Anethum graveolens L. restores expression of free fatty acid synthesis-related genes in high fat induced-HepG2 cells

Introduction: The ethanolic extract of Anethum graveolens (dill) and its major constituents, chlorogenic acid (CGA) and ellagic acid (EA), were investigated for hepatoprotective effects in a HepG2 cell fatty liver model. Methods: HepG2 cells were induced with a combination of oleic (1mM OA) and palmitic (1mM PA) acids and treated with either 10 mu M fenofibrate, 1-10 mu g/mL CGA or EA, 60-360 mu g/mL A. graveolens extract, or left untreated (n=4-5 per group). After 48 hours, cell medium and cells were collected for alanine transaminase (ALT), aspartate transaminase (AST), reactive oxygen species (ROS), and fatty acid accumulation assays. The mRNA and protein expression levels of free fatty acid (FFA) synthetic pathway-related genes were determined using reverse transcription/real-time polymerase chain reaction and Western blotting analysis, respectively. Results: HepG2 cells treated with OA and PA showed increased ALT, AST, and ROS levels, fatty acid accumulation, and modified mRNA and protein expression of PPAR, SREBP1, ACC, ACOX, FAS, SCD1, and HMGCR fatty acid synthesis-related genes. The CGA, EA, and A. graveolens extract showed hepatoprotective activities in OA and PA-induced HepG2 cells by preventing fatty acid accumulation and restoring mRNA and protein expression levels of the fatty acid synthesis-related genes to control levels, with comparable efficacy to the standard antilipidemic drug, fenofibrate. Furthermore, CGA, EA, and A. graveolens extract did not increase ALT and ROS levels in HepG2 cells, in contrast to fenofibrate. Conclusion: A. graveolens extract, CGA, and EA are good candidates for development as preventive health supplements for fatty liver disease therapy.