Ethnopharmacological relevance

Cholestasis caused by bile secretion and excretion disorders is a serious manifestation of liver disease. With limited treatment methods, it affects millions of people worldwide. Huangqi decoction (HQD), an effective traditional Chinese medicine, is used to treat chronic cholestatic liver diseases. However, the action mechanisms of it were not fully elucidated.

Aim of the study

We aim to investigate the therapeutic effect of HQD, and its active component, astragalosides, against α-naphthylisothiocyanate (ANIT)-induced cholestasis in rats based on targeted metabolomics analysis and revel the potential mechanism.

Materials and methods

The therapeutic effect of HQD and astragalosides on ANIT-induced cholestasis model rats were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The levels of bile acids (BAs) and free fatty acids (FFAs) in serum and liver tissues were measured by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQMS). qRT-PCR and Western blot analysis were used to measure the expression of nuclear hormone receptor, membrane receptor and BA transporter protein in cholestatic rats before and after HQD and astragalosides treatment.

Results

The obtained data showed that the administration of ANIT caused obvious cholestasis with significantly increased intrahepatic retention of hydrophobic BAs and altered FFAs, which were consistent with the liver histopathological and serum biochemical findings. HQD and astragalosides treatment were able to attenuate ANIT-induced BAs and FFAs perturbation, ameliorate the impaired liver function, histopathological ductular reaction, and lipid peroxidation damage by ANIT. Elevated mRNA and protein expression of transporters related to BA metabolism and genes related to lipogenesis and lipid oxidation metabolism in cholestasis were attenuated or normalized by HQD and astragalosides treatment.

Conclusions

Intervention by ANIT can significantly change the homeostasis of BAs and FFAs. HQD and astragalosides exerted a hepatoprotective effect against cholestatic liver injury by restoring the altered BA and FFA metabolism through the improvement of BA transporter, nucleus hormone receptor, and membrane receptor.

中文翻译：

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代谢组学分析描述了黄芪汤和黄芪总苷对α-萘基异硫氰酸酯（ANIT）诱导的胆汁淤积的治疗作用

民族药理学意义

由胆汁分泌和排泄障碍引起的胆汁淤积是肝病的严重表现。由于治疗方法有限，它影响了全世界数百万人。黄芪汤（HQD）是一种有效的中药，用于治疗慢性胆汁淤积性肝病。但是，其作用机理尚未完全阐明。

研究目的

我们旨在根据靶向代谢组学分析研究HQD及其活性成分黄芪总苷对α-萘基异硫氰酸酯（ANIT）诱导的胆汁淤积的治疗作用，并揭示其潜在机制。

材料和方法

通过血清生化分析评估了HQD和黄芪总苷对ANIT诱导的胆汁淤积模型大鼠的治疗作用。通过组织病理学鉴定肝损害。通过超高效液相色谱-三重四极杆质谱（UPLC-TQMS）测量血清和肝组织中的胆汁酸（BAs）和游离脂肪酸（FFA）含量。采用qRT-PCR和Western blot分析检测HQD和黄芪甲苷处理前后胆汁淤积大鼠核激素受体，膜受体和BA转运蛋白的表达。

结果

获得的数据表明，ANIT的使用引起明显的胆汁淤积，肝内疏水性BAs的保留显着增加，FFA改变，这与肝脏组织病理学和血清生化结果一致。HQD和黄芪甲苷处理能够减轻ANIT诱导的BAs和FFAs摄动，减轻肝功能受损，组织病理学导管反应和ANIT引起的脂质过氧化损伤。HQD和黄芪总皂苷处理可减轻或归化胆汁淤积症中与BA代谢有关的转运蛋白和与脂质生成和脂质氧化代谢有关的基因的mRNA和蛋白质表达。

结论

ANIT的干预可以显着改变BA和FFA的体内平衡。HQD和黄芪总苷通过改善BA转运蛋白，细胞核激素受体和膜受体来恢复改变的BA和FFA代谢，从而对胆汁淤积性肝损伤具有保肝作用。