Troxerutin attenuates LPS-induced inflammation in BV۲ microglial cells involving Nrf۲ activation and NF-κB pathway inhibition

Objective(s): 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 BV۲ microglia and explored its mechanism.Materials and Methods: To investigate the suppressive action of TX on M۱ polarization, BV۲ cells were stimulated with LPS and then treated with TX or minocycline (MINO). Cell viability was assessed via Cell Counting Kit-۸ (CCK-۸), and inflammatory cytokines were measured by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Furthermore, the nuclear factor erythroid ۲-related factor ۲ (Nrf۲)/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.  Results: TX inhibited the expression of interleukin-۶ (IL-۶) and interleukin-۱β (IL-۱β), as well as the secretion of IL-۶ and tumor necrosis factor-α (TNF-α). Additionally, TX accelerated the release of transforming growth factor-β (TGF-β) and cluster of differentiation ۲۰۶ (CD۲۰۶) in BV۲ 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 Nrf۲ and heme oxygenase-۱ (HO-۱) protein expression.Conclusion: TX suppresses pro-inflammatory induction after LPS stimulation of BV۲ microglia, which may be related to the NF-κB inhibition and accelerated HO-۱/Nrf۲ activation. These findings pinpoint the potential therapeutic potential of TX in inflammation-induced neurodegenerative diseases.

کلیدواژه ها:

Anti-inflammatory agents ، Lipopolysaccharides ، Microglia ، Neuroinflammation ، NF-kappa B ، NRF۲ transcription factor