Licorice extract ameliorates hyperglycemia through reshaping gut microbiota structure and inhibiting TLR4/NF-κB signaling pathway in type 2 diabetic mice

Food Res Int. 2022 Mar:153:110945. doi: 10.1016/j.foodres.2022.110945. Epub 2022 Jan 10.


Previous studies suggested that licorice possessed hypoglycemic activity, but its anti-diabetic mechanism has not been clearly illustrated. Herein, we aimed to investigate the hypoglycemic activity and underlying hypoglycemic mechanisms of licorice extract (20, 40, and 80 mg kg-1day-1) in type 2 diabetes mice. The results showed that licorice extract could improve the levels of fasting blood glucose, insulin resistance, serum lipids, and endotoxemia-related colonic inflammation in diabetic mice in a dose-dependent manner. Western blots also suggested that a high-dose licorice extract could effectively decrease the levels of nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), and tumor necrosis factor-α (TNF-α) in colon of diabetic mice. More importantly, all the doses of licorice extract reshaped the gut microbiota by decreasing the contents of Lachnospiraceae_NK4A136_group at the genus level and increasing the contents of Alloprevotella, Bacteroides, and Akkermansia, especially for the high-dose of licorice extract. These results indicated that the anti-diabetic effect of licorice extract might be attributed to the regulation of the gut microbiota and the colon TLR4/NF-κB signaling pathway in diabetic mice. Thus, licorice extract can be a promising dietary agent to improve type 2 diabetes.

Keywords: Gut microbiota; Licorice extract; TLR4/NF-κB signaling pathway; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Type 2* / drug therapy
  • Gastrointestinal Microbiome*
  • Glycyrrhiza* / metabolism
  • Hyperglycemia* / drug therapy
  • Mice
  • NF-kappa B / metabolism
  • Plant Extracts / pharmacology
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism


  • NF-kappa B
  • Plant Extracts
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4