7-methoxyflavone and Inflammation

Endothelial cells (ECs) are vital regulators of inflammatory processes, there is the potential for inhibition of EC inflammation to be a therapeutic target in chronic inflammatory diseases. This study aimed to investigate the effect of 7-methoxyisoflavone (7-Mif) on endothelial inflammation. Our results showed that 7-Mif have no cytotoxicity on HUVECs. Pretreatment with 5 μM, 10 μM and 50 μM 7-Mif significantly reduced IL-1β-induced ICAM-1 (28.1% ± 4.1%, 25.9 ± 2.5% and 32.0% ± 3.2%, respectively) and VCAM-1 (48.0% ± 5.6%, 40.1 ± 3.1% and 39.6% ± 3.1%, respectively) mRNA expression. And pretreatment with 10 μM and 50 μM 7-Mif significantly reduced IL-1β-induced ICAM-1 (45.1% ± 4.4% and 33.6 ± 4.4%, respectively) and VCAM-1 (53.0% ± 3.7% and 53.7 ± 5.1%, respectively) protein levels. Furthermore, pretreatment with 50 μM 7-Mif inhibited monocyte-endothelial cell adhesion (50.2% ± 4.2%). Mechanistically, our results showed that 7-Mif reversed IL-1β-induced NF-κB activation and p65 translocation to the nucleus, therefore inhibiting endothelial cell inflammation. In addition, we confirmed that 7-Mif 10 mg/kg and 20 mg/kg reduced LPS-induced ICAM-1 (47.3% ± 1.3% and 39.0% ± 3.2%, respectively) and VCAM-1 (56.5 ± 2.8% and 47.8 ± 4.3%, respectively) expression and attenuated inflammatory injury in mice. In conclusion, we showed the inhibitory effect of 7-Mif on endothelial inflammation by suppressing the expression of endothelial adhesion molecules and monocyte adhesion. Our data illustrated that 7-Mif could positively regulate the process of endothelial inflammation.

Topics: Animals; Cell Adhesion; Cells, Cultured; Endothelial Cells; Flavones; Inflammation; Intercellular Adhesion Molecule-1; Lipopolysaccharides; Mice; NF-kappa B; RNA, Messenger; Vascular Cell Adhesion Molecule-1

Neuroprotective potential of 7-methoxyflavanone (7MF) and its underlying mechanism was investigated.. Inhibitory effects of 7MF on microglial activation and neuroinflammation were evaluated by employment of lipopolysaccharide (LPS)-induced BV2 microglial cells. Changes in expression of genes and proteins of interest were investigated by RT-qPCR analysis and Western blot analysis. Inhibitory effects of 7MF on microglial overactivation were verified in LPS-treated C57BL/6J mice using ionized calcium-binding adaptor molecule-1 (Iba1) in the brain and interleukin-6 (IL-6) in serum as indicators.. In BV2 cells, pretreatment with 7MF antagonized LPS-induced production of inflammatory factors IL-6, tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Mechanistic studies revealed reduced expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor-88 (MyD88), phosphorylated forms of c-Jun N-terminal kinase (p-JNK) and extracellular signal-regulated kinases 1/2 (p-ERK) but increased nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and cellular expression of NAD(P)H quinone dehydrogenase-1 (NQO-1) by 7MF. In LPS-treated mice, pretreatment with 7MF reduced the brain level of Iba1 and serum level of IL-6.. 7-methoxyflavanone inhibited LPS-stimulated TLR4/MyD88/MAPK signalling and activated Nrf2-mediated transcription of antioxidant protein NQO-1, showing antineuroinflammatory effect, so it is a potential neuroprotective agent.

Topics: Animals; Cell Line; Cell Survival; Cyclooxygenase 2; Extracellular Signal-Regulated MAP Kinases; Flavanones; Flavones; Inflammation; Inflammation Mediators; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Microglia; Mitogen-Activated Protein Kinase 3; Myeloid Differentiation Factor 88; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type II; Phosphorylation; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha