scholarly journals Naringin attenuates cerebral ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress

2021 ◽  
Vol 12 (1) ◽  
pp. 190-197
Author(s):  
Li Wang ◽  
Zhe Zhang ◽  
Haibin Wang
Keyword(s):  
Endoplasmic Reticulum ◽  
Brain Tissue ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Tissue Water Content ◽  
Tissue Water ◽  
Concentration Dependent Manner ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Related Proteins

Abstract Objective This investigation was carried out with an aim of exploring neuroprotection by naringin (Nar) in rats with cerebral ischemia-reperfusion (CI/R) injury and its mechanism. Methods Rats were grouped into ischemia-reperfusion (I/R), sham operation (Sham), nimodipine control (NIM), and different doses of Nar (Nar-L, Nar-M, Nar-H) groups. With Zea Longa score for assessment of neurological deficits, dry and wet method for measurement of brain tissue water content, and (2,3,5-triphenyltetrazolium chloride) TTC staining for determination of cerebral infarction volume, the related parameters were obtained and compared. Subsequently, ELISA was introduced to detect levels of proinflammatory cytokines (TNF-α, IL-8) and anti-inflammatory cytokine (IL-10) in the serum as well as superoxide dismutase (SOD) and malondialdehyde (MDA) activities in brain tissue. Western blot was applied to evaluate endoplasmic reticulum stress (ERS)-related proteins expression, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12, and activating transcription factor 6 (ATF-6). Results Nar significantly alleviated nerve injury and decreased brain tissue water content and brain infraction volume in CI/R injury rats in a concentration-dependent manner. Reduction of TNF-α, IL-8 as well as MDA content and elevation of IL-10 as well as SOD activity were confirmed to be caused by Nar treatment in a concentration-dependent manner. Meanwhile, ERS-related proteins also markedly decreased in the Nar groups. Conclusion Nar may achieve neuroprotection and alleviation of CI/R injury by anti-inflammation, anti-oxidation, and inhibiting ERS, and its efficacy is concentration-dependent.

scholarly journals Ghrelin Alleviates Endoplasmic Reticulum Stress in MC3T3E1 Cells by Inhibiting AMPK Phosphorylation

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xue Lv ◽  
Qianping Zhang ◽  
Bingfei Cheng ◽  
Ying Xin ◽  
Jun Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Energy Homeostasis ◽  
Marker Genes ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Expression Of Genes ◽  
Species Production ◽  
Related Proteins

Ghrelin is a gastric endocrine peptide that has been found to be involved in the process of energy homeostasis and bone physiology in recent years. To explore the effects of ghrelin on endoplasmic reticulum stress (ERS) in MC3T3E1 cells and its possible mechanism, an ERS model was induced by tunicamycin (TM) in the osteoblast line MC3T3E1. TM at 1.5 μg/mL was selected as the experimental concentration found by CCK8 assay. Through the determination of apoptosis, reactive oxygen species production, and endoplasmic reticulum stress-related gene expression, we found that ERS induced by TM can be relieved by ghrelin in a concentration-dependent manner ( P < 0.001 ). Compared with the TM group, ghrelin reduced the expression of ERS-related marker genes induced by TM. Compared with the GSK621 + TM group without ghrelin pretreatment, the mRNA expression of genes in the ghrelin pretreatment group decreased significantly ( P < 0.001 ). The results of protein analysis showed that the levels of BIP, p-AMPK, and cleaved-caspase3 in the TM group increased significantly, while the levels decreased after ghrelin pretreatment. In group GSK621 + TM compared with group GSK621 + ghrelin+TM, ghrelin pretreatment significantly reduced the level of p-AMPK, which is consistent with the trend of the ERS-related proteins BIP and cleaved-caspase3. In conclusion, ghrelin alleviates the ERS induced by TM in a concentration-dependent manner and may or at least partly alleviate the apoptosis induced by ERS in MC3T3E1 cells by inhibiting the phosphorylation of AMPK.

The protective effect of ligustrazine on rats with cerebral ischemia–reperfusion injury via activating PI3K/Akt pathway

2019 ◽  
Vol 38 (10) ◽  
pp. 1168-1177 ◽  
Author(s):  
Y Ding ◽  
J Du ◽  
F Cui ◽  
L Chen ◽  
K Li
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Ischemia Reperfusion ◽  
Pi3k Inhibitor ◽  
Akt Pathway ◽  
Control Group ◽  
Dependent Manner ◽  
Cerebral Ischemia Reperfusion ◽  
Dose Dependent

The study was to investigate the effects of ligustrazine on rats with cerebral ischemia–reperfusion (I/R) injury and to explore the potential mechanism. Transient focal cerebral ischemia Wistar rat model was established through middle cerebral artery occlusion. The cerebral I/R injury rats were treated with intraperitoneal injection of ligustrazine (1, 3, and 10 mg/kg). Human amniotic epithelial cells (HAECs) were treated with ligustrazine (1, 10, 100 μM) and PI3K inhibitor wortmannin (100 μM), following oxygen–glucose deprivation (OGD) treatment. The expression levels of protein kinase B (PKB or AKT), phospho-Akt (p-Akt), endothelial nitric oxide synthase (eNOS), and phosphor-eNOS (p-eNOS) in HAECs and brains of rats were measured by Western blot. The levels of nitric oxide (NO) in HAECs were measured by Griess method using NO2−/NO3− Assay Kit. Infarct volume and neurological deficits were evaluated 24 h after reperfusion. The levels of NO, p-Akt/Akt, and p-eNOS/eNOS in HAECs were significantly reduced after OGD, but ligustrazine treatment increased the levels of those factors in a dose-dependent manner, while those increases were reversed by PI3K inhibitor wortmannin. Similarly, p-Akt/Akt and p-eNOS/eNOS in brain tissue of rats with I/R were significantly reduced compared with control group ( p < 0.05), but ligustrazine treatment increased the levels of p-Akt and p-eNOS in a dose-dependent manner ( p < 0.05), while those increases were also reversed by using wortmannin. Ligustrazine also improved the damage of rat brain tissue caused by I/R, but wortmannin reversed the improvement. Ligustrazine plays a neuroprotective role in rats with cerebral I/R injury through the activation of PI3K/Akt pathway.

