1-O-Tigloyl-1-O-deacetyl-nimbolinin B Inhibits LPS-Stimulated Inflammatory Responses by Suppressing NF-κB and JNK Activation in Microglia Cells

Abstract

Abstract. Overactivation of microglia may contribute to the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and HIV dementia. Thus, regulating microglial activation has been an important therapeutic strategy for treating neurodegenerative diseases. In this research, we compared three limonoids compounds extracted from Melia toosendan by a cell-based assay to investigate their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated microglia cells. Our study indicated that 1-O-tigloyl-1-O-deacetyl-nimbolinin B (TNB) markedly suppressed the production of nitric oxide (NO) and tumor necrosis factor (TNF)-a in LPS-stimulated microglia cells. TNB also inhibited the gene expression of inducible nitric oxide synthase (iNOS), TNF-a, cyclooxygenase (COX-2), and interleukin (IL)-1b. In addition, TNB inhibited generation of intracellular reactive oxygen species (ROS). We found that TNB significantly attenuated the nuclear translocation of NF-kB, inhibiting the activation of c-jun N-terminal kinase (JNK) in LPS-stimulated BV-2 cells. Furthermore, TNB reduced cytotoxicity of activated microglia toward HT-22 hippocampal cells in a co-culture system. Taken together, our experimental results reveal, for the first time, that TNB is a potent inhibitor of microglia-mediated inflammation, and it might be a potential candidate for the treatment of neurodegenerative diseases.

Activation of Nur77 in microglia attenuates proinflammatory mediators production and protects dopaminergic neurons from inflammation‐induced cell death

“…The standard curve of sodium nitrite (0–150 μM) was made as described before (Tao et al . ; Chen et al . ).…”

MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation

“…Therefore, we used cultured microglia to investigate the effects of let-7c-5p on microglia-m ediated neuroinflammation in vitro. Lipopolysaccharide (LPS), the major component of the walls of gram-negative bacteria, is a well-established activator of microglia/macrophages (Tao et al, 2014;Xu et al, 2015). We treated the BV2 microglial cell line and mouse primary microglia with LPS (200 ng/ml).…”

Inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity suppresses microglia‐mediated inflammatory responses

“…BV‐2 murine microglia cell line and HT‐22 mouse neuroblastoma cell line were cultured in complete Dulbecco's modified Eagle's medium (DMEM) containing 10% heat‐inactivated fetal bovine serum (FBS), penicillin (100 U/mL), and streptomycin (100 mg/mL) in a 37°C, 5% CO 2 incubator as previously described . For the transfection, BV2 cells were transfected with MIF siRNA by RNAIMAX reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions.…”