Punicalin Alleviates OGD/R-Triggered Cell Injury via TGF-β-Mediated Oxidative Stress and Cell Cycle in Neuroblastoma Cells SH-SY5Y

Abstract

Purpose. The research aimed to identify the active component from Punica granatum L. to alleviate ischemia/reperfusion injury and clarify the underlying mechanism of the active component alleviating ischemia/reperfusion injury. Materials and Methods. The SH-SY5Y cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) was established to simulate the ischemia/reperfusion injury. According to the strategy of bioassay-guided isolation, the active component of punicalin from Punica granatum L. was identified. Flow cytometry and Western blotting were employed to evaluate the effects of OGD/R and/or punicalin on cell cycle arrest. Immunofluorescence assay was applied to assess the nucleus translocation. The relative content of ROS and GSH and the enzyme activities of CAT and SOD were examined using ELISA. Results. The data of bioassay-guided isolation showed that punicalin from Punica granatum L. could alleviate OGD/R-induced cell injury in SH-SY5Y cells. Flow cytometry analysis and Western blotting for probing the expression of CDK1, p-CDK1, cyclin B1, and p21 revealed that punicalin could relieve OGD/R-induced cell cycle G0/G1 arrest. Additionally, immunofluorescence assay and Western blotting for probing the expression of TGF-β and p-Smad2/p-Smad3 showed that punicalin could relieve the OGD/R-induced TGF-β/Smad pathway. Furthermore, the TGF-β/Smad pathway inhibitor of LY2157299 was employed to confirm that the TGF-β/Smad pathway is crucial to the effect of punicalin. At last, it was indicated that punicalin could relieve OGD/R-induced oxidative stress. Conclusion. Punicalin, an active component from Punica granatum L., was identified as a protective agent to alleviate the OGD/R-induced cell injury, which could exert the protective effect via TGF-β/Smad pathway-regulated oxidative stress and cell cycle arrest in SH-SY5Y cells.

Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

“…TGF expression was increased in an undifferentiated SH-SY5Y cell model of cerebral ischemia, together with increased phosphorylation of SMAD2 and SMAD3. Ischemia/hypoxia promoted translocation of SMAD3 from the cytoplasm to the nucleus (Yang et al 2021b ).…”

“…Oxidative/nitrosative stress was investigated as a treatment target in twenty studies using undifferentiated SH-SY5Y cells and one study using differentiated SH-SY5Y cells. These studies showed that various chemical compounds could reduce oxidative stress by reducing the formation of ROS or increasing anti-oxidant defense mechanisms, which led to increased cell survival (Agudo-Lopez et al 2010 ; Chen et al 2021b ; Dong et al 2021 ; Gao et al 2017 ; Hong et al 2017 ; Hsieh et al 2021 ; Jimenez-Almarza et al 2019 ; Landgraf et al 2020 ; Li et al 2020a ; Liu et al 2019a ; Liu 2016 ; Marutani et al 2012 ; Park et al 2017 ; Ruan et al 2021 ; Shi et al 2019 ; Sriwastva et al 2020 ; Wang et al 2019b ; Wu et al 2020a ; Xu et al 2020b ; Yang et al 2021b ; Zhi et al 2020 ).…”

Ursolic acid protects against anoxic injury in cardiac microvascular endothelial cells by regulating intercellular adhesion molecule-1 and toll-like receptor 4/MyD88/NF-κB pathway

“…26 Several drugs, such as dioxin, alpha-tocopherol, and irisin, have protective effects on I/R injury through oxidative stress. 27,28 A large number of studies have shown that oxidative stress injury of microcirculation, especially oxidative stress of CMECs during reoxygenation, is the main factor regulating the incidence of myocardial ischemia. 29 Interestingly, in our study, we discovered that UA alleviated the damage of H/R induced-CMECs by regulating the oxidative stress, that is, the protein levels of SOD, CAT, and GSH-Px were down-regulated in CMECs stimulated by H/R, which was suppressed by UA or/and si-ICAM1 treatment.…”

The Antimicrobial Effect of Pomegranate Peel Extract versus Chlorhexidine in High Caries Risk Individuals Using Quantitative Real-Time Polymerase Chain Reaction: A Randomized Triple-Blind Controlled Clinical Trial

“…[4] A noninvasive ecological stratagem, propelling natural products into the cariological verse in a bid to deliver potentially active cariostatic catalytic agents in the form of mouthwashes, gels, varnishes, or chewing gums have been adopted, researched, and enforced in order to proselytize cariogenic microbial demise [5,6]. Of all known natural products researched to date, the pomegranate, which possesses nutritional and medicinal health benefits galore, has the capacity to vehemently respond to a plethora of human oral and/or systemic illnesses [7][8][9].…”