TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000558518
  • Gene Name:LDLR
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB17721
  • Drug Name:Astragalus mongholicus root polysaccharides
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:jaundice
  • Tissue:patients tissues

Other information

  • Title:Identification of neolignans with PCSK9 downregulatory and LDLR upregulatory activities from Penthorum chinense and the potential in cholesterol uptake by transcriptional regulation of LDLR via SREBP2
  • Journal:Journal of Ethnopharmacology
  • Published:2021
  • PubMed ID:34111537
  • Abstract:Aim of the study:Based on the traditional use and recent evidences, we investigated the effects of constituents from P. chinense with modulation on proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) expression, and the effect of the most active substance on cholesterol uptake, and genes relevant to lipid metabolism. Materials and methods:The isolation of compounds from the BuOH-soluble extract of 80% methanol extract of P. chinense was conducted using chromatographic methods and the structures were established by interpreting spectroscopic data. Quantitative real time-PCR, and Western blot analysis were performed to monitor the regulatory activity on PCSK9 and LDLR expression. PCSK9-LDLR binding interaction was also tested. The cholesterol uptake in hepatocyte was measured using 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI)-labeled LDL cholesterol. Additionally, gene network analysis of LDLR and responses of its target proteins were carried out to discover genes germane to the effect of active compound on HepG2 cells. Moreover, we performed protein-protein interaction analysis via String and constructed the compound target network using Cytoscape. Results:Two new neolignans and 37 known compounds were characterized from P. chinense. Of the isolated compounds, (7＇E,8S)-2＇,4,8-trihydroxy-3-methoxy-2,4＇-epoxy-8,5＇-neolign-7＇-en-7-one (3), penthorin A (4) and methyl gallate (25) were found to suppress PCSK9 mRNA expression with IC50values of 5.13, 15.56 and 11.66 μM, respectively. However, all the isolated compounds were found to be inactive in PCSK9-LDLR interaction assay. Additionally, a dibenzoxepine-type lignan analog, (7＇E,8S)-2＇,4,8-trihydroxy-3-methoxy-2,4＇-epoxy-8,5＇-neolign-7＇-en-7-one (3) demonstrated to upregulate LDLR mRNA and protein expression via transcriptional factor sterol regulatory element-binding protein 2 (SREBP2). Furthermore, (7＇E,8S)-2＇,4,8-trihydroxy-3-methoxy-2,4＇-epoxy-8,5＇-neolign-7＇-en-7-one (3) increase the LDL-cholesterol uptake in DiI-LDL assay. Conclusion:(7＇E,8S)-2＇,4,8-trihydroxy-3-methoxy-2,4＇-epoxy-8,5＇-neolign-7＇-en-7-one (3) seemed to increase potentially cholesterol uptake via the downregulation of PCSK9 and the activation of LDLR in hepatocytes. Moreover, SREBP2 was found to play an important role in regulation of PCSK9 and LDLR by (7＇E,8S)-2＇,4,8-trihydroxy-3-methoxy-2,4＇-epoxy-8,5＇-neolign-7＇-en-7-one.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3