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Isoorientin attenuates lipopolysaccharide-induced pro-inflammatory responses through down-regulation of ROS-related MAPK/NF-κB signaling pathway in BV-2 microglia

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Abstract

Isoorientin (ISO) is a flavonoid compound in the human diet, and has been known to possess various bioactivities. However, the effects of ISO on microglia inflammation have not been investigated. The current study investigates the neuroprotective effect of ISO in LPS-activated mouse microglial (BV-2) cells. ISO significantly increased the BV-2 cells viability, blocked the protein expression of inducible nitric oxide synthase and cyclooxygenase-2, and decreased the production of nitric oxide, pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-1β. The activation of mitogen-activated protein kinases (MAPKs) was blocked by ISO, and NF-κB nuclear translocation was decreased by ISO both alone and together with NF-κB inhibitor (PDTC) and MAPKs inhibitors (U0126, SP 600125, and SB 203580). Furthermore, ISO strongly quenched intracellular reactive oxygen species (ROS) generation. ROS inhibitor (N-acetyl cysteine, NAC) significantly inhibited pro-inflammatory cytokines release and NF-κB and MAPKs activation, indicating that ISO attenuated neuroinflammation by inhibiting the ROS-related MAPK/NF-κB signaling pathway.

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Abbreviations

BV-2 cell:

Mouse microglial cell line

ISO:

Isoorientin

LPS:

Lipopolysaccharide

ROS:

Reactive oxygen species

NO:

Nitric oxide

MAPKs:

Mitogen-activated protein kinases

NF-κB:

Nuclear factor κB

TNF-α:

Tumor necrosis factor

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

COX:

Cyclooxygenase

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Acknowledgments

This work was financially supported by the Young Scientists Fund of the National Natural Science Foundation of China (No. 31000757), and the National “Twelfth Five-Year” Plan for Science and Technology Support (No. 2012BAH30F03).

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The authors declare that there are no conflicts of interest.

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Correspondence to Xuebo Liu.

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Yuan, L., Wu, Y., Ren, X. et al. Isoorientin attenuates lipopolysaccharide-induced pro-inflammatory responses through down-regulation of ROS-related MAPK/NF-κB signaling pathway in BV-2 microglia. Mol Cell Biochem 386, 153–165 (2014). https://doi.org/10.1007/s11010-013-1854-9

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