title: Genipin inhibits the inflammatory response of rat brain microglial cells.
abstract: Microglia are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of various disorders in traditional oriental medicine. Genipin has recently been reported to have diverse pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The specific aim of this study was to examine whether genipin represses brain microglial activation. Genipin was effective at inhibiting LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells. Genipin reduced the LPS-stimulated production of tumor necrosis factor-alpha, interleukin-1beta, prostaglandin E(2), intracellular reactive oxygen species, and NF-kappaB activation. In addition, genipin reduced NO release from microglia stimulated with interferon-gamma and amyloid-beta. Both pretreatment and post-treatment of genipin to LPS-stimulated microglia were effective at decreasing NO release. Furthermore, genipin effectively inhibited microglial activation in a mouse model of brain inflammation. These results suggest that genipin provide neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.
authors.affiliation: Department of Medical Science, Graduate School of East-West Medical Science; Kyung Hee University, Yongin-si 446-701, South Korea.
authors.forename: Kyong Nyon
authors.initials: KN
authors.lastname: Nam
authors.forename: Yo-Sup
authors.initials: YS
authors.lastname: Choi
authors.forename: Hoon-Ji
authors.initials: HJ
authors.lastname: Jung
authors.forename: Gun Hyuk
authors.initials: GH
authors.lastname: Park
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Park
authors.forename: Sang-Kwan
authors.initials: SK
authors.lastname: Moon
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Cho
authors.forename: Chulhun
authors.initials: C
authors.lastname: Kang
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
authors.forename: Eunjoo H
authors.initials: EH
authors.lastname: Lee
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007249:Inflammation / Q000473:pathology* / Q000517:prevention & control*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057889:Iridoid Glycosides; D039823:Iridoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000473:pathology; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007202:Indicators and Reagents; D057889:Iridoid Glycosides; D039823:Iridoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D017382:Reactive Oxygen Species; D007371:Interferon-gamma; C007834:genipin