Anti-inflammatory potential of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol in lipopolysaccharide-stimulated BV2 microglia.

ABSTRACT

In this study, we investigated the anti-inflammatory effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) in lipopolysaccharide (LPS)-stimulated BV2 microglia and the subsequent signaling events. Following stimulation with LPS, elevated production of nitric oxide (NO) and prostaglandin E2 (PGE2) was detected in BV2 cells; however, SMBD pretreatment inhibited the production of NO and PGE2 through suppressing gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, at non-toxic concentrations. LPS-stimulated gene expression and production of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were also significantly reduced by SMBD. The anti-inflammatory effects of SMBD were associated with suppression of LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB), and phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, a phosphatidylinositol 3-kinase (PI3K) downstream effector. Therefore, the present results demonstrate that SMBD down-regulates inflammatory gene expression by inhibiting the activation of NF-κB through interference with the activation of MAPKs and PI3K/Akt signaling. Taken together, our data suggest that SMBD may have potential to be developed into an effective anti-inflammatory agent.