Fig. 3

Zerumbone attenuates mitogen-activated protein kinase activation in microglial cells. a Bar graph showing the concentration of prostaglandin E2 (PGE2) in N9 cells. The production of PGE2 was significantly reduced by zerumbone. b Representative western blots and a bar graph showing the protein expression of cyclooxygenase-2 (Cox-2) in N9 cells. The production of Cox-2 was significantly reduced by zerumbone. c Representative western blots and a bar graph showing the protein expression of microsomal prostaglandin E synthase-1 (mPGES-1) in N9 cells. The production of mPGES-1 was significantly reduced by zerumbone. d Representative western blots and a bar graph showing the protein expression levels of p-extracellular signal-regulated kinase (p-ERK), ERK, p-p38, p38, p-IκBα, IκBα, p-p65, and p65 in N9 cells. Zerumbone treatment significantly decreased the levels of p-ERK, p-p38, p-IκBα, and p-p65. e Zerumbone inhibited the translocation of nuclear factor-kappa B (NF-κB) from the cytosol to the nucleus in N9 cells treated with Aβ for 24 h. f The concentrations of cytokines (interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10)) in the cell culture supernatants of N9 microglia. Zerumbone, U0126, SB202190, and BAY 11-7082 blocked the Aβ induced up-regulation of IL-1β and TNF-α production. The Aβ-induced decrease in IL-10 production was also reversed by zerumbone, U0126, SB202190, and BAY 11-7082. Data are presented as median and interquartile ranges (n = 4). Zer1, 3, 10 = zerumbone concentrations of 1, 3, or 10 μg/ml. U, U0126 (an ERK inhibitor); SB, SB202190 (a p38 inhibitor); BAY, BAY 11–7082 (an NF-κB inhibitor). g, h Primary microglia were isolated from the cortex of vehicle- and zerumbone-treated APP/PS1 mice. The microglia isolated from zerumbone-treated mice exhibited decreased protein levels of p-ERK1/2, p-p38, p-IκBα, and p-p65 compared to vehicle-treated mice. Data are presented as median and interquartile ranges (n = 3). *p < 0.05, **p < 0.01