BACKGROUND AND PURPOSEKaempferol, a dietary flavonoid and phyto-oestrogen, is known to have anti-inflammatory properties. Microglial activation has been implicated in various neurodegenerative diseases. Anti-inflammatory effects of kaempferol and the underlying mechanisms were investigated by using LPS-stimulated microglial BV2 cells. EXPERIMENTAL APPROACHCell viability was measured using MTT and neutral red assays. ELISA, Western blot, immunocytochemistry and electrophoretic mobility-shift assay were used to analyse NO, PGE2, TNF-a and IL-1b production, inducible NOS (iNOS), COX-2 expression and the involvement of signalling pathways such as toll-like receptor-4 (TLR4), MAPK cascades, PKB (AKT) and NF-kB. Accumulation of reaction oxygen species (ROS) was measured by nitroblue tetrazolium and 2′7′-dichlorofluorescein diacetate assay. Matrix metalloproteinase activity was investigated by zymography and immunoblot assay. Phagocytotic activity was assessed by use of latex beads. KEY RESULTSKaempferol significantly attenuated LPS-induced NO, PGE2, TNF-a, IL-1b and ROS production and phagocytosis in a concentration-dependent manner. Kaempferol suppressed the expression of iNOS, COX-2, MMP-3 and blocked the TLR4 activation. Moreover, kaempferol inhibited LPS-induced NF-kB activation and p38 MAPK, JNK and AKT phosphorylation. CONCLUSION AND IMPLICATIONSKaempferol was able to reduce LPS-induced inflammatory mediators through the down-regulation of TLR4, NF-kB, p38 MAPK, JNK and AKT suggesting that kaempferol has therapeutic potential for the treatment of neuroinflammatory diseases. AbbreviationsAKT, PKB; iNOS, inducible NOS; ROS, reactive oxygen species; TLR-4, toll-like receptor-4 (TLR4) BJP British Journal of Pharmacology