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茵陈蒿汤通过增加NR1H4和APOA1的表达来缓解高脂饮食诱导的非酒精性脂肪性肝病。

Yinchenhao Tang alleviates high fat diet induced NAFLD by increasing NR1H4 and APOA1 expression.

作者信息

Xu Li, Cui Hongliang

机构信息

Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.

出版信息

J Tradit Complement Med. 2023 Feb 24;13(4):325-336. doi: 10.1016/j.jtcme.2023.02.010. eCollection 2023 Jul.

Abstract

BACKGROUND AND AIM

Traditional Chinese medicine Yinchenhao Tang (YCHT) demonstrated benefits when treating nonalcoholic fatty liver disease (NAFLD), but the dose effects and potential targets are still ambiguous. In this study, different concentrations of YCHT were employed to treat NAFLD and the underlying therapeutic targets were investigated.

EXPERIMENTAL PROCEDURE

Kunming mice were fed with high fat diet (HFD) for 8 weeks to induce NAFLD, then treated with 3 different concentrations of YCHT. Hepatic pathological changes and serum lipid levels were examined. Network pharmacology was applied to screen the potential targets of YCHT for NAFLD modulation. NR1H4 and APOA1 expression was evaluated by QPCR and western blotting. Immunohistochemistry (IHC) staining was conducted to visualize the localization pattern of NR1H4 and APOA1 in the liver.

RESULTS

YCHT significantly reduced liver lipid storage and improved the liver pathological status of NAFLD mice. The serum lipid levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, were remarkably reduced by the middle and high dose YCHT. There are 35 potential targets for YCHT to regulate NAFLD. HFD suppressed both RNA and protein expression of NR1H4 and APOA1, while YCHT elevated NR1H4 and APOA1 expression. IHC staining indicated that NR1H4 was mainly located in the cell nucleus and the APOA1 signal was observed at the liver sinusoid or cytoplasm.

CONCLUSION

YCHT can effectively ameliorate HFD induced NAFLD by modulating the promising targets of NR1H4 and APOA1.

摘要

背景与目的

中药茵陈蒿汤(YCHT)在治疗非酒精性脂肪性肝病(NAFLD)时显示出益处,但其剂量效应和潜在靶点仍不明确。在本研究中,采用不同浓度的茵陈蒿汤治疗NAFLD,并研究其潜在的治疗靶点。

实验方法

将昆明小鼠用高脂饮食(HFD)喂养8周以诱导NAFLD,然后用3种不同浓度的茵陈蒿汤进行治疗。检测肝脏病理变化和血脂水平。应用网络药理学筛选茵陈蒿汤调节NAFLD的潜在靶点。通过QPCR和蛋白质免疫印迹法评估NR1H4和APOA1的表达。进行免疫组织化学(IHC)染色以观察NR1H4和APOA1在肝脏中的定位模式。

结果

茵陈蒿汤显著减少肝脏脂质蓄积,改善NAFLD小鼠的肝脏病理状态。中、高剂量茵陈蒿汤显著降低血脂水平以及丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平。茵陈蒿汤调节NAFLD有35个潜在靶点。高脂饮食抑制NR1H4和APOA1的RNA和蛋白质表达,而茵陈蒿汤提高NR1H4和APOA1的表达。免疫组织化学染色表明,NR1H4主要位于细胞核,在肝血窦或细胞质中观察到APOA1信号。

结论

茵陈蒿汤可通过调节有前景的靶点NR1H4和APOA1有效改善高脂饮食诱导的NAFLD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c168/10310876/75fd5c1e128b/ga1.jpg

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