To study the quality markers of Danhe granule for treatment of hyperlipidemia,the network of “hyperlipidemia-common target-components of Danhe granules in vivo” was constructed by Cytoscape software based on the results of in vivo component analysis.To determine the key target and component,the biological process,pathway enrichment and network topology of the common target were analyzed by DAVID and String database,respectively.Then HepG2 cells induced by oleic acid(OA) were selected to establish a lipid accumulation cell model to verify the lipid-lowering efficacy of the key components.Finally,combined with the content,stability and characteristics of the related components in the preparation,the quality markers were determined.Result showed that components of Danhe granule in vivo act on 10 disease targets of hyperlipidemia,including CES1,ADORA2A,ADORA1,APOB,LDLR,PPARA,PPARG,INSR,ESR2 and ESR1,which mainly regulated the process of lipid metabolism and the signal pathways of PPAR and cAMP.It was found that LDLR,PPARA and PPARG may be the key targets for the lipid-lowering effect of Danhe granules,while the components interacted with the key targets were resveratrol and naringenin.Futhermore,resveratrol or naringenin could not only reduce the number of intracellular lipid droplets,improve the severity of lipid accumulation in HepG2 cells,but also significantly reduce the content of intracellular triglyceride which may be the key components.Considering that the resveratrol and naringenin in vivo come from polydatin and naringin in preparation,while polydatin and naringin are rich and stable in preparation with obvious characteristics,they thus could be used as the quality markers of Danhe granules in the treatment of hyperlipidemia.This study provides a reasonable candidate quality control index for the establishment of the quality standard of Danhe granules.
关键词
丹荷颗粒质量标志物质量控制指标网络药理学高脂血症
Keywords
Danhe granulesquality markerquality control indexnetwork pharmacologyhyperlipidemia
Study on Discovery of Quality Markers for Treatment of Hyperlipidemia with Danhe Granules
Research Progress on Selection Methods for Quality Markers in Famous Classical Formulas and Related Thoughts
Liver Untargeted Metabolomics of Hyperlipidemic Hamsters Based on Liquid Chromatography-Time-of-flight Mass Spectrometry
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College of Pharmaceutical Engineering of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine
State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine
Shanghai Zhen Ren Tang Pharmaceutical Co.,Ltd
Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Chinese Materia Medica
Tianjin University of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine