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Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice

机译:黄芩苷及其纳米脂质体通过抑制小鼠的TLR4信号传导级联来改善非酒精性脂肪肝疾病

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摘要

As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.
机译:作为天然类黄酮化合物,据报道,黄芩苷(BA)表现出肝保护和抗炎性质。然而,溶解度不良和低生物利用度的特征极大地限制了其应用。此外,BA在非酒精性脂肪肝疾病(NAFLD)中的影响和潜在机制仍然难以捉摸。在本研究中,用黄芩苷或加载的NAFLIN纳米脂质体(Ba-N1)处理蛋氨酸和胆碱缺乏饮食(MCD)诱导的NAFLD小鼠,然后观察到肝细胞病理学变化,生化参数和炎症分子。我们发现MCD组的小鼠显示血浆转氨酶,肝细胞凋亡,肝脂肪积累,肝纤维化和巨噬细胞的浸润和巨噬细胞的显着增加,但与对照组相比,BA和BA-NL显着减弱了MCD - 诱导了上述变化。此外,进一步的分析表明,BA和BA-NL还抑制了COR样受体4(TLR4)信号的上调和MCD小鼠中炎症介质的产生。重要的是,发现BA-NL比小鼠MCD诱导的NAFLD在小鼠上更有效。这些数据表明BA及其纳米脂质体Ba-N1可以有效地保护小鼠免受MCD诱导的NAFLD,其可以通过抑制TLR4信号传导级联介导。

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