Lemon Balm and Its Constituent, Rosmarinic Acid, Alleviate Liver Damage in an Animal Model of Nonalcoholic Steatohepatitis

Nutrients. 2020 Apr 22;12(4):1166. doi: 10.3390/nu12041166.


Nonalcoholic fatty liver disease (NAFLD) ranges in severity from hepatic steatosis to cirrhosis. Lemon balm and its major constituent, rosmarinic acid (RA), effectively improve the liver injury and obesity; however, their therapeutic effects on nonalcoholic steatohepatitis (NASH) are unknown. In this study, we investigated the effects of RA and a lemon balm extract (LBE) on NAFLD and liver fibrosis and elucidated their mechanisms. Palmitic acid (PA)-exposed HepG2 cells and db/db mice fed a methionine- and choline-deficient (MCD) diet were utilized to exhibit symptoms of human NASH. LBE and RA treatments alleviated the oxidative stress by increasing antioxidant enzymes and modulated lipid metabolism-related gene expression by the activation of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis and inflammation in vitro and in vivo. Together, LBE and RA could improve liver damage by non-alcoholic lipid accumulation and may be promising medications to treat NASH.

Keywords: AMP-activated protein kinase (AMPK); anti-inflammation; antioxidants; lemon balm extract (LBE); nonalcoholic steatohepatitis (NASH); rosmarinic acid (RA).

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Cells, Cultured
  • Cinnamates / isolation & purification
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use*
  • Depsides / isolation & purification
  • Depsides / pharmacology
  • Depsides / therapeutic use*
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism / drug effects
  • Liver / metabolism
  • Male
  • Melissa / chemistry*
  • Mice, Inbred Strains
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oxidative Stress / drug effects
  • Phytotherapy*


  • Cinnamates
  • Depsides
  • AMP-Activated Protein Kinases
  • rosmarinic acid