Chen Lichun, Wang Liziniu, Ao Weizhen, Chen Yu, Li Songjian, Huang Zhiguan, Yu Dan, Dong Yanwen, Gu Jiangyong, Zeng Huiyan
State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
iHuman Institute, School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China.
Biomed Pharmacother. 2022 May;149:112879. doi: 10.1016/j.biopha.2022.112879. Epub 2022 Mar 28.
Ginsenoside Rf, a tetracyclic triterpenoid only present in Panax ginseng, has been proven to relieve lipid metabolism and inflammatory reactions, which can be a potential treatment for nonalcoholic fatty liver disease (NAFLD). Therefore, this study aimed to reveal the underlying mechanisms of ginsenoside Rf in the treatment of early-stage NAFLD (NAFL) by using a bioinformatics method and biological experiments.
Target genes associated with NAFL were screened from the Gene Expression Omnibus (GEO) database, a database repository of high-throughput gene expression data and hybridization arrays, chips, and microarrays. Subsequently, gene set enrichment analysis was performed by using Gene Ontology enrichment analysis tool. Then, the binding capacity between ginsenoside Rf and NAFL-related targets was evaluated by molecular docking. Finally, the FFA-induced HepG2 cell model treated with ginsenoside Rf was adopted to verify the effect of ginsenoside Rf and the related mechanisms.
There were 41 common differentially expressed genes in the GEO dataset. Gene Ontology and Reactome pathway enrichment analysis of the differentially expressed genes showed that many pathways could be related to the pathogenesis of NAFL, including those participating in the cytokine-mediated signaling pathway, G protein-coupled receptor signaling pathway, and response to lipopolysaccharide. Finally, the qRT-PCR analysis results indicated that ginsenoside Rf therapy could ameliorate the transcription of ANXA2, BAZ1A, DNMT3L and MMP9.
Our research discovered the relevant mechanisms and basic pharmacological effects of ginsenoside Rf in the treatment of NAFL. These results might facilitate the development of ginsenoside Rf as an alternative medication for NAFL.
人参皂苷Rf是一种仅存在于人参中的四环三萜类化合物，已被证明可改善脂质代谢和炎症反应，可能是治疗非酒精性脂肪性肝病（NAFLD）的潜在药物。因此，本研究旨在通过生物信息学方法和生物学实验揭示人参皂苷Rf治疗早期非酒精性脂肪性肝病（NAFL）的潜在机制。
从基因表达综合数据库（GEO）中筛选与NAFL相关的靶基因，该数据库是一个高通量基因表达数据以及杂交阵列、芯片和微阵列的数据库存储库。随后，使用基因本体富集分析工具进行基因集富集分析。然后，通过分子对接评估人参皂苷Rf与NAFL相关靶点之间的结合能力。最后，采用人参皂苷Rf处理游离脂肪酸（FFA）诱导的HepG2细胞模型，验证人参皂苷Rf的作用及相关机制。
GEO数据集中有41个共同的差异表达基因。对差异表达基因进行基因本体和Reactome通路富集分析表明，许多通路可能与NAFL的发病机制有关，包括参与细胞因子介导的信号通路、G蛋白偶联受体信号通路以及对脂多糖的反应。最后，qRT-PCR分析结果表明，人参皂苷Rf治疗可改善膜联蛋白A2（ANXA2）、BAZ1A、DNA甲基转移酶3样蛋白（DNMT3L）和基质金属蛋白酶9（MMP9）的转录。
我们的研究发现了人参皂苷Rf治疗NAFL的相关机制和基本药理作用。这些结果可能有助于将人参皂苷Rf开发为NAFL的替代药物。
