Geniposide reduces inflammatory responses of oxygen-glucose deprived rat microglial cells via inhibition of the TLR4 signaling pathway.

Abstract

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
• Journal: Neurochemical research (Neurochem Res) Vol. 37 Issue 10 Pg. 2235-48 (Oct 2012) ISSN: 1573-6903 [Electronic] United States
• PMID: 22869019 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media
• Cytokines
• Iridoids
• Toll-Like Receptor 4
• geniposide
• Glucose
• Oxygen

Topics

• Animals
• Culture Media
• Cytokines (metabolism)
• Dose-Response Relationship, Drug
• Glucose (metabolism)
• Inflammation (metabolism, prevention & control)
• Iridoids (pharmacology)
• Male
• Microglia (drug effects, metabolism)
• Oxygen (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)