Acetylsalicylic Acid Accelerates The Viability Of Lfuoxetine On Lipopolysaccharide-induced BV-2Microglia Cells And Its Underlying Mechanism

The latest advancement in neurobiological research provided increasing evidencesthat inflammatory and neurodegenerative pathways play a relevant role in depression.According to the cytokine hypothesis, depression would be due to a stress-relatedincreased production of pro-inflammatory cytokines by the microglial activation. Thelipopolysaccharide (LPS) induced IDO, which would give rise to lower plasma TRPproduction and the increased synthesis production of detrimental tryptophan catabolites,such as QA, KYN, all of them would lead to the depression.Thus, using the BV-2microglial cell line, the aim of the present study was toinvestigate whether the co-administration of fluoxetine (FLX) and acetylsalicylic acid(ASA) could inhibit the microglial activation with the potential for additional benefit.Our results showed that FLX could inhibit LPS-induced production of IL-1β, theIDO enzyme and the depletion of TRP was also attenuated by FLX. Moreover, FLXcould inhibit phosphorylation of nuclear factor-κB (NF-κB), and the phosphorylation ofp38mitogen-activated protein kinase (MAPK), and the combined used of ASA could enhance the effect. Notably, the adjunctive agent ASA could also inhibitphosphorylation of extracellular regulated kinase1/2(ERK1/2). Taken together, ourresults suggest that fluoxetine may have some anti-inflammatory effect by modulatingmicroglial activation and ASA served as an effective adjunctive agent enhanced thetherapeutic effects.