title: Direct interaction of garcinol and related polyisoprenylated benzophenones of Garcinia cambogia fruits with the transcription factor STAT-1 as a likely mechanism of their inhibitory effect on cytokine signaling pathways.
abstract: Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1-3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in KD values in the micromolar range. Consistent with the observed high affinity toward the STAT-1 protein, garcinol and guttiferones K and M were able to modulate cytokine signaling in different cultured cell lines, mainly by inhibiting STAT-1 nuclear transfer and DNA binding, as assessed by an electrophorectic mobility shift assay.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno , Via Giovanni Paolo II n.132, I-84084 Fisciano (SA), Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Masullo
authors.forename: Marta
authors.initials: M
authors.lastname: Menegazzi
authors.forename: Simone
authors.initials: S
authors.lastname: Di Micco
authors.forename: Pascale
authors.initials: P
authors.lastname: Beffy
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Martina
authors.initials: M
authors.lastname: Dal Bosco
authors.forename: Michela
authors.initials: M
authors.lastname: Novelli
authors.forename: Cosimo
authors.initials: C
authors.lastname: Pizza
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Masiello
authors.forename: Sonia
authors.initials: S
authors.lastname: Piacente
mesh_terms: D001577:Benzophenones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015152:Blotting, Northern; D005260:Female; D005638:Fruit / Q000737:chemistry; D029761:Garcinia cambogia / Q000737:chemistry*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008968:Molecular Conformation; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013188:Sri Lanka; D013729:Terpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D001577:Benzophenones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D013729:Terpenes; C501151:guttiferone I; C519762:guttiferone K; C054597:garcinol