Protocatechuic Acid Ameliorated Palmitic-Acid-Induced Oxidative Damage in Endothelial Cells through Activating Endogenous Antioxidant Enzymes via an Adenosine-Monophosphate-Activated-Protein-Kinase-Dependent Pathway

Protocatechuic acid (PCA, 3,4-dihydroxybenzoic acid), the main metabolite of anthocyanins, is widely distributed in fruits and vegetables and has been reported to possess a strong antioxidant activity. Herein, we aimed to investigate the protective effect of PCA against high palmitic-acid (PA)-induced oxidative damage and the underling molecular mechanisms in human umbilical vein endothelial cells (HUVECs). PCA reduced the levels of intracellular reactive oxygen species and malondialdehyde and increased the activities of endogenous antioxidant enzymes, including superoxide dismutase, glutathione peroxidase 1, and heme oxygenase 1 (HO-1). Metabolomic analysis showed that PCA affected numerous metabolites, especially some of which were related with energy metabolism. PCA also upregulated the phosphorylation of adenosine-monophosphate-activated protein kinase (AMPK) at Thr(172) through activating liver kinase B1 and then promoted the expression of p-Nrf2 and HO-1. Moreover, PCA reversed the decreased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and significantly increased the mitochondrial density. Collectively, these results demonstrated that PCA attenuated PA-induced oxidative damage in HUVECs via an AMPK-dependent pathway.