Liu Lu, Sun Sen, Li Xiaohua
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China.
Department of Anesthesiology, Shanghai Pulmonary Hospital, Shanghai, 200433, China.
Mol Cell Probes. 2023 Oct;71:101926. doi: 10.1016/j.mcp.2023.101926. Epub 2023 Aug 22.
Non-alcohol fatty liver disease (NAFLD) is the most prevalent hepatopathy in China, with few effective cures currently. This work aimed to confirm the effect of DHM in vivo/vitro and explore the potential mechanism based on a network pharmacology-based approach.
The rats were fed using a high-fat diet (HFD) to accumulate lipid. DHM at different concentrations was used to treat the HFD rats. The serum total cholesterol (TC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected using ELISA kits. The target genes of DHM against NAFLD were screened by online databases. Then, the cytotoxicity of DHM in primary hepatocytes and HepG2 cells was determined by MTT reagent. qRT-PCR was used to quantify the expression level of PPAGR and CASP3 mRNA. Cell apoptosis and intracellular triglyceride (TG) were detected.
HFD diet increased rat liver weight/body weight ratio, serum TC, ALT, and AST. But DHM treatment can reduce these elevated indicators. DHM targeted 14 potential genes in NAFLD. PPARG and CASP3 were two hub genes for DHM against NAFLD, with score factor coefficients of -7.1 and -6.8 kcal/mol. DHM reduced the increased PPARG mRNA level and intracellular TG induced by palmitic acid. DHM can reduce the increased CASP3 mRNA level and cell apoptosis induced by palmitic acid.
This work demonstrates a mechanism of DHM that alleviates lipid metabolism disorder and cell apoptosis for the treatment of NAFLD, evidencing the potential application of DHM in NAFLD.
非酒精性脂肪性肝病（NAFLD）是中国最常见的肝病，目前有效治疗方法较少。本研究旨在通过基于网络药理学的方法，在体内/体外证实二氢杨梅素（DHM）的作用，并探索其潜在机制。
采用高脂饮食（HFD）喂养大鼠以积累脂质。用不同浓度的DHM处理HFD大鼠。使用酶联免疫吸附测定（ELISA）试剂盒检测血清总胆固醇（TC）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。通过在线数据库筛选DHM抗NAFLD的靶基因。然后，用MTT试剂测定DHM对原代肝细胞和HepG2细胞的细胞毒性。采用qRT-PCR定量PPAGR和CASP3 mRNA的表达水平。检测细胞凋亡和细胞内甘油三酯（TG）。
HFD饮食增加了大鼠肝脏重量/体重比、血清TC、ALT和AST。但DHM处理可降低这些升高的指标。DHM在NAFLD中靶向14个潜在基因。PPARG和CASP3是DHM抗NAFLD的两个关键基因，得分因子系数分别为-7.1和-6.8 kcal/mol。DHM降低了棕榈酸诱导的PPARG mRNA水平升高和细胞内TG。DHM可降低棕榈酸诱导的CASP3 mRNA水平升高和细胞凋亡。
本研究揭示了DHM通过减轻脂质代谢紊乱和细胞凋亡来治疗NAFLD的机制，证明了DHM在NAFLD中的潜在应用价值。
