title: Arctigenin antagonizes mineralocorticoid receptor to inhibit the transcription of Na/K-ATPase.
abstract: BACKGROUND
  Hypertension is one of the most important risk factors in cardiovascular disease and is the most common chronic disease. Mineralocorticoid receptor (MR) antagonists have been successfully used in clinic for the treatment of hypertension.
  
  
  OBJECTIVE
  Our study aims to investigate whether Arctigenin can antagonize MR and inhibit the transcription of Na/K-ATPase.
  
  
  METHODS
  The yeast two-hybrid assay was used to screen natural products and Arctigenin was identified as an MR antagonist. The direct binding of Arctigenin to MR was determined using assays based on surface plasmon resonance, differential scanning calorimetry and fluorescence quenching. Furthermore, results from mammalian one-hybrid and transcriptional activation experiments also confirmed that Arctigenin can potently antagonize MR in cells. We demonstrated that Arctigenin can decrease the level of Na/K-ATPase mRNA by antagonizing MR in HK-2 cells.
  
  
  RESULTS
  Our findings show that Arctigenin can effectively decrease Na/K-ATPase transcription; thus highlight its potential as an anti-hypertensive drug lead compound.
  
  
  CONCLUSIONS
  Our current findings demonstrate that Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression. Our work provides a hint for the drug discovery against cardiovascular disease.
authors.affiliation: a Department of Cardiology , Xiamen Heart Center , Xiamen , P.R. China and.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: b The Second Hospital of Xiamen , Xiamen , P.R. China.
authors.forename: Meili
authors.initials: M
authors.lastname: Zhou
authors.affiliation: a Department of Cardiology , Xiamen Heart Center , Xiamen , P.R. China and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D005663:Furans / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017705:Lignans / Q000008:administration & dosage*; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics*; D020349:Surface Plasmon Resonance; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D005663:Furans; D017705:Lignans; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000254:Sodium-Potassium-Exchanging ATPase; C071942:arctigenin
keywords: Arctigenin; Na/K-ATPase; hypertension; mineralocorticoid receptor