Effect of CO on nitrate/nitrite content (A) and xanthine oxidase activity (B) in ileum mucosa of endotoxin-injected mice.

<p>Mice received by gavage 6.5 mg/kg CO (endotoxin-COL), 13 mg/kg CO (endotoxin-COM), 26 mg/kg CO (endotoxin-COH), or vehicle (endotoxin-V) every other day 8 times followed by injection with endotoxin from <i>S</i>. <i>typhimurium</i> (i.p., 10 mg/kg body weight). Control mice were pretreated with vehicle (control-V) followed by injection with saline. Samples were collected 12 h after injection. Data are means ± SDs for six mice in each group. #Significantly different from the control (p < 0.05). a, b not sharing the same letter are significantly different (p < 0.05).</p

Peripheral Concentration of Nitrate/nitrite and Proinflammatory Cytokines of Control Mice or Endotoxin-Injected Mice That Did or Did Not Receive CO^a.

<p>^aValues are the mean ± SD for six mice per group.</p><p>control-V, control mice treated with vehicle; endotoxin-V, endotoxin-injected mice treated with vehicle; endotoxin-COL, endotoxin-injected mice treated with 6.5 mg/(kg bw) of CO; endotoxin-COM, endotoxin-injected mice treated with 13 mg/(kg bw) of CO; endotoxin-COH, endotoxin-injected mice treated with 26 mg/(kg bw) of CO.</p><p>#Significantly different from the control group (p < 0.05).</p><p>a, b, and c indicate the means within a row not sharing the same superscript letter are significantly different (p < 0.05).</p><p>Peripheral Concentration of Nitrate/nitrite and Proinflammatory Cytokines of Control Mice or Endotoxin-Injected Mice That Did or Did Not Receive CO^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120700#t002fn001" target="_blank">a</a>}.</p

Cross-sections of ileum stained with hematoxylin and eosin.

<p>Mice received by gavage 6.5 mg/kg CO (endotoxin-COL), 13 mg/kg CO (endotoxin-COM), 26 mg/kg CO (endotoxin-COH), or the vehicle (endotoxin-V) every other day 8 times followed by injection with endotoxin from <i>S</i>. <i>typhimurium</i> (i.p., 10 mg/kg body weight). Control mice were pretreated with vehicle (control-V) followed by injection with saline. Samples were collected at 12 h after injection. Original magnification x 100.</p

Tissue or Organ Weight to Body Weight Ratio of Control Mice or Endotoxin-Injected Mice That Did or Did Not Receive CO^a.

<p>^aValues are the mean ± SD for six mice per group.</p><p>control-V, control mice treated with vehicle; endotoxin-V, endotoxin-injected mice treated with vehicle; endotoxin-COL, endotoxin-injected mice treated with 6.5 mg/(kg bw) of CO; endotoxin-COM, endotoxin-injected mice treated with 13 mg/(kg bw) of CO; endotoxin-COH, endotoxin-injected mice treated with 26 mg/(kg bw) of CO.</p><p>#Significantly different from the control group (p < 0.05).</p><p>Tissue or Organ Weight to Body Weight Ratio of Control Mice or Endotoxin-Injected Mice That Did or Did Not Receive CO^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120700#t001fn001" target="_blank">a</a>}.</p

Effect of CO on NF-κB activation in ileum mucosa and in mesenteric lymph nodes of endotoxin-injected mice.

<p>Mice received by gavage 6.5 mg/kg CO (endotoxin-COL), 13 mg/kg CO (endotoxin-COM), 26 mg/kg CO (endotoxin-COH), or the vehicle (endotoxin-V) every other day 8 times followed by injection with endotoxin from <i>S</i>. <i>typhimurium</i> (i.p., 10 mg/kg body weight). Control mice were pretreated with vehicle (control-V) followed by injection with saline. Samples were collected at 12 h after injection. Data are means ± SDs for six mice in each group. #Significantly different from the control (p < 0.05). a, b, and c the same tissue not sharing the same letter are significantly different (p < 0.05).</p

Effect of CO on the expression of TLR4, MD2, and MyD88 in mesenteric lymph nodes (A) and in ileum mucosa (B) of endotoxin-injected mice.

<p>Mice received by gavage 6.5 mg/kg CO (endotoxin-COL), 13 mg/kg CO (endotoxin-COM), 26 mg/kg CO (endotoxin-COH), or the vehicle (endotoxin-V) every other day 8 times followed by injection with endotoxin from <i>S</i>. <i>typhimurium</i> (i.p., 10 mg/kg body weight). Control mice were pretreated with vehicle (control-V) followed by injection with saline. Samples were collected at 12 h after injection. Data are means ± SDs for three mice in each group. #Significantly different from the control (p < 0.05). a, b, and c not sharing the same letter are significantly different (p < 0.05).</p

Inhibition of TNF-α-Induced Inflammation by Andrographolide via Down-Regulation of the PI3K/Akt Signaling Pathway

Andrographolide (<b>1</b>), an active constituent of <i>Andrographis paniculata,</i> decreased tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule-1 (ICAM-1) expression and adhesion of HL-60 cells onto human umbilical vein endothelial cells (HUVEC), which are associated with inflammatory diseases. Moreover, <b>1</b> abolished TNF-α-induced Akt phosphorylation. Transfection of an activated Akt1 cDNA vector increased Akt phosphorylation and ICAM-1 expression like TNF-α. In addition, <b>1</b> and LY294002 blocked TNF-α-induced IκB-α degradation and nuclear p65 protein accumulation, as well as the DNA-binding activity of NF-κB. Compound <b>1</b> exhibits anti-inflammatory properties through the inhibition of TNF-α-induced ICAM-1 expression. The anti-inflammatory activity of <b>1</b> may be associated with the inhibition of the PI3K/Akt pathway and downstream target NF-κB activation in HUVEC cells