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

Abstract

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 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 γ coactivator 1α and significantly increased the mitochondrial density. Collectively, these results demonstrated that PCA attenuated PA-induced oxidative damage in HUVECs via an AMPK-dependent pathway.

Protocatechuic acid inhibits testicular and epididymal toxicity associated with methotrexate in rats

“…The marked increase in the testicular and epididymal levels of RONS and MDA following MTX administration observed in this study corroborates earlier reports attributed to oxidative stress in MTX‐mediated toxic injury (Najafi, Atashfaraz, & Farokhi, ) (Heidari et al, ). RONS and MDA levels in rats administered MTX and PCA were markedly reduced by the presence of PCA, which can be associated with PCA antioxidant properties as earlier reported (Han et al, ; Safaeian, Emami, Hajhashemi, & Haghighatian, ).…”

Protective effects of phenolic acid extract from ginseng on vascular endothelial cell injury induced by palmitate via activation of PI3K/Akt/eNOS pathway

“…Collectively, these events distruct the function of insulin and induce endothelial injury and dysfunction (Khan et al., 2012; King, Park, & Li, 2016). Over the past decade, numerous active components have been screened from plants using an in vitro cellular model based on PA‐treated endothelial cells for FFA‐induced endothelial dysfunction (Han et al., 2018; Li et al., 2018; Ma et al., 2019; Shi et al., 2019).…”

Different Phenolic Extracts of Oil Palm Fruits and Caffeic Acid Prevent Palmitic Acid-Induced Lipotoxicity in HepG2 Cells via Improving Mitochondrial Function

“…In another study, 10 μM catechin can decrease 54% ROS generation in PAinduced HepG2 cells [28]. Moreover, it also found that protocatechuic acid could significantly attenuate ROS generation by activating endogenous antioxidant enzymes [29].…”

“…e mitochondrion is a crucial organelle, that not only undertakes the energy regulation but also controls the balance of ROS generation [9]. Under the condition of lipotoxicity, the massive ROS could rapidly diffuse to the mitochondrion, lead to MMP depolarization, and thereby mediate cell apoptosis [29,34].…”