The Effect of Phloroglucinol, A Component of Ecklonia cava Extract, on Hepatic Glucose Production

Mar Drugs. 2017 Apr 5;15(4):106. doi: 10.3390/md15040106.


Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes. The expression of phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase mRNA and protein (G6Pase), enzymes involved in gluconeogenesis, were inhibited in liver tissue from phloroglucinol-treated mice and in phloroglucinol-treated HepG2 cells. In addition, phloroglucinol treatment increased phosphorylated AMP-activated protein kinase (AMPK)α in HepG2 cells. Treatment with compound C, an AMPKα inhibitor, inhibited the increase of phosphorylated AMPKα and the decrease of PEPCK and G6Pase expression caused by phloroglucinol treatment. We conclude that phloroglucinol may inhibit hepatic gluconeogenesis via modulating the AMPKα signaling pathway, and thus lower blood glucose levels.

Keywords: AMPKα; G6Pase; PEPCK; Phloroglucinol; gluconeogenesis.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet, High-Fat
  • Gluconeogenesis / drug effects*
  • Glucose / metabolism*
  • Glucose-6-Phosphatase / metabolism
  • Hep G2 Cells
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phaeophyta / chemistry*
  • Phloroglucinol / pharmacology*
  • Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects


  • Blood Glucose
  • Hypoglycemic Agents
  • Phloroglucinol
  • AMP-Activated Protein Kinases
  • Glucose-6-Phosphatase
  • Phosphoenolpyruvate Carboxykinase (ATP)
  • Glucose