Abstract
Objectives
The non-alcoholic fatty liver disease (NAFLD) comprises the broad histopathological states of liver, that ranging from asymptomatic hepatic steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. In some studies, they suppose that almost 25–30% of world population is underlying NAFLD. Lemon balm (Melissa officinalis) is the herb that has some traditional medicinal usages. Also rosmarinic acid (RA; O-caffeoyl-3,4-dihydroxyphenyl lactic acid), the major chemical compound of lemon balm, already reported that it has the potency on anti-obesity and -inflammatory. Hence, we evaluate the whether lemon balm extract (LBE) and RA could suppress the pathogenesis of NASH using an in vitro and in vivo model.
Methods
In vitro model: The palmitic acid (PA) exposed HepG2 hepatocellular carcinoma cells can imitate the lipid accumulation in hepatocytes. PA exposed HepG2 cells were exposed with or without LBE or RA.
In vivo model: The methionine- and choline-deficient (MCD) diet fed db/db C57BL/6 J mice model was used. This model is known as it can mimic well symptoms of human NAFLD. The LBE or RA were treated by oral gavage.
Results
With the MCD diet only, the severe liver damage was caused by progression of NASH in animal model. LBE and RA treatments alleviated the oxidative stress in the MCD diet-fed db/db mice and PA-exposed HepG2 cells by increasing the expression of antioxidant enzymes (NRF2, SOD) and augmented lipolysis-related gene (PPARα, PGC-1α, CPT-1 L) expression. In addition, LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis (α-SMA, COL1A1) and fatty acid synthesis (SREBP-1c, CPT-1 L) and activated AMP-activated protein kinase in vitro and in vivo. Also, the histopathological results were ameliorated by treatment of LBE or RA.
Conclusions
LBE and RA modulate lipid metabolism via AMPK activation and suppress inflammation via changes in NRF2 and NF-κB signalling. Importantly, the extract of lemon balm obtained with 20% EtOH showed effectiveness similar to that of RA at high concentrations. Therefore, LBE may be a good candidate for the treatment and prevention of NASH.
Funding Sources
This work was supported by the National Research Council of Science & Technology (NST) funded by the Korea Government (MSIP) (grant No. CRC-15-01-KIST).
Supporting Tables, Images and/or Graphs
