Protocatechuic acid protects hepatocytes against hydrogen peroxide-induced oxidative stress

Oxidative stress is a main cause of tissue damage and highly associated with incidence of human chronic diseases. Among the major target organs attacked by reactive oxygen species (ROS) is the liver. Protocatechuic acid (PCA) is a phenolic compound found in green tea, acai oil and some mushroom species that possesses strong antioxidative and anti-inflammatory activity and may have benefits as a natural phytochemical for prevention of human diseases. However, the protective effect of PCA on hydrogen peroxide (H₂O₂)-induced oxidative stress specifically in the liver has not yet been investigated. The current study aims to observe if PCA possesses protective activity against H₂O₂-induced oxidative stress in HepG2 human liver cancer cells. Relative to untreated control cells, treatment of HepG2 cells with PCA reduced H₂O₂-induced cell death and mitigated H₂O₂-induced production of ROS; furthermore, it mitigated the H₂O₂-induced increase of caspase-3/7 enzyme activity, expression of cleaved poly(ADP-ribose) polymerase (PARP), expression of endoplasmic reticulum (ER) stress genes including activating transcription factor 4 (ATF4), serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α (IRE1α) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). These findings indicate that PCA effectively protects hepatic cells from H₂O₂-induced oxidative stress and cell death.