Increase in insulin sensitivity by the association of chicoric acid and chlorogenic acid contained in a natural chicoric acid extract (NCRAE) of chicory (Cichorium intybus L.) for an antidiabetic effect

J Ethnopharmacol. 2018 Apr 6:215:241-248. doi: 10.1016/j.jep.2017.12.035. Epub 2018 Jan 9.


Ethnopharmacological relevance: Chicory (Cichorium intybus L.) is an indigenous vegetable widely cultivated in Europe, America and Asia. In ancient times, the leaves, flowers, seeds, and roots have been used as a wealth of health benefits including its tonic effects, the ability to ease digestive problems and to detoxify liver. In Indian traditional therapy, chicory was known to possess antidiabetic effect. In the traditional medicine of Bulgaria and Italy, chicory was used as hypoglycemic decoctions.

Aims of the studies: We wanted to obtain the complete chemical composition of the natural chicoric acid extract (NCRAE), a chicory root extract rich in chicoric acid, which previously showed its glucose tolerance effect in normal rats. To investigate if the whole NCRAE is required to be effective, we performed a comparative in vivo experiment on STZ diabetic rats treated either with NCRAE or a mixture composed of the two major compounds of NCRAE.

Materials and methods: LC-MS method has been used to analyze the exhaustive composition of NCRAE: we have determined that chicoric acid and chlorogenic acid represented 83.8% of NCRAE. So, we have prepared a solution mixture of chicoric acid and chlorogenic acid named SCCAM, in order to compare in vivo the antidiabetic effects of this last and NCRAE in streptozotocin diabetic rats. In vitro experiments were performed on L6 cell line both for glucose uptake and for the protective effect against H2O2 oxidative stress. Also, we have evaluated DPPH and ORAC (Oxygen Radical Absorbance Capacity) antioxidative capacities of the two compositions.

Results: The LC-MS analysis confirmed the high abundance of chicoric acid (64.2%) in NCRAE and a second part of NCRAE is composed of caffeoylquinic acids (CQAs) at 19.6% with among them the chlorogenic acid. This result has permitted us to prepare a mixture of synthetic L-chicoric acid (70%) and synthetic chlorogenic acid (30%): the solution is designated SCCAM. Our results showed that both NCRAE and SCCAM are able to improve a glucose tolerance in STZ diabetic rats after a subchronic administration of seven days. Alone NCRAE allows to significantly decrease the basal hyperglycemia after six days of treatment. To explain these difference of effects between NCRAE and SCCAM, we have compared their in vitro effects on the L6 muscle cell line both for the insulin sensitizing effect and for their protective action in pretreatment against H2O2. We have also compared their antioxidant capacities. In conclusion, we demonstrated that NCRAE, a natural extract of chicory (Cichorium intybus) rich in CRA and CQAs improves glucose tolerance and reduces the basal hyperglycemia in STZ diabetic rats.

Keywords: Antidiabetic effect; Chicoric acid and chlorogenic acid; Cichorium intybus L. root extract; L6 cell glucose uptake; L6 cells oxidative stress assay; LC-MS analysis; Streptozotocin diabetic rats.

MeSH terms

  • Animals
  • Antioxidants
  • Caffeic Acids / chemistry
  • Caffeic Acids / pharmacology*
  • Chlorogenic Acid / chemistry
  • Chlorogenic Acid / pharmacology*
  • Cichorium intybus / chemistry*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Hypoglycemic Agents / pharmacology
  • Insulin
  • Insulin Resistance*
  • Medicine, Traditional
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Rats
  • Succinates / chemistry
  • Succinates / pharmacology*


  • Antioxidants
  • Caffeic Acids
  • Hypoglycemic Agents
  • Insulin
  • Plant Extracts
  • Succinates
  • Chlorogenic Acid
  • chicoric acid