title: Genipin inhibits MMP-1 and MMP-3 release from TNF-a-stimulated  human periodontal ligament cells.
abstract: Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of inflammatory diseases in traditional oriental medicine. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify matrix metalloproteinase (MMP)-1 and MMP-3, which are related to the destruction of periodontal tissues in periodontal lesion, expression in tumor necrosis factor (TNF)-α-stimulated human periodontal ligament cells (HPDLCs). Genipin prevented TNF-α-mediated MMP-1 and MMP-3 productions in HPDLCs. Moreover, genipin could suppress not only extracellular signal-regulated kinase (ERK) and Jun-N-terminal kinase (JNK) phosphorylations but also AMP-activated protein kinase (AMPK) phosphorylation in TNF-α-stimulated HPDLCs. Inhibitors of ERK and AMPK could inhibit both MMP-1 and MMP-3 productions. Moreover, we revealed the ERK inhibitor suppressed AMPK phosphorylation in TNF-α-stimulated HPDLCs. These data provide a new mechanism through which genipin could be used for the treatment of periodontal disease to prevent MMPs expression in periodontal lesion.
authors.forename: Satoru
authors.initials: S
authors.lastname: Shindo
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Hosokawa
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D039823:Iridoids / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005419:Flavonoids; D039823:Iridoids; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C007834:genipin; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one