LPS-induced iNOS expression in N9 microglial cells is suppressed by             geniposide via ERK, p38 and nuclear factor-κB signaling pathways.
Activated microglia producing reactive nitrogen species, inflammatory factors,             reactive oxygen species (ROS) and other neurovirulent factors, can lead to the             development of neurodegenerative diseases. Certain compounds can inhibit the activation             of microglia. However, the mechanisms remain unclear. In the present study, we             investigated the inhibitory effect of geniposide on the production of ROS and             inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated             N9 murine microglial cells through the p38, ERK1/2 and nuclear factor-κB (NF-κB)             signaling pathways. After the N9 cells were pre-treated with the vehicle or geniposide             and exposed to LPS for the time indicated, the MTT conversion test was used to             assess cell viability. Suitable concentrations were chosen and adjusted according             to the experiments. Extracellular nitric oxide (NO) release was measured by Griess             reaction. The formation of ROS and intracellular NO was evaluated by fluorescence             imaging. NOS activities were determined using commercially available kits. The             morphology of the N9 cells was examined by hematoxylin and eosin staining. The             expression of iNOS mRNA was examined by RT-PCR. The protein levels of iNOS, p38             mitogen-activated protein kinase (MAPK), ERK1/2 and NF-κB, inhibitory factor-κB-α             (IκB-α) were determined by western blot analysis. The results showed that geniposide             attenuated the activation of N9 cells and inhibited the overproduction of NO,             intracellular ROS and the expression of iNOS induced by LPS in the cells. In addition,             geniposide blocked the phosphorylation of p38, ERK1/2 and inhibited the drop-off             of IκB induced by LPS in the cells. These data indicate that geniposide has therapeutic             potential for the treatment of neurodegenerative diseases, and that it exerts             its effects by inhibiting inflammation.
Department of Pathology, Zhejiang Cancer Hospital, Zhejiang 310022,                     P.R. China.
Gu
G
Zhang
Jun-Lin
JL
He
Xiao-Yan
XY
Xie
Chao
C
Yu
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D039823:Iridoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016166:Free Radical Scavengers; D039823:Iridoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C007835:geniposide; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases