Attenuation of inflammatory-mediated neurotoxicity by Saururus chinensis extract in LPS-induced BV-2 microglia cells via regulation of NF-κB signaling and anti-oxidant properties

Abstract

BackgroundA Saururus chinensis Baill (SC) has been used by Native Americans, early colonists and practitioners of Korean traditional medicine for treating several diseases including cancer, rheumatoid arthritis and edema. The objective of this study was to evaluate the effects of SC extract in lipopolysaccharide (LPS)-stimulated neuroinflammatory responses in BV-2 microglial cells.MethodsThe effects of SC on the LPS–induced neuroinflammatory responses in BV-2 microglial cells were assessed by Western blotting, RT-PCR and immunofluorescence labeling techniques. DPPH and alkyl radical scavenging assay was performed to evaluate the anti-oxidant effects. Comparisons between groups were analyzed using one-way analysis of variance followed by Dunnett’s multiple comparisons test using GraphPad Prism V5.01 software.ResultsPre-treatment with SC extract (1, 5 and 10 μg/mL) significantly (p < 0.001 at 10 μg/mL) and concentration dependently inhibited LPS-induced production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) and suppressed the inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin (IL)-6 in BV-2 microglial cells (p < 0.001 at 10 μg/mL). Further, SC suppressed the nuclear factor-kappa B (NF-κB) activation by blocking the degradation of IκB-α. SC also exhibited profound anti-oxidant effects by scavenging 1, 1-diphenyl-2-picrylhydrazyl (DPPH) (IC50: 0.055 mg/mL) and alkyl radicals (IC50: 0.349 mg/mL). High performance liquid chromatography finger printing analysis of SC revealed quercetin (QCT) as one of the major constituents compared with reference standard. QCT also inhibited the excessive release of NO, and inhibited the increased expressional levels of IL-6, iNOS and COX-2 in LPS-stimulated BV-2 cells.ConclusionsOur results indicated that SC inhibited the LPS-stimulated neuroinflammatory responses in BV-2 microglia via regulation of NF-κB signaling. The antioxidant active constituents of SC might be partly involved in delivering such effects. Based on the traditional claims and our present results SC can be potentially used in treating inflammatory-mediated neurodegenerative diseases.

Effects of Paeonol on Anti-Neuroinflammatory Responses in Microglial Cells

“…Microglia is the vital element of the brain immune surveillance and the defense function in the brain [ 33 , 34 , 35 ]. Microglia are sensitive to external environment stimulation, and numerous reports showed that microglia immediately react to pathogenic stimuli by increasing the expression of innate inflammatory mediators [ 36 ]. Excessive inflammatory response has been found to be responsible for several neurodegenaerative diseases [ 36 ].…”

“…Microglia are sensitive to external environment stimulation, and numerous reports showed that microglia immediately react to pathogenic stimuli by increasing the expression of innate inflammatory mediators [ 36 ]. Excessive inflammatory response has been found to be responsible for several neurodegenaerative diseases [ 36 ]. It is believed that microglia may play a role contributing to this process.…”

Aspirin down Regulates Hepcidin by Inhibiting NF-κB and IL6/JAK2/STAT3 Pathways in BV-2 Microglial Cells Treated with Lipopolysaccharide

“…Production of NO was assayed by measuring the levels of nitrite (a metabolite of NO) in the culture medium using a colorimetric assay with Griess reagent according to Kim et al [44], After 24 h of treatment with LPS with or without ASA, the culture media were collected and reacted with an equal volume of Griess reagent in 96-well culture plates and were incubated at room temperature for 10 min in the dark. The absorbance was measured at 540 nm using a microplate reader, and nitrite concentrations were calculated by reference to a standard curve generated by known concentrations of sodium nitrite.…”

Neuroprotective Effects of Quercetin in Alzheimer’s Disease

“…Reducing the neuroinflammatory events in microglia might afford a beneficial strategy for the prevention of the progression of inflammatory-mediated neurodegenerative disorders. Quercetin has been reported to have anti-inflammatory actions, and is a suitable candidate among phytochemicals for future studies on its efficacy to reverse neuroinflammation [135,136]. Quercetin has already been shown to inhibit neuroinflammation by reducing nitric oxide production, iNOS gene expression in microglia, the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), IFN-γ, interleukin-1β (IL-1β), IL-6, IL-12, and COX-2 in activated macrophages, as well as a reduction in cytokine expression as reported from in vivo studies.…”