4). In the necroinflammatory finding of the liver, two mice showed hepatitis in the alcohol group, whereas no inflammation was observed in the KRG, urushiol, and probiotics groups. LPS-induced Kupffer SB431542 research buy cell activation is most likely the primary pathogenesis of ALD. LPS

binds to the LPS-binding protein, and is initially transferred to CD 14 and eventually to TLR-4 and myeloid differentiation factor-2 complexes in Kupffer cells. The activation of TLR-4, which is a transmembrane protein that responds primarily to LPS, activates innate immune responses that involve various transcription factors and proinflammatory cytokines [4], [5] and [17]. TLR-4-deficient mice had lower levels of steatosis, inflammation, and proinflammatory cytokines [17] and [18]. Another study showed that chronic alcohol exposure leads to the hyporesponsiveness of monocytes to LPS because of decreased negative regulators of TLR-4 activation [19]. RAD001 order The present study showed that KRG and probiotic diets did not improve

liver function. However, these diets effectively reduced alcohol-induced TLR-4 expression of the liver tissue. These results match those of a previous study demonstrating that the hepatic TLR-4 overexpression that had been increased in LPS- and D-galactosamine-fed rats was significantly downregulated by a Lactobacillus casei Zhang treatment [20]. Another report suggested that ginsenoside Re suppresses the expression of proinflammatory cytokines and the activation of their transcription factor NF-κB by inhibiting the binding of LPS to TLR-4 on immune cells such as macrophages [12]. Together, these results suggest that probiotic Urocanase and KRG diets display anti-ALD effects by suppressing TLR-4 expression. TLR-4 levels of the liver tissue were also decreased in urushiol-fed mice compared with those in alcohol-fed mice.

According to a study that evaluated the biological effects of urushiol, the antibacterial effect against Helicobacter pylori and anti-inflammatory effect due to the reduction of the IL-1β levels in gastric tissue were demonstrated using a mouse model [15]. The current study is the first to statistically evaluate the effects of urushiol on TLR-4 levels of the liver tissue using an ALD mouse model. In addition to its antibacterial and anti-inflammatory effects on the stomach (as demonstrated by earlier studies), we hypothesize that urushiol also exerts anti-ALD effects by modulating cytokines. This study also demonstrated that the TNF-α level in the liver tissue of the KRG group was significantly lower than those in the alcohol group. Previous data showed that Panax notoginseng saponins reduced significantly the TNF-α level in CCl4-treated mice with hepatic fibrosis [21]. Another study demonstrated that ginsenoside Rg1 inhibited LPS-induced TNF-α production via dendritic cells [22]. KRG saponin fraction inhibited nitric oxide production and attenuated the release of TNF-α, IL-6, and granulocyte–monocyte colony-stimulating factor [23].