phosphodiesterase 4 gene expression and modulates the levels of select mediators of inflammation in human monocytic cells.
abstract: Bresol-a poly-herbal formulation, has been reported to be effective against bronchial asthma and allergic rhinitis in children. In vivo studies have supported the anti-histaminic and anti-anaphylactic action of bresol. However, the mechanism of action of bresol in modulation of inflammation has not been studied at the cellular and molecular level. The present study was aimed to elucidate the mechanism(s) of action of bresol at the cellular and molecular levels, using human monocyte leukemia cells. The effects of bresol on phosphodiesterase 4B (PDE4B) gene expression were analyzed using human monocytic U937 leukemia cells. The ability of bresol to stimulate cAMP formation in these cells, as well as its effects on mediators of inflammation like tumor necrosis factor-α (TNFα), nitric oxide (NO), and cycloxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated U937 cells, were also studied. The results here indicated that bresol exhibited potential anti-inflammatory properties by inhibiting LPS-induced PDE4B gene expression in the cells. Bresol also dose dependently activated cAMP formation, and inhibited TNFα, NO, as well as COX-2 formation in the LPS-stimulated cells. Based upon the results, we concluded that the reported anti-inflammatory activity of bresol might be attributed to its abilities to inhibit PDE4B and thus elevate cAMP levels in human monocytes. The anti-inflammatory effects of bresol might also be a result of the capacity of bresol to modulate the formation of TNFα, NO, and COX-2 in monocytes.
authors.affiliation: Department of Cell biology and Immunology, Research and Development, The Himalaya Drug Company, Bangalore, India. sandeepravivarma@indiatimes.com
authors.forename: R
authors.initials: R
authors.lastname: Sandeep Varma
authors.forename: G
authors.initials: G
authors.lastname: Ashok
authors.forename: S
authors.initials: S
authors.lastname: Vidyashankar
authors.forename: K S
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: P S
authors.initials: PS
authors.lastname: Patki
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D058988:Phosphodiesterase 4 Inhibitors / Q000633:toxicity*; D028321:Plant Preparations / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
chemical_list: C570562:Bresol; D005562:Formazans; D018836:Inflammation Mediators; D058988:Phosphodiesterase 4 Inhibitors; D028321:Plant Preparations; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha; C079782:MTT formazan; D009569:Nitric Oxide; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4