Regulation of Microglia Activity by Glaucocalyxin-A: Attenuation of Lipopolysaccharide-Stimulated Neuroinflammation through NF-κB and p38 MAPK Signaling Pathways

Abstract

Microglial cells are the resident macrophages and intrinsic arm of the central nervous system innate immune defense. Microglial cells become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Therefore, regulating microglial activation may have therapeutic benefits that lead to alleviating the progression of inflammatory-mediated neurodegeneration. In the present study, we investigated the effect of glaucocalyxin A (GLA) isolated from Rabdosia japonica on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated primary microglia and BV-2 cells. GLA significantly inhibited LPS-induced production of nitric oxide and reversed the morphological changes in primary microglia. Further, GLA suppressed expression of inducible nitric oxide synthase and cyclooxygenase-2 dose-dependently at the mRNA and protein levels. The production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL)-1β, and IL-6 were inhibited by suppressing their transcriptional activity. Furthermore, GLA suppressed nuclear factor-κB activation by blocking degradation of IκB-α and inhibited the induction of lipocalin-2 expression in LPS-stimulated BV-2 cells. Mechanistic study revealed that the inhibitory effects of GLA were accompanied by blocking the p38 mitogen activated protein kinase signaling pathway in activated microglia. In conclusion, given that microglial activation contributes to the pathogenesis of neurodegenerative diseases, GLA could be developed as a potential therapeutic agent for treating microglia-mediated neuroinflammatory diseases.

Propofol attenuates intermittent hypoxia induced up-regulation of proinflammatory cytokines in microglia through inhibiting the activation of NF-Bκ/p38 MAPK signalling

“…Among these, p38 MAPK acts as a crucial regulator for the production of NF-κB-mediated proinflammatory cytokines and other mediators [15]. Glaucocalyxin A (GLA) can inhibit pro-inflammatory cytokines expression in microglial cells through NF-κB and p38 MAPK signalling pathways [14]. A recent report clarified that triroside attenuated the neuroinflammation in microglia via NF-κB and p38 MAPK signalling pathways [28].…”

A novel synthetic compound MCAP suppresses LPS-induced murine microglial activation in vitro via inhibiting NF-kB and p38 MAPK pathways

“…Additionally, we only included the primary microglia results concerning cell viability, cell morphology and NO production because they also might reflect the result of our compound in an animal study. However, due to time constraints and cell availability, we decided to carry out the rest of the experiments in the BV2 cells [15,28] . We observed that MCAP satisfactorily inhibited the mRNA expressions of TNF-α, IL-1β and IL-6, with the most significant inhibition at 1 and 10 μmol/L for TNF-α and IL-6 secretion.…”

“…Finally, the primary microglia cultures were grown and maintained in DMEM supplemented with 10% FBS and P-S. The BV2 microglia cells were acquired as described previously [15] . The BV2 cells were cultured in DMEM supplemented with 5% FBS and 100 U/mL P-S and maintained in a humidified incubator in an atmosphere of 5% CO 2 .…”

Glaucocalyxin A Activates FasL and Induces Apoptosis Through Activation of the JNK Pathway in Human Breast Cancer Cells

“…Rabdosia japonica (R. japonica) is a perennial herb that is distributed widely in East Asia, and the entire R. japonica extract has been used traditionally as a folk medicine for treating gastrointestinal disorders, tumors, and inflammatory diseases (Sun et al, 2006;Hong et al, 2008;Kim et al, 2013). In this study, the anti-cancer effect of Glaucocalyxin A (GLA) and the underlying mechanisms involved were investigated in breast cancer cells.…”