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白杨素及其纳米脂质体通过抑制 TLR4 信号通路改善非酒精性脂肪性肝炎。

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

机构信息

Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Chongqing Medical University, Chongqing, China.

Department of Anatomy, Chongqing Medical University, Chongqing, China.

出版信息

J Pharm Pharmacol. 2023 Aug 1;75(8):1046-1057. doi: 10.1093/jpp/rgad031.

Abstract

OBJECTIVES

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.

METHODS

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.

KEY FINDINGS

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.

CONCLUSIONS

CH and its nanoliposome alleviated MCD diet-induced NASH in mice, which might be through inhibiting TLR4 signalling pathway.

摘要

目的

非酒精性脂肪性肝炎(NASH)是一种慢性肝脏疾病,其组织学特征为肝脂肪变性、肝细胞损伤、炎症和纤维化,导致肝硬化和肝细胞癌,但 NASH 仍缺乏有效措施和明显的发病机制。白杨素(CH)具有抗炎作用,但生物利用度较低。

方法

本研究首次制备和表征了白杨素纳米脂质体(CH-NL)。然后,我们使用蛋氨酸-胆碱缺乏(MCD)饮食诱导 NASH 小鼠模型。最后,在 NASH 小鼠的肝脏中评估 CH 和 CH-NL 对 NASH 的影响。

主要发现

结果表明,CH 或 CH-NL 可显著减少肝细胞内脂质堆积,减轻肝损伤,减少活性氧的生成,并减轻 NASH 小鼠肝脏胶原纤维的堆积。此外,CH 和其纳米脂质体明显抑制了 NASH 小鼠肝脏中炎症细胞因子的产生和炎症细胞浸润。进一步的研究发现,CH-NL 和 CH-NL 下调了 MCD 饮食诱导的小鼠肝脏中 Toll 样受体 4(TLR4)信号通路的激活。

结论

CH 及其纳米脂质体减轻了 MCD 饮食诱导的 NASH 小鼠模型,这可能是通过抑制 TLR4 信号通路。

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