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The early myocardial response of hypertension is an elevation of angiotensin-II (Ang-II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT-R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti-inflammatory and anti-oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang-II-induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang-II 1 μM for 24 h to induce cellular damage. We found that EA protected against Ang-II-increased cell surface area and pro-hypertrophic gene expression in H9c2. EA reduced Ang-II-caused AT-R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang-II-enhanced p38 and extracellular-signal-regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang-II stimulation also reversed NF-κB activity and iNOS expression. This study shows that EA protects against Ang-II-induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang-II-induced myocardial hypertrophy., (© 2024 Wiley Periodicals LLC.)

Although the height of the proliferating layer that was suppressed in the growth plate has been recognized as an adverse effect of cisplatin in pediatric cancer survivors, the detailed pathological mechanism has not been elucidated. Sirtuin-1 (SIRT1) has been reported as an essential modulator of cartilage homeostasis, but its role in cisplatin-induced damage of chondrocytes remains unclear. In this study, we examined how cisplatin affected the expression of SIRT1 and cell viability. Next, we showed downregulation of SIRT1 after cisplatin treatment resulted in suppression of Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), leading to inhibition of Nrf2 nuclear translocation and subsequently decreased Heme oxygenase-1(HO-1) and NAD(P)H Quinone Dehydrogenase 1(NQO-1) expression. Blockage of the SIRT1/ PGC-1α axis not only increased oxidative stress with lower antioxidant SOD and GSH, but also contributed to mitochondrial dysfunction evidenced by the collapse of membrane potential and repression of mitochondrial DNA copy number and ATP. We also found that Cisplatin up-regulated the p38 phosphorylation, pro-inflammatory events and matrix metalloproteinases (MMPs) in chondrocytes through the SIRT1-modulated antioxidant manner. Collectively, our findings suggest that preservation of SIRT1 in chondrocytes may be a potential target to ameliorate growth plate dysfunction for cisplatin-receiving pediatric cancer survivors., (© 2023 Wiley Periodicals LLC.)

Atherosclerotic lesions play a critical role in leading cardiovascular diseases. Oxidized low-density lipoprotein (OxLDL) is a vital risk factor for atherosclerosis since it acts a crucial role in endothelial dysfunction and foam cell formation. Schisanhenol, a composition extracted from the fruit of Schisandra rubriflora, has been reported to have antioxidative effects on human LDL oxidation. This study investigates whether Schisanhenol protects against oxLDL-mediated endothelial damage by modulating the lectin-like oxLDL receptor-1 (LOX-1)-mediated inflammatory processes. Human umbilical vein endothelial cells (HUVECs) were pre-treated with 10 or 20 μM Schisanhenol for 2 h and then exposed to 150 μg/mL oxLDL. We revealed that Schisanhenol reduced oxLDL-enhanced LOX-1 expression. We also found that oxLDL down-regulated endothelial nitric oxide synthase (eNOS) as well as activated inducible NOS (iNOS), thereby enhancing the generation of nitric oxide (NO). Moreover, oxLDL elevated the expression levels of phosphorylated-p38MAPK, subsequently promoting NF-κB-modulated inflammatory responses. Pretreatment with Schisanhenol exerted significant cytoprotective function in all the above-mentioned detrimental events. Results from this present study reveal that Schisanhenol has a potential therapeutic effect on preventing oxLDL-induced endothelial injuries., (© 2023 Wiley Periodicals LLC.)

Osteoarthritis (OA) is a common degenerative joint disease. The pathological changes of chondrocytes involve oxidative stress, the pro-inflammatory response, and pro-apoptotic events. Galectin-3 (Gal-3) is a 35 kDa protein with a special chimeric structure. Gal-3 participates in the progression of many diseases, such as cancer metastasis and heart failure. A previous study demonstrated that Gal-3 expression in human cartilage with OA is increased. However, the role of Gal-3 in chondrocyte dysfunction in joints is still unclear. In this study, we applied Gal-3 (5-20 μg/ml) to TC28a2 human chondrocyte cells for 24 h to induce chondrocyte dysfunction. We found that Gal-3 upregulated TLR-4 and MyD88 expression and NADPH oxidase, thereby increasing intracellular ROS in the chondrocytes. Gal-3 increased phosphorylated MEK1/2 and ERK levels, and promoted NF-κB activity. This activation of NF-κB was reduced by silencing TLR-4 and NOX-2. In addition, Gal-3 caused apoptosis of chondrocytes through the mitochondrial-dependent pathway via the TLR-4/NADPH oxidase/MAPK axis. Our study proves the pathogenic role of Gal-3 in Gal-3-induced chondrocyte dysfunction and injuries., (© 2021 Wiley Periodicals LLC.)

