Curcumenol isolated from Curcuma zedoaria suppresses Akt-mediated NF-κB activation and p38 MAPK signaling pathway in LPS-stimulated BV-2 microglial cells

Abstract

Curcumenol, a sesquiterpene isolated from Curcuma zedoaria is known to possess a variety of health and medicinal values which includes neuroprotection, anti-inflammatory, anti-tumor and hepatoprotective activities. The current study aim is to investigate the modulatory effects of curcumenol towards the lipopolysaccharides (LPS)-induced inflammation in BV-2 microglia. Curcumenol markedly decreased LPS-induced production of nitric oxide (NO), pro-inflammatory cytokines [(IL-6) and (TNF-α)] and pro-inflammatory proteins expression, iNOS and COX-2. Moreover, curcumenol inhibited NF-κB activation by suppressing the nuclear translocation of the NF-κB p65 subunit and blocking IκBα phosphorylation and degradation. Furthermore, an NF-κB inhibitor, ethyl 3,4-dihydroxycinnamate also known as caffeic acid ethyl ester (CAEE), attenuated LPS-stimulated iNOS and COX-2 expression, suggesting that NF-κB inhibition is a regulator in the expression of iNOS and COX-2 proteins. Further mechanistic study with an Akt inhibitor, triciribine hydrate (API-2), revealed that curcumenol acted through Akt-dependent NF-κB activation. Moreover, curcumenol inhibition on LPS-induced phosphorylation of p38 MAPK is confirmed by its inhibitor (SB 202190). These results indicate that curcumenol diminishes the proinflammatory mediators and the expression of the regulatory genes in LPS-stimulated BV-2 by inhibiting Akt-dependent NF-κB activation and downregulation of Akt and p38 MAPKs signaling.

Anti-neuroinflammatory Activity of Elephantopus scaber L. via Activation of Nrf2/HO-1 Signaling and Inhibition of p38 MAPK Pathway in LPS-Induced Microglia BV-2 Cells

“…Thus, most of the anti-inflammatory drugs were found to modulate iNOS and COX-2 via inhibit NF-κB and p38 signaling. For instance, resveratrol and curcumenol, natural plant derivatives, suppressed iNOS and COX-2 via inhibition of NF-κB and p38 signaling pathways (Zhong et al, 2012; Lo et al, 2015). This is concordant with our current findings which demonstrated that treatment with ESEAF suppressed the phosphorylation of p38 by attenuating the translocation of NF-κB along with the alteration of iNOS and COX-2 upon stimulation of LPS in microglia cells, suggesting that ESEAF is a potent inhibitor of p38.…”

Suppressive effects of Gua Lou Gui Zhi decoction on MCAO-induced NO and PGE2 production are dependent on the MAPK and NF-κB signaling pathways

“…Hyperactivated microglia produce large amounts of inflammatory molecules and promote neuronal death (13–15). Furthermore, microglial activation is correlated with sequential signaling pathways, including NF-κB and MAPK cascades, thus leading to the expression and production of proinflammatory mediators (16). …”

Fucoxanthinol from the Diatom Nitzschia Laevis Ameliorates Neuroinflammatory Responses in Lipopolysaccharide-Stimulated BV-2 Microglia

“…In response to inflammatory stimuli, IκB phosphorylation and degradation lead to the release of NF-κB dimers into the nucleus, thus expressing specific target genes, such as pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), and the cyclooxygenase-2 (COX-2) protein [7]. Moreover, the three mitogen-activated protein kinase (MAPK) signaling pathways consisting of c-Jun NH2-terminal kinase (JNK), p38 and extracellular signal-regulated kinase (ERK) also modulate microglial inflammatory responses through the regulation of downstream cellular targets, including NF-κB pathway [8]. In addition, the phosphatidyl inositol 3-kinase/Akt (PI3K/Akt) pathway plays an essential role in the activation of NF-κB and subsequent up-regulation of inflammatory genes expression [8,9].…”