机构地区:[1]Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006,China [2]Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Taiyuan 030006,China [3]Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province,Taiyuan 030006,China
出 处:《Chinese Journal of Natural Medicines》2023年第3期197-213,共17页中国天然药物(英文版)
基 金:the National Nature Science Foundation of China(No.82004502);the Youth Science and Technology Research Fund of Shanxi Province(No.201901D211138);the National S&T Major Projects for“Major New Drugs Innovation and Development”(No.2017ZX09301047);the Key R&D Project of Shanxi Province(No.202102130501010).
摘 要:Angelicae Sinensis Radix(AS)is reproted to exert anti-depression effect(ADE)and nourishing blood effect(NBE)in a rat model of depression.The correlation between the two therapeutic effects and its underlying mechanisms deserves further study.The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics,network pharmacology and molecular docking.According to metabolomics analysis,30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression.Furthermore,principal component analysis and correlation analysis showed that glutathione,sphinganine,and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators,indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS.Then,a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis,where a total of 107 pathways were collected.Moreover,37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer(UPLC-Triple-TOF/MS)in AS extract that passed the filtering criteria were used for network pharmacology,where 46 targets were associated with the ADE and NBE of AS.Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS.Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins(PIK3CA and PIK3CD)in sphingolipid metabolism.Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism.Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.
关 键 词:Angelicae Sinensis Radix Blood deficiency syndrome Depression METABONOMICS Network pharmacology Sphingolipid metabolism
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