The Protective Effect of Aspirin Eugenol Ester on Oxidative Stress to PC12 Cells Stimulated with H₂O₂ through Regulating PI3K/Akt Signal Pathway

Abstract

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. This study is aimed at identifying the protective effect of AEE against H2O2-induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. The results of cell viability assay showed that AEE could increase the viability of PC12 cells stimulated by H2O2, while AEE alone had no significant effect on the viability of PC12 cells. Compared with the control group, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly decreased, and the content of malondialdehyde (MDA) was significantly increased in the H2O2 group. By AEE pretreatment, the level of MDA was reduced and the levels of SOD, CAT, and GSH-Px were increased in H2O2-stimulated PC12 cells. In addition, AEE could reduce the apoptosis of PC12 cells induced by H2O2 via reducing superoxide anion, intracellular ROS, and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential (ΔΨm). Furthermore, the results of western blotting showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of Caspase-3 and Bax was significantly increased in the H2O2 group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of Caspase-3 and Bax in PC12 cells stimulated with H2O2. The silencing of PI3K with shRNA and its inhibitor-LY294002 could abrogate the protective effect of AEE in PC12 cells. Therefore, AEE has a protective effect on H2O2-induced PC12 cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.

Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling

“…In this study, we also found GC inhibited the expression of SOD1, SOD2, GR, GPX1, and CAT to activate oxidative stress. According to other reports, GDF15/AKT/mTOR signaling is closely related to oxidative stress, wherein the activation of this signaling could suppress ROS accumulation [ 19 – 21 , 23 , 29 , 48 , 49 ]. In our study, D7 treatment was observed to inhibit the GC-induced oxidative stress by restoring the expression levels of SOD1, SOD2, CAT, and GPX.…”

“…Moreover, for several other types of cells, the AKT/mammalian target of rapamycin (mTOR) pathway acts downstream of GDF, and GDF15 could promote the survival and proliferation of cells via the activation of AKT/mTOR signaling pathway [26][27][28]. At the same time, the AKT/mTOR signaling pathway is closely associated with ROS, as its activation protects cells from ROS accumulation and restores the balance of ROS [29,30]. Nonetheless, the mechanisms through which GDF15/AKT/ mTOR signaling mediates the pathophysiological changes in association with SONFH and whether this signaling pathway can restore the redox balance in BMSCs under GC conditions are largely unknown.…”

Effect of tramadol on liver enzymes, oxidative stressm and some antioxidant markers in male rabbits

“…Under normal physiological conditions, the antioxidant enzymes work to maintain the redox balance of the body and neutralize rampaging free radical and thus reducing its capacity to damage. They act as radical scavenger, hydrogen donor, electron donor, peroxide decomposer, singlet oxygen quencher, and synergist (23)(24)(25) . At the molecular levels, glutathione system is the mother of all antioxidants, the master detoxifier and maestro of the immune system.…”

Synthesis of Quercetin‐Acid Esters and Its Reduction of H2O2‐Triggered PC12 Cells Damage by Down‐Regulating ROS

“…When cells are stimulated by H 2 O 2 , oxidative stress occurs, and the body produces too much highly reactive molecules such as reactive oxygen species (ROS). ROS in the body mainly include hydroxyl radicals, superoxide anions and singlet oxygen [28,29] . Excessive production of ROS is one of the main causes of oxidative stress [30,31] .…”

“…ROS in the body mainly include hydroxyl radicals, superoxide anions and singlet oxygen. [28,29] Excessive production of ROS is one of the main causes of oxidative stress. [30,31] Normal levels of ROS help maintain normal cellular function.…”