A transcriptomics and network pharmacology approach to elucidate the mechanism of action of geniposide on carbon tetrachloride-induced liver injury in rats

肝损伤 药理学 转录组 四氯化碳 碱性磷酸酶 信号转导 四氯化碳 作用机理 化学 生物 生物化学 基因表达 基因 有机化学 体外
作者
Chunnan Li,Kaiyue Zhang,Xin Jin,Xiaochen Gao,Jingwei Lv,Jiaming Shen,Xu Gao,Hui Zhang,Jiaming Sun
出处
期刊:International Immunopharmacology [Elsevier BV]
卷期号:120: 110391-110391 被引量:2
标识
DOI:10.1016/j.intimp.2023.110391
摘要

Geniposide, the main active component of Fructus Gardeniae (FG), is known to confer protection against liver diseases. Herein we explored the hepatoprotective effects of geniposide and elucidated its molecular mechanism by transcriptome RNA-seq and network pharmacology. Liver injury was modeled by intraperitoneally injecting CCl4 (0.15% prepared with refined peanut oil) at a dose of 1.5 mL/kg thrice a week; from the second week, rats were administered geniposide (20 mg/kg or 40 mg/kg) by gavage for 6 weeks. Serum and liver samples were then collected to assess liver function indicators and inflammatory factors and to observe pathological changes in the liver. The Illumina HiSeq 4000 platform was used to obtain transcriptome data from the liver tissue of rats after geniposide administration. Core targets and pathways related to the liver protection mechanism of geniposide were further analyzed by integrating transcriptomics and network pharmacology. Differentially expressed genes (DEGs), core targets, and signaling pathways were identified by methods such as q-PCR, molecular docking, and Western blotting. We found that after geniposide administration, the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and inflammatory factors decreased in the model group, and liver injury cells be effectively repaired. RNA-seq data analysis showed that compared to control group, the model group reversed 1,451 DEGs; further, compared to model group, geniposide reversed 511 DEGs. Eight key targets, including PIK3R1, ACOX3, and EGF, were found through further analyses. Geniposide was determined to mainly regulate the PPAR signaling pathway, apoptosis signaling pathway, and MAPK signaling pathway in liver tissues. To summarize, the protective and restorative effects of geniposide on rat liver may seem to be related to its efficacy in inhibiting the activation of inflammatory pathways, thereby reducing cell apoptosis. Our findings should serve as the basis for the development of functional foods or drugs to prevent and treat liver diseases.
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