Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
2 Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China.
J Tradit Chin Med. 2023 Oct;43(6):1092-1102. doi: 10.19852/j.cnki.jtcm.2023.06.004.
To evaluate the effects of Sanren Tang (SRT, ) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice and to investigate the hepatic transcriptome regulated by SRT.
The primary SRT components were identified using ultra-high-performance liquid chromatography-high-resolution accurate mass spectrometry. The SRT-induced pharmacological effects on HFD-induced NAFLD were evaluated in mice for 16 weeks. Obeticholic acid was used as a control drug. Body weight, food intake, and homeostatic model assessment for insulin resistance (HOMA-IR) index were analysed. Hepatic histological changes were observed in haematoxylin and eosin-stained sections and quantified using the NAFLD activity score (NAS). Serum alanine aminotransferase (ALT) and hepatic triglyceride (TG) levels were measured. Lipids in hepatocytes were visualised by Oil red staining. RNA-sequencing was performed to determine the transcriptome profile of the liver tissue. The differentially expressed genes were validated using real-time polymerase chain reaction and Western blotting.
Four principal compounds were identified in the SRT: adenosine, amygdalin, luteoloside, and magnolol. SRT ameliorated hepatic histology and lipid deposition in the NAFLD mice, and decreased HOMA-IR, NAS and ALT, and hepatic TG levels. Hepatic transcriptome analysis revealed 232 HFD-regulated genes that were reversed by SRT simultaneously. Retinol metabolism, cytokine-cytokine receptor interaction, and peroxisome proliferator-activated receptor (PPAR) γ signalling were the top three SRT-regulated pathways in NAFLD.
SRT significantly ameliorated HFD-induced NAFLD, which was correlated with the regulation of genes enriched in the retinol metabolism, cytokine-cytokine receptor interaction, and PPARγ signalling pathways.
评价三仁汤（SRT）对高脂饮食（HFD）诱导的非酒精性脂肪性肝病（NAFLD）的影响，并探讨 SRT 调节的肝转录组。
采用超高效液相色谱-高分辨精确质量质谱法鉴定 SRT 的主要成分。在 16 周的时间里，用 SRT 处理 HFD 诱导的 NAFLD 小鼠，评估 SRT 的药理作用。熊去氧胆酸（UDCA）被用作对照药物。分析体重、摄食量和稳态模型评估的胰岛素抵抗指数（HOMA-IR）。苏木精和伊红（H&E）染色切片观察肝组织学变化，并采用 NAFLD 活动评分（NAS）进行量化。检测血清丙氨酸转氨酶（ALT）和肝甘油三酯（TG）水平。油红染色观察肝细胞内脂质。采用 RNA 测序（RNA-seq）确定肝组织的转录组谱。使用实时聚合酶链反应（PCR）和 Western 印迹验证差异表达基因。
SRT 中鉴定出 4 种主要化合物：腺苷、苦杏仁苷、芦丁和厚朴酚。SRT 改善了 NAFLD 小鼠的肝组织学和脂质沉积，并降低了 HOMA-IR、NAS 和 ALT 以及肝 TG 水平。肝转录组分析显示，232 个 HFD 调节的基因被 SRT 同时逆转。视黄醇代谢、细胞因子-细胞因子受体相互作用和过氧化物酶体增殖物激活受体（PPAR）γ信号通路是 SRT 调节 NAFLD 的前三大通路。
SRT 显著改善了 HFD 诱导的 NAFLD，这与视黄醇代谢、细胞因子-细胞因子受体相互作用和 PPARγ信号通路中富集的基因的调节有关。
