Effects of Plant Phenolic Compounds on Ethanol-Induced Hepatocyte Damage: A Comparative Study

Background: Previous studies have shown the beneficial effects of phenolic compounds on liver disorders. In the present study, the effects of eight phenolic compounds— chlorogenic acid, curcumin, gallic acid, hesperidin, resveratrol, rosmarinic acid, silibinin, and silymarin—on ethanol-induced cytotoxicity were investigated both individually and in combination.
Methods: The HepG2 liver cell line and primary rat liver-derived cells were cultured in the presence of ethanol (7% v/v) and different concentrations of phenolic compounds. We used different incubation designs, including co-incubation and pre-incubation, and varied incubation times to investigate the effect of these compounds on alcohol-induced cytotoxicity.
Results: Incubation of HepG2 cells and primary liver cells for 4 hours with ethanol significantly decreased their viability (p < 0.001). Pre-incubation and co-incubation with concentrations of 3-50 μM of chlorogenic acid, curcumin, gallic acid, resveratrol, rosmarinic acid, silibinin, or silymarin did not restore cell viability. Only hesperidin at 12.5 μM showed a mild but statistically significant (p < 0.05) protective effect in HepG2 cells. Binary combinations of curcumin, silibinin, and resveratrol at 12.5 μM did not show additive or synergistic activity against ethanol cytotoxicity after 4 hours. Additionally, combinations of chlorogenic acid, hesperidin, rosmarinic acid, and silymarin did not induce additive or synergistic activities after 6 hours.
Conclusion: The phenolic compounds tested did not exhibit significant cytoprotective effect in the model of ethanol-induced acute toxicity used in the present study. Conducting further research using different study designs—such as chronic toxicity models or lower ethanol concentrations—might yield different results.