scholarly journals Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1545
Author(s):  
Hwa-Young Song ◽  
Da-Eun Jeong ◽  
Mina Lee
Keyword(s):  
Biological Activities ◽  
Radical Scavenging ◽  
No Production ◽  
Dependent Manner ◽  
Optimal Method ◽  
Concentration Dependent Manner ◽  
Osmanthus Fragrans ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Extracellular Regulated Kinase

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

scholarly journals Effects of irbesartan on phenotypic alterations in monocytes and the inflammatory status of hypertensive patients with left ventricular hypertrophy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jingsi Zhang ◽  
Lina Yang ◽  
Yanchun Ding
Keyword(s):  
Ventricular Hypertrophy ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Hypertensive Patients ◽  
Inflammatory Status ◽  
Tnf Α

Abstract Background Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension and the resulting target organ damage. In this study, we observed alterations in the monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and studied the effects of irbesartan in these patients. This study might reveal a novel mechanism by which irbesartan alleviates LVH, and it could provide new targets for the prevention and treatment of hypertensive target organ damage. Methods CD163 and CD206 expression on monocytes and IL-10 and TNF-α levels in the serum of hypertensive patients with or without LVH and of healthy volunteers were detected. Furthermore, we treated monocytes from the LVH group with different concentrations of irbesartan, and then, CD163, CD206, IL-10 and TNF-α expression was detected. Results We found, for the first time, that the expression of CD163, CD206 and IL-10 in the LVH group was lower than that in the non-LVH group and healthy control group, but the TNF-α level in the LVH group was significantly higher. Irbesartan upregulated the expression of CD163 and CD206 in hypertensive patients with LVH in a concentration-dependent manner. Irbesartan also increased the expression of IL-10 and inhibited the expression of TNF-α in monocyte culture supernatants in a concentration-dependent manner. Conclusions Our data suggest that inflammation was activated in hypertensive patients with LVH and that the monocyte phenotype was mainly proinflammatory. The expression of proinflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter the monocyte phenotype and inflammatory status in hypertensive patients with LVH. This previously unknown mechanism may explain how irbesartan alleviates LVH. Trail registration The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent form.

scholarly journals Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 123
Author(s):  
Natalia K. Kordulewska ◽  
Justyna Topa ◽  
Małgorzata Tańska ◽  
Anna Cieślińska ◽  
Ewa Fiedorowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Reaction ◽  
Wide Spectrum ◽  
Cell Monolayer ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

scholarly journals Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway

2021 ◽  
Vol 12 (1) ◽  
pp. 020-031
Author(s):  
Kong Fu ◽  
Miancong Chen ◽  
Hua Zheng ◽  
Chuanzi Li ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

Abstract 172: Thrombopoietin Receptor Agonists Protect Human Cardiac Myocytes from Injury by Activation of Cell Survival Pathways

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
John E Baker ◽  
Jidong Su ◽  
Stacy Koprowski ◽  
Anuradha Dhanasekaran ◽  
Tom P Aufderheide ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Survival Pathways ◽  
Thrombopoietin Receptor ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

Thrombopoietin confers immediate protection against injury caused by ischemia/reperfusion in the rat heart at a dose that does not increase platelet levels. Eltrombopag is a small molecule agonist of the thrombopoietin receptor; the physiological target of thrombopoietin. Administration of thrombopoietin and eltrombopag result in a dose- and time-dependent increase in platelet counts in patients with thrombocytopenia. However, the ability of eltrombopag and thrombopoietin to immediately protect human cardiac myocytes against injury and the mechanisms underlying myocyte protection are not known. Human cardiac myocytes (7500 cells, n=10/group) were treated with eltrombopag (0.1- 30.0 μM) or thrombopoietin ( 0.1 - 30.0 ng/ml) and then subjected to 5 hours of hypoxia (95% N 2 /5%CO 2 ) and 16 hours of reoxygenation to determine their ability to confer resistance to necrotic and apoptotic myocardial injury . The thrombopoietin receptor (c-Mpl) was detected in unstimulated human cardiac myocytes by western blotting. Eltrombopag and thrombopoietin confer immediate protection to human cardiac myocytes against injury from hypoxia/reoxygenation by decreasing necrotic and apoptotic cell death in a concentration-dependent manner with an optimal concentration of 3 μM for eltrombopag and 1.0 ng/ml for thrombopoietin. The extent of protection conferred to cardiac myocytes with eltrombopag is equivalent to that of thrombopoietin. Eltrombopag and thrombopoietin activate multiple pro-survival pathways; inhibition of JAK-2 (AG-490, 10 μM), p38 MAPK (SB203580, 10 μM), p44/42 MAPK (PD98059, 10 μM), Akt/PI 3 kinase (Wortmannin, 100 nM), and src kinase (PP1, 20 μM) prior to and during hypoxia abolished cardiac myocyte protection by eltrombopag and thrombopoietin. These inhibitors had no effect on hypoxia/reoxygenation injury in myocytes when used alone. Eltrombopag and thrombopoietin may represent important and potent agents for immediately and substantially increasing protection of human cardiac myocytes, and may offer long-lasting benefit through activation of pro-survival pathways during ischemia.

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