Luteolin Reduces Lipopolysaccharide-induced Lethal Toxicity and Expression of Proinflammatory Molecules in Mice

Abstract

Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)- induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, 32 mg/kg, intraperitoneally) exhibited high mortality with only 4.1% of the animals surviving seven days after the LPS challenge. On the contrary, mice that had received luteolin (0.2 mg/kg, intraperitoneally) before LPS showed an increased survival rate with 48% remaining alive on Day 7. To investigate the mechanism by which luteolin affords protection against LPS toxicity we measured intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-alpha) production in response to LPS in the presence or absence of luteolin pretreatment. Treatment of animals with LPS increased serum TNF-alpha levels in a time-dependent manner. The increase in peak serum TNF-alpha levels was sensitive to luteolin pretreatment. Luteolin pretreatment also reduced LPS-stimulated ICAM-1 expression in the liver and abolished leukocyte infiltration in the liver and lung. We conclude that luteolin protects against LPS-induced lethal toxicity, possibly by inhibiting proinflammatory molecule (TNF-alpha, ICAM-1) expression in vivo and reducing leukocyte infiltration in tissues.

Inhibitory effect of luteolin on osteoclast differentiation and function

“…According to Comalada et al (2006), luteolin is able to stimulate the expression of the antiinflammatory cytokine IL-10. In addition, luteolin inhibits LPS-induced IjB phosphorylation and TNFa secretion by macrophages in vitro and has antiinflammatory activities in mice (Kim and Jobin 2005;Kotanidou et al 2002). In contrast to these findings, our results showed that luteolin had no inhibitory effects on IjB signal expression.…”

Anti-inflammatory effects of luteolin on experimental autoimmune thyroiditis in mice

“…Therefore, it is theoretically reasonable to target IL-6/STAT3 to intervene in the early stage of autoimmune thyroiditis in order to explore novel therapeutic strategies for HT. Previous studies have shown that luteolin has potent anti-inflammatory effects in vitro and in vivo (38,39) and the mechanisms involved include the activation of NF-κB, which leads to the expression of IL-6 and COX-2 (18,40). Activator protein-1 (AP-1) is also an important transcription factor associated with immune responses.…”

Untitled

“…iNOS Suppresses iNOS expression [33], [35], [34], [43], [81], [82], [84] NO Supresses NO production [33], [35], [48], [34], [43], [56], [81] PGD-2 Inhibits PGD-2 release from human mast cells [51], [52] Leukotrienes Inhibits leukotriene release from human mast cells [51], [52] Leukotriene B4 inhibits LT B4 synthesis [87] Leukotriene C4 No effect [37] Thromboxane B2 Inhibits TX B2 synthesis [87] Histamine Inhibits histamine release from human mast cells [51], [52] GM-CSF Inhibits GM-CSF release from human mast cells [51], [52] TNF-α Suppresses TNF-α expression [48], [34], [36], [42], [53], [55], [56], [81], [93] COX-2 Suppresses COX-2 expression [28], [57], [81], [84] NFκB Inhibits DNA binding and transcription [32], [35], [36], [81], [82] NFκB Does not inhibit NFκB nuclear translocation, DNA binding or phosphorylation but inhibits transcription [85] AP-1 Induces AP-1 DNA binding <...>…”