Chrysin and its nanoliposome ameliorated non-alcoholic steatohepatitis via inhibiting TLR4 signalling pathway

脂肪性肝炎 TLR4型 肝硬化 纤维化 化学 脂肪肝 肝损伤 白杨素 药理学 炎症 医学 癌症研究 内分泌学 内科学 生物化学 抗氧化剂 疾病 类黄酮
作者
Hao Liu,Ningman Jiang,Ge Kuang,Xia Gong,Jun Hu,Jin Liu,Xinru Yin,Shengwang Wu,Jingyuan Wan
出处
期刊:Journal of Pharmacy and Pharmacology [Oxford University Press]
卷期号:75 (8): 1046-1057
标识
DOI:10.1093/jpp/rgad031
摘要

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease histologically characterized by liver steatosis, hepatocellular injury, inflammation and fibrosis, resulting in cirrhosis and hepatocellular carcinoma, but effective measures and obvious pathogenesis for NASH remain elusive. Chrysin (CH) has been reported to have anti-inflammatory effects but shows lower bioavailability.In this study, a chrysin nanoliposome (CH-NL) was first prepared and characterized. Then, we used the methionine-choline-deficient (MCD) diet to induce a mouse model of NASH. Finally, the effects of CH and CH-NL on NASH were evaluated in the liver of NASH mice.The results showed that CH or CH-NL significantly reduced the accumulation of lipids in hepatocytes, alleviated liver injury, decreased the generation of radical oxygen species, and attenuated the accumulation of collagen fibre in the liver of NASH mice. In addition, CH and its nano-liposomes markedly inhibited the production of inflammatory cytokines and inflammatory cell infiltration in the liver of NASH mice. Further studies found that CH-NL and CH-NL downregulated the MCD diet-induced activation of Toll-like receptor 4 (TLR4) signalling pathway in the liver of mice.CH and its nanoliposome alleviated MCD diet-induced NASH in mice, which might be through inhibiting TLR4 signalling pathway.
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