title: A gut microbial metabolite of ginsenosides, compound K, induces intestinal glucose absorption and Na(+) /glucose cotransporter 1 gene expression through activation of cAMP response element binding protein.
abstract: METHODS
  The Na(+) /glucose cotransporter 1 (SGLT1) plays a crucial role in glucose uptake in intestinal epithelial cells (IECs), which has been shown essential in ameliorating intestinal inflammation. Ginseng has historically been used to treat inflammatory disorders. Understanding the regulatory mechanism of ginseng-mediated induction of SGLT1 gene expression in human intestinal cells is therefore important.
  
  
  RESULTS
  We demonstrate that ginsenoside compound K (CK) enhances SGLT1-mediated glucose uptake in mice and human intestinal Caco-2 cells. Transient transfection analysis using SGLT1 promoter-luciferase reporters demonstrated that the presence of an essential cAMP response element (CRE) is required for CK-mediated induction of SGLT1 gene expression. The ChIP assays indicated that increased CRE-binding protein (CREB) and CREB-binding protein (CBP) binding to the SGLT1 promoter in CK-treated cells is associated with an activated chromatin state. Our result showed that the increased CREB phosphorylation is directly correlated with SGLT1 expression in IECs. Further studies indicated that the epidermal growth factor receptor (EGFR) signaling pathway is involved in the CK-mediated effect.
  
  
  CONCLUSIONS
  These findings provide a novel mechanism for the CK-mediated upregulation of SGLT1 expression through EGFR-CREB signaling activation, which could contribute to reducing gut inflammation.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Wang
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Huang
authors.forename: Fang-Na
authors.initials: FN
authors.lastname: Chan
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Su
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Kuo
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Huang
authors.forename: Mei-Whey
authors.initials: MW
authors.lastname: Hung
authors.forename: Hang-Chin
authors.initials: HC
authors.lastname: Lin
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Chang
authors.forename: Tsu-Chung
authors.initials: TC
authors.lastname: Chang
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D047369:Chromatin Immunoprecipitation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D015870:Gene Expression; D036145:Ginsenosides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein; D036145:Ginsenosides; D005947:Glucose; D051269:Sodium-Glucose Transporter 1; C495674:SLC5A1 protein, human; C112772:ginsenoside compound K; C494363:CREBBP protein, human
keywords: Caco-2 cells; Na+/glucose cotransporter 1 promoter; Natural products; cAMP response element