Lutein suppresses inflammatory responses through Nrf2 activation and NF-κB inactivation in lipopolysaccharide-stimulated BV-2 microglia.

In this study, the effects of lutein on neuroinflammation in lipopolysaccharide (LPS)-activated BV-2 microglia were investigated. The production of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and nitric oxide was measured in culture medium using enzyme immunoassay and Griess reagent, respectively. The expression of proteins was determined using Western blot. Pretreatment with lutein (50 μM) prior to LPS (1 μg/mL, 12 h) stimulation resulted in a significant inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression, as well as tumor necrosis factor-α, interleukin-1β, and nitric oxide production (p < 0.05). Further experiments demonstrated that lutein suppressed LPS-induced NF-κB activation by inhibiting the phosphorylation of p38 kinase, c-Jun N-terminal kinase (JNK), and Akt kinase (p < 0.05). Moreover, lutein markedly quenched reactive oxygen species and promoted antioxidant protein expression including heme oxygenase-1 and quinone oxidoreductase by enhancing the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mediated NF-E2-related factor 2 (Nrf2) activation (p < 0.05). These results suggest that lutein attenuates neuroinflammation in LPS-activated BV-2 microglia partly through inhibiting p38-, JNK-, and Akt-stimulated NF-κB activation and promoting ERK-induced Nrf2 activation, suggesting that lutein has great potential as a nutritional preventive strategy in inflammation-related neurodegenerative disorders.

Wu W ，Li Y ，Wu Y ，Zhang Y ，Wang Z ，Liu X ... -  《-》

Micheliolide suppresses LPS-induced neuroinflammatory responses.

Sun Z ，Li G ，Tong T ，Chen J ... -  《PLoS One》

Antimalarial Drug Artemether Inhibits Neuroinflammation in BV2 Microglia Through Nrf2-Dependent Mechanisms.

Okorji UP ，Velagapudi R ，El-Bakoush A ，Fiebich BL ，Olajide OA ... -  《-》

Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells.

Zhong LM ，Zong Y ，Sun L ，Guo JZ ，Zhang W ，He Y ，Song R ，Wang WM ，Xiao CJ ，Lu D ... -  《PLoS One》

Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-κB/activator protein-1 signaling pathways: a possible role in atherosclerosis.

Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25-200μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE2 production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease.

Hseu YC ，Senthil Kumar KJ ，Chen CS ，Cho HJ ，Lin SW ，Shen PC ，Lin CW ，Lu FJ ，Yang HL ... -  《-》