scholarly journals Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 82
Author(s):  
Soudeh Ghafouri-Fard ◽  
Hamed Shoorei ◽  
Zahra Bahroudi ◽  
Bashdar Mahmud Hussen ◽  
Seyedeh Fahimeh Talebi ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Diseases ◽  
Therapeutic Effects ◽  
Pathological Conditions ◽  
Anti Cancer ◽  
Natural Polyphenol ◽  
Response To Stress ◽  
Therapeutic Substance ◽  
Anti Inflammation

Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

scholarly journals The Role of 5-Lipoxygenase and Leukotrienes in Shock and Ischemia-Reperfusion Injury

2007 ◽  
Vol 7 ◽  
pp. 56-74 ◽  
Author(s):  
Antonietta Rossi ◽  
Carlo Pergola ◽  
Salvatore Cuzzocrea ◽  
Lidia Sautebin
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Biological Activities ◽  
Ischemia Reperfusion ◽  
Targeted Disruption ◽  
Pathological Conditions ◽  
Metabolic Products ◽  
Important Regulator ◽  
Multicellular Organisms

The leukotrienes (LTs) are metabolic products of arachidonic acid via the 5-lipoxygenase (5-LO) pathway. The biological activities of LTs suggest that they are mediators of acute inflammatory and immediate hypersensitivity responses. In particular, the 5-LO activation has been proposed to be an important regulator for pathogenesis in multicellular organisms. The role of LTs in tissue damage, associated with septic and nonseptic shock and ischemia-reperfusion, has been extensively studied by the use of 5-LO inhibitors, receptor antagonists, and mice with a targeted disruption of the 5-LO gene (5-LOKO). In particular, several data indicate that LTs regulate neutrophil trafficking in damaged tissue in shock and ischemia-reperfusion, mainly through the modulation of adhesion molecule expression. This concept may provide new insights into the interpretation of the protective effect of 5-LO inhibition, which may be useful in the therapy of pathological conditions associated with septic and nonseptic shock and ischemia-reperfusion injury.

scholarly journals Histone Hyperacetylation as a Response to Global Brain Ischemia Associated with Hyperhomocysteinemia in Rats

2018 ◽  
Vol 19 (10) ◽  
pp. 3147 ◽  
Author(s):  
Barbara Tóthová ◽  
Mária Kovalská ◽  
Dagmar Kalenská ◽  
Anna Tomašcová ◽  
Ján Lehotský
Keyword(s):  
Histone Acetylation ◽  
Primary Motor Cortex ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cresyl Violet ◽  
Cortical Region ◽  
Global Brain Ischemia ◽  
Endogenous Factors ◽  