Protective Effects of (E)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeine Against Hydrogen Peroxide-Induced Injury in PC12 Cells

Abstract

(E)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeine (HOEC), a naturally caffeic ester isolated from Incarvillea mairei, has been reported to possess anti-inflammatory activity by targeting 5-lipoxygenase. However, its other potential activities have yet to be explored. In this study, we measured antioxidant activity of HOEC using the DPPH free radical-scavenging assay. Then, we exposed rat pheochromocytoma (PC12) cells to hydrogen peroxide (H2O2)-induced damage and investigated the antioxidant activity of HOEC. Cell viability, lactate dehydrogenase (LDH) release, cellular morphology, Hoechst 33342 fluorescent staining, and apoptosis of the PC12 cells were assessed after treatment with 0.3-10 μM HOEC for 2 h and exposure to 600 μM H2O2. Additionally, glutathione reductase (GR), superoxide dismutase (SOD), lipid peroxidation malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) accumulation were assayed after the PC12 cells were exposed to H2O2. To investigate mechanism, apoptosis-related protein were evaluated, including cleaved caspase 3/7, cleaved PARP, Bcl-2, Bcl-XL, and cytochrome c. The results showed that HOEC possessed potent antioxidant activity and pre-treatment with HOEC prior to H2O2 exposure significantly increased cell viability, reduced the release of LDH, ameliorated changes in cell morphology, and inhibited apoptosis. Further, HOEC did the following: reduced intracellular accumulation of ROS and MDA; rescued loss of SOD and GR activities; inhibited activated caspase-3 and caspase-7, cleaved PARP, and cytochrome c release; up-regulated the antiapoptosis-related protein Bcl-2 and Bcl-XL; and down-regulated the apoptosis-related proteins Bax and Bad. These findings suggested that HOEC may be a therapeutic agent for treating oxidative stress-derived neurodegenerative disorders.

Propofol Protects Against H2O2-Induced Oxidative Injury in Differentiated PC12 Cells via Inhibition of Ca2+-Dependent NADPH Oxidase

“…However, the focus of our work is to investigate the effects of propofol against oxidative stressrelated neurological disorders and the underling mechanisms, which is very different from Hsu'work, and this is also the major contribution of our work. In our current study, the rat differentiated PC12 cell was subjected to H 2 O 2 exposure to mimic a neuronal in vitro model of oxidative injury, previous researches (Hwang and Yen 2008;Li et al 2013;Wei et al 2014;Chen et al 2014) have demonstrated that the concentration of H 2 O 2 selected (250 lM) in our study is within the concentration range of H 2 O 2 typically identified in neurological disorders. We found that propofol-induced attenuation of NOX2 expression and NOX activity is involved in its cytoprotective effects against H 2 O 2 -induced oxidative injury in PC12 cells.…”

Protective functions of salvianolic acid B in PC-12 cells against hydrogen peroxide-triggered damage by mediation of microRNA-26a

“…Previous study corroborated that miRNAs play critical roles in various ailments which are linked to oxidative damage [30]. MiR-26a is a crucial miRNA, which has been reported in multitudinous cancers [31,32] The mitochondria-dependent apoptotic pathway has been disclosed to join in H 2 O 2 -triggered cytotoxicity in PC-12 cells [34]. It has been testified that PI3K/AKT and MEK/ERK pathways are the dominating pro-survival pathways within the cells [35].…”

Neuroprotective effects of Liriope platyphylla extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SH-SY5Y cells

“…Previous papers reported that H 2 O 2 had cytotoxic effects in various in vitro model by a mechanism involving pro-apoptotic factors (Bax, caspases, PARP) activation and intracellular signaling pathway [ 45 – 51 ]. Especially, MAPK signaling pathway has been suggested as an important mechanism in oxidative stress-mediated neurodegenerative diseases [ 52 , 53 ].…”