Theaflavin TF3 relieves hepatocyte lipid deposition through activating AMPK signaling pathway by targeting plasma kallikrein

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of chronic liver diseases throughout the world. The deficit of pharmacotherapy for NAFLD calls for an urgent need of new drug discovery and lifestyle management. Black tea is the most popular, and functional drink consumed worldwide. Its main bioactive theaflavin helps prevent obesity-a major risk factor for NAFLD. To find new targets for the development of effective and safe therapeutic drugs from natural plants for NAFLD, we found theaflavin monomer theaflavin-3, 3'-digallate (TF3) significantly reduced lipid droplet accumulation in hepatocytes, and directly bound and inhibited the activation of plasma kallikrein (PK), which was further proved to stimulate adenosine monophosphate activated protein kinase (AMPK) and its downstream targets. Taken together, we proposed that the TF3-PK-AMPK regulatory axis is a novel mechanism of lipid deposition mitigation, and PK could be a new target for NAFLD treatment.