Document Detail


Geniposide Reduces Inflammatory Responses of Oxygen-Glucose Deprived Rat Microglial Cells via Inhibition of the TLR4 Signaling Pathway.
MedLine Citation:
PMID:  22869019     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Geniposide, an iridoid glycoside isolated from Gardenia, has neuroprotective activities against oxidative stress and inflammation. The present study investigated the in vivo protective effect of geniposide on ischemia/reperfusion-injured rats by middle cerebral artery occlusion (MCAO), and the inhibitory effects of geniposide and mechanisms against activation of microglial cells by oxygen-glucose deprivation (OGD) in vitro. Male SD rats were subjected to treatment with geniposide at 15, 30 and 60 mg/kg immediately after MCAO. Cerebral infarct volume and microglial cell activation were assessed following 24 h reperfusion. Cultured primary rat microglial cells were exposed to geniposide at the concentrations of 12.5, 25 and 50 μg/mL during 4 h of OGD. The effects of geniposide were evaluated in terms of (1) cell viability; (2) secretion of TNF-α, IL-1β, IL-6, IL-8 and IL-10 into culture media; (3) TLR4 mRNA expression; (4) protein expression of TLR4, p-ERK1/2, p-IκB, p-p38, nuclear and cytoplasmic fraction NF-κB p65; and (5) nuclear transfer of NF-κB p65. Geniposide reduced the infarct volume and inhibited the activation of microglial cells in ischemic penumbra in vivo. OGD increased cell viability and release of TNF-α, IL-1β, IL-6, IL-8 and IL-10, these effects were suppressed by geniposide. Geniposide also attenuated the increases in the OGD-induced TLR4 mRNA and protein levels. In addition, geniposide at 25 and 50 μg/mL downregulated the phosphorylation of ERK, IκB and p38, as well as inhibited nuclear transcriptional activity triggered via NF-κB p65 in microglial cells by OGD. In conclusion, geniposide displays a neuroprotective effect on ischemia/reperfusion-injured rats in vivo and inhibits OGD-induced activation of microglial cells by attenuating inflammatory factors and NF-κB activation in vitro.
Authors:
Jun Wang; Jincan Hou; Peng Zhang; Dan Li; Cuixiang Zhang; Jianxun Liu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-7
Journal Detail:
Title:  Neurochemical research     Volume:  -     ISSN:  1573-6903     ISO Abbreviation:  Neurochem. Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute of Basic Theory, China Academy of Chinese Medical Sciences, 16 Dong Zhi Men Nei Nan Xiao Jie, Dong Cheng District, Beijing, 100700, China.
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