Honokiol Improves Insulin Resistance, Hepatic Steatosis, and Inflammation in Type 2 Diabetic db/ db Mice

Int J Mol Sci. 2019 May 9;20(9):2303. doi: 10.3390/ijms20092303.


This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Male C57BL/KsJ-db/db mice were fed a normal diet with or without HON (0.02%, w/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.

Keywords: anti-inflammatory effect; anti-insulin resistance effect; anti-steatotic effect; honokiol; type 2 diabetic db/db mice.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / pathology
  • Animals
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Dyslipidemias / blood
  • Dyslipidemias / complications
  • Fatty Liver / blood
  • Fatty Liver / complications
  • Fatty Liver / drug therapy*
  • Fatty Liver / pathology
  • Feeding Behavior / drug effects
  • Homeostasis / drug effects
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Insulin Resistance*
  • Leptin / blood
  • Lignans / pharmacology
  • Lignans / therapeutic use*
  • Lipids / blood
  • Male
  • Mice, Inbred C57BL
  • Organ Size / drug effects


  • Biphenyl Compounds
  • Blood Glucose
  • Cytokines
  • Inflammation Mediators
  • Leptin
  • Lignans
  • Lipids
  • honokiol