title: Structural constraints and importance of caffeic acid moiety for anti-hyperglycemic effects of caffeoylquinic acids from chicory.
abstract: Chicory (Cichorium intybus L.) is a perennial herb often consumed as a vegetable, whereas the ground and roasted roots are blended as a coffee substitute. Caffeoylquinic or chlorogenic acids (CQA), the abundant intermediates of lignin biosynthesis in chicory, have been reported to improve glucose metabolism in humans, but the functional group in their structure responsible for this effect has not been yet characterized.
  
  
  
  Here, we showed that three di-O-caffeoylquinic acids suppressed hepatic glucose production in H4IIE rat hepatoma cells by reducing expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes that regulate hepatic gluconeogenesis. Direct comparisons between CQAs and their metabolites (3-caffeoylquinic, caffeic, and quinic acids) revealed the caffeic acid moiety alone was responsible for the observed effects. Further analysis suggested the activation of PI3K and MAPK pathways as a method of controlling gene expression was shared between caffeoylquinic and caffeic acids. These compounds promoted increased mitochondrial respiration and cellular metabolism, in part by inducing oxidative phosphorylation and proton leak.
  
  
  
  We concluded that the caffeic acid moiety was important for suppression of hepatic gluconeogenesis and hyperglycemia, ultimately strengthening the link between dietary interventions based on caffeic acid-containing plant foods and healthy glucose metabolism.
authors.affiliation: Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, USA.|Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, Raleigh, NC, USA.
authors.forename: Kimberly M Palatini
authors.initials: KMP
authors.lastname: Jackson
authors.affiliation: Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, USA.|Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.
authors.forename: Thirumurugan
authors.initials: T
authors.lastname: Rathinasabapathy
authors.affiliation: Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, USA.|Department of Animal Science, North Carolina State University, Raleigh, NC, USA.
authors.forename: Debora
authors.initials: D
authors.lastname: Esposito
authors.affiliation: Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, USA.|Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, Raleigh, NC, USA.
authors.forename: Slavko
authors.initials: S
authors.lastname: Komarnytsky
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018651:Cichorium intybus / Q000737:chemistry*; D005943:Gluconeogenesis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D010597:Pharmacogenetics; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D018517:Plant Roots / Q000737:chemistry; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D007004:Hypoglycemic Agents; C472707:caffeoylquinic acid; D011801:Quinic Acid; D019869:Phosphatidylinositol 3-Kinases
keywords: Blood glucose; Cell bioenergetics; Diabetes; Dietary supplementation; Metabolic syndrome