title: Antihyperglycemic effect of a natural chicoric acid extract of chicory (Cichorium intybus L.): a comparative in vitro study with the effects of caffeic and ferulic acids.
abstract: BACKGROUND
  In Eurasia folk medicine, roots of chicory (Cichorium intybus L.) have been reported to exert antidiabetic benefits. In vitro, a natural chicoric acid extract (NCRAE) from Cichorium intybus root has been shown to increase insulin secretion by pancreatic β-cells and glucose uptake by muscle cells.
  
  
  METHODS
  In vitro experiments were designed to compare the effects of two hydroxycinnamic acids, caffeic and ferulic acids, to those obtained with NCRAE (50 and 100 µg.mL(-1)) on the three major tissues implicated in glycemic regulation (pancreas, muscle and liver). In vivo experiments were performed in Wistar rats submitted to a daily intraperitoneal injection of NCRAE (3, 15 or 30 mg kg(-1)) for 4 days. On the fourth day, an intraperitoneal glucose tolerance test (IPGTT; 1 g kg(-1)) was carried out.
  
  
  RESULTS
  Our results show that the three compounds we used are able each to induce an original response. Caffeic acid mainly promotes a decrease in hepatic glycogenolysis. Ferulic acid elicits a clear increase of insulin release and a reduction of hepatic glycogenolysis. However, this compound induces an inhibition of muscle glucose uptake. NCRAE provokes an increase of insulin release and glucose uptake without any effect on hepatic glycogenolysis. We could also show that none of these compounds implicates hepatic glucose 6-phosphatase in contrast to chlorogenic acid, known as an inhibitor of glucose 6-phosphatase and which is able to decrease glucose output from hepatocytes. Our results point out that NCRAE is able to decrease blood glucose without any effect hepatic effect. Our in vivo experiments bring evidence that 4 daily IP administrations of NCRAE improve IP glucose tolerance in a dose-dependent manner and mainly via an insulin sensitizing effect.
  
  
  CONCLUSIONS
  We conclude that NCRAE presents an antihyperglycemic effect essentially due to a peripheral effect on muscle glucose uptake.
authors.affiliation: Université Montpellier I, 4 Boulevard Henri IV, 34093 Montpellier cedex 5, France; CNRS FRE 3400, Centre de Pharmacologie et Innovation dans le Diabète, UFR des Sciences Pharmaceutiques et Biologiques, 15 Avenue Charles Flahault, BP14491, 34093 Montpellier cedex 5, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Azay-Milhau
authors.forename: Karine
authors.initials: K
authors.lastname: Ferrare
authors.forename: Jeremy
authors.initials: J
authors.lastname: Leroy
authors.forename: Jordan
authors.initials: J
authors.lastname: Aubaterre
authors.forename: Michel
authors.initials: M
authors.lastname: Tournier
authors.forename: Anne-Dominique
authors.initials: AD
authors.lastname: Lajoix
authors.forename: Didier
authors.initials: D
authors.lastname: Tousch
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018651:Cichorium intybus; D003373:Coumaric Acids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009132:Muscles / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates
chemical_list: D002109:Caffeic Acids; D003373:Coumaric Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D013386:Succinates; D006003:Glycogen; C004999:ferulic acid; D005952:Glucose-6-Phosphatase; D005947:Glucose; C100435:chicoric acid; C040048:caffeic acid
keywords: Antihyperglycemic effect; Chicoric acid extract; Glucose 6-phosphatase; Glucose tolerance test; Hydroxycinnamic acids; In vitro experiments