Amorfrutins are potent antidiabetic dietary natural products

Proc Natl Acad Sci U S A. 2012 May 8;109(19):7257-62. doi: 10.1073/pnas.1116971109. Epub 2012 Apr 16.


Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Biological Products / chemistry
  • Biological Products / metabolism
  • Biological Products / pharmacology*
  • Blotting, Western
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Crystallography, X-Ray
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / etiology
  • Diet, High-Fat / adverse effects
  • Dietary Supplements
  • Fabaceae / chemistry*
  • Gene Expression / drug effects
  • Glycyrrhiza / chemistry
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Obesity / complications
  • Obesity / drug therapy
  • Obesity / etiology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salicylates / chemistry
  • Salicylates / metabolism
  • Salicylates / pharmacology*


  • Biological Products
  • Hypoglycemic Agents
  • PPAR gamma
  • Salicylates

Associated data

  • GEO/GSE28384
  • PDB/2YFE