Troxerutin attenuates LPS-induced inflammation in BV2 microglial cells involving Nrf2 activation and NF-κB pathway...

Microglial cell-mediated neuroinflammation is a key driver of central nervous system (CNS) homeostasis and a significant risk factor for neurodegeneration and development of neurological diseases. We assessed whether troxerutin (TX) exerts anti-neuroinflammatory effects in lipopolysaccharide (LPS)-stimulated BV2 microglia and explored its mechanism.

To investigate the suppressive action of TX on M1 polarization, BV2 cells were stimulated with LPS and then treated with TX or minocycline (MINO). Cell viability was assessed via Cell Counting Kit-8 (CCK-8), and inflammatory cytokines were measured by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Furthermore, the nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling pathway was analyzed by Western blotting (WB) to elucidate the molecular mechanism of the anti-neuroinflammatory activity of TX.

TX inhibited the expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β), as well as the secretion of IL-6 and tumor necrosis factor-α (TNF-α). Additionally, TX accelerated the release of transforming growth factor-β (TGF-β) and cluster of differentiation 206 (CD206) in BV2 microglia exposed to LPS. TX regulated the neuroinflammatory response by blocking phosphorylation of NF-κB and inhibitor of kappa B alpha (IκBα) mediated by LPS stimulation and inducing Nrf2 and heme oxygenase-1 (HO-1) protein expression.

TX suppresses pro-inflammatory induction after LPS stimulation of BV2 microglia, which may be related to the NF-κB inhibition and accelerated HO-1/Nrf2 activation. These findings pinpoint the potential therapeutic potential of TX in inflammation-induced neurodegenerative diseases.