Study on mechanism of hepatoprotective effect of Chrysanthemum morifolium Ramat. based on metabolomics with network analysis and network pharmacology

被引:4
作者
Yang, Mengxin [1 ]
Sun, Shilin [1 ]
Jia, Xinming [1 ]
Wen, Xuqing [2 ]
Tian, Xi [1 ]
Niu, Yukun [1 ]
Wei, Jinhuan [1 ]
Jin, Yiran [2 ]
Du, Yingfeng [1 ]
机构
[1] Hebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China
[2] Hebei Med Univ, Hosp 2, Shijiazhuang 050000, Hebei, Peoples R China
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2023年 / 1222卷
关键词
Hangju; Acute liver injury; Functional food; Metabolomics; Molecular docking; SERUM; CYTOSCAPE;
D O I
10.1016/j.jchromb.2023.123711
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Hangju (HJ), the dried flower heads of Chrysanthemum morifolium Ramat., has a significant hepatoprotective effect. However, its underlying protection mechanism against acute liver injury (ALI) has been unclear. An in-tegrated strategy based on metabolomics with network analysis and network pharmacology was developed to explore the potential molecular mechanism of HJ on ALI protection. Firstly, differential endogenous metabolites were screened and identified by metabolomics approach and metabolic pathway analysis was performed by MetaboAnalyst. Secondly, marker metabolites were used to construct metabolite-response-enzyme-gene net-works and discover hub metabolites and potential gene targets in network analysis. Thirdly, hub genes through the protein-protein interaction (PPI) network were acquired by the aid of network pharmacology. Finally, the gene targets were taken to intersect with the relevant active ingredients for validation by molecular docking. In total, 48 flavonoids were identified in HJ, which were associated with 8 potential therapeutic targets in network pharmacological analysis. Biochemistry and histopathology analysis demonstrated that HJ exerted hep-atoprotective effects. 28 biomarkers were successfully identified as possible biomarkers for the prevention of ALI. The sphingolipid metabolic pathway and the glycerophospholipid metabolic pathway was considered a crucial signaling pathway by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, phosphatidyl-choline and sphingomyelin were considered as hub metabolites. Twelve enzymes and 38 genes were considered as potential targets in the network analysis. Based on the combined analysis above, HJ was shown to modulate 2 key upstream targets, including PLA2G2A and PLA2G4A. Molecular docking showed that active compounds of HJ had high binding affinity with these key targets. In conclusion, the flavonoid components of HJ can inhibit PLA2 and regulate glycerophospholipid and sphingolipid metabolism pathway to delay the pathological process of ALI, which may be a potential mechanism of HJ against ALI.
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页数:16
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