The PPAR activator puerarin reduces pro‐inflammatory lipids, potentially underlying its ability to improve insulin sensitivity and glucose metabolism

Puerarin, a unique C‐glucoside from kudzu root, is a potent anti‐hyperglycemic agent, but its molecular mechanisms are unidentified. In vitro studies indicate that puerarin activates PPARγ in human embryonic kidney cells (optimal at a100 nM).PPAR‐directed gene expression is significantly evaluated in a cell culturemodel, e.g., several genes such as fatty acid transport protein, carnitine palmotoyltransferase, acyl‐CoA oxidase and medium chain acyl‐CoA dehydrogenase are up‐regulated in cardiac cells following puerarin treatment. These results suggest that puerarin may activate PPARs and increase expression of target genes. In ob/ob mice, dietary administration of kudzu root extract (~23% puerarin) reduced LDL and two pro‐inflammatory lipids, ceramides and lysophosphatidylcholine in adipose tissue and hepatocytes. It also improved hyperglycemia and insulin sensitivity. The ob/ob mice (vs. controls) displayed a higher concentration of ceramides in adipose tissue, and chronic treatment with kudzu reduced ceramide levels in ob/ob adipocytes. Also, kudzu extract decreased plasma LDL concentration and the adipose tissue contained significant levels of puerarin. Ceremides are potent inhibitors of insulin receptor subunit 1, and thus the puerarin‐induced reduction of ceramides in ob/ob mice may play an important role in improved glucose tolerance and insulin sensitivity in this model.