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Biochim Biophys Acta. 2014 Dec;1840(12):3311-9. doi: 10.1016/j.bbagen.2014.08.008. Epub 2014 Aug 23.

Tiliroside, a dietary glycosidic flavonoid, inhibits TRAF-6/NF-κB/p38-mediated neuroinflammation in activated BV2 microglia.

Author information

1
Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom.
2
Department of Chemistry, Faculty of Science, Obafemi Awolowo University, Ile-Ife, Nigeria.
3
Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom. Electronic address: o.a.olajide@hud.ac.uk.

Abstract

BACKGROUND:

Tiliroside is a dietary glycosidic flavonoid which has shown in vivo anti-inflammatory activity. This study is aimed at evaluating the effect of tiliroside on neuroinflammation in BV2 microglia, and to identify its molecular targets of anti-neuroinflammatory action.

METHODS:

BV2 cells were stimulated with LPS+IFNγ in the presence or absence of tiliroside. TNFα, IL-6, nitrite and PGE2 production was determined with ELISA, Griess assay and enzyme immunoassay, respectively. iNOS, COX-2, phospho-p65, phospho-IκBα, phospho-IKKα, phospho-p38, phospho-MK2, phosopho-MKK3/6 and TRAF-6 were determined by western blot analysis. NF-κB activity was also investigated using a reporter gene assay in HEK293 cells. LPS-induced microglia ROS production was tested using the DCFDA method, while HO-1 and Nrf2 activation was determined with western blot.

RESULTS:

Tiliroside significantly suppressed TNFα, IL-6, nitrite and PGE2 production, as well as iNOS and COX-2 protein expression from LPS+IFNγ-activated BV2 microglia. Further mechanistic studies showed that tiliroside inhibited neuroinflammation by targeting important steps in the NF-κB and p38 signalling in LPS+IFNγ-activated BV2 cells. This compound also inhibited LPS-induced TRAF-6 protein expression in BV2 cells. Antioxidant activity of tiliroside in BV2 cells was demonstrated through attenuation of LPS+IFNγ-induced ROS production and activation of HO-1/Nrf2 antioxidant system.

CONCLUSIONS:

Tiliroside inhibits neuroinflammation in BV2 microglia through a mechanism involving TRAF-6-mediated activation of NF-κB and p38 MAPK signalling pathways. These activities are possibly due, in part, to the antioxidant property of this compound.

GENERAL SIGNIFICANCE:

Tiliroside is a potential novel natural compound for inhibiting neuroinflammation in neurodegenerative disorders.

KEYWORDS:

Antioxidant; NF-κB; Neuroinflammation; TRAF-6; Tiliroside; p38

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