Peripheral arterial disease (PAD) affects more than 200 million people worldwide. Recent studies suggest that oxidative stress-related inflammation can lead to the initiation and progression of PAD. Ferulic acid (FA) is a natural phenolic compound and has been proven to have antioxidant and angiogenesis effects. In this study, thermosensitive chitosan-gelatin-based hydrogel was used as a delivery vehicle of FA. The effects of hydrogel encapsulating FA (FA-gel) have been demonstrated in vitro and in vivo. The results revealed that the developed hydrogel with porous structure could provide a sustained release of FA. Post-treatment of FA-gel effectively decreased the oxidative stress-induced damage in human umbilical vein endothelial cells via decreasing endogenous reactive oxygen species production, inflammation-related gene expression and apoptosis level. In the mouse hindlimb ischemia model, the results revealed that FA-gel could improve blood flow, muscle regeneration and decreases inflammation in veins. These results suggested that FA-gel may have a therapeutic potential in PAD., (© 2020 John Wiley & Sons, Ltd.)

Non-small cell lung cancer (NSCLC) is often complicated by pulmonary infection, which affects treatment and prognosis. Bacterial lipopolysaccharide (LPS) is an effective stimulator of inflammatory cytokine production, and previous studies have reported that LPS promotes tumor invasion and metastasis. Mangiferin is a plant-derived C-glucosylxanthone with many biological activities, such as antioxidation and anti-inflammation. This research mainly explored the mechanism of its antitumor activities on LPS-induced A549, NCI-H460, and NCI-H520 NSCLC cells. We determined that mangiferin exhibits growth inhibiting activity against LPS-induced NSCLC cells through the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. In addition, mangiferin reversed the LPS-induced downregulation of E-cadherin (epithelial marker); conversely, it significantly inhibited the expression of raised vimentin (mesenchymal markers). Moreover, the ability of NSCLC cells to migrate, as evidenced by the wound healing and transwell migration assays, and the expression of CXCR4 increased by LPS were significantly repressed by mangiferin. In addition, mangiferin markedly mediated protein levels of PER1 and NLRP3 in LPS-induced NSCLC cells and reduced the secretion of IL-1β. These results indicate that mangiferin is not only a remarkable anti-inflammatory compound but also an antitumor agent; thus, it has the potential for being developed into anti-inflammatory and antitumor drugs in the future., (© 2020 Wiley Periodicals LLC.)

Galectin-3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin-3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1), a receptor for oxLDL uptake, contributes to oxLDL-induced endothelial dysfunction. Whether galectin-3 induces endothelial dysfunction through modulation of LOX-1-mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin-3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX-1. Incubation of HUVECs with galectin-3 increased the expression of LOX-1 in RNA and protein levels. In addition, the expression of LOX-1 induced by oxLDL was promoted by galectin-3. However, pretreatment of LOX-1 antibody reduced LOX-1 mRNA expression level in cells with oxLDL plus galectin-3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen-activated protein kinases followed by nuclear factor kappa B (NF-κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL-8 release were also aggravated in cells treated with galectin-3 combined with oxLDL. Compared to cells treated with galectin-3 plus oxLDL group. We found that LOX-1 antibody mitigated NADPH oxidase activity, p-38 up-regulation, NF-κB activation, and proinflammatory responses in cells treated with galectin-3 combined with oxLDL. We conclude that galectin-3 enhances endothelial LOX-1 expression and propose a new mechanism by which galectin-3 may promote endothelial dysfunction by inducing inflammation via LOX-1/ROS/p38/NF-κB-mediated signaling pathway., (© 2019 Wiley Periodicals, Inc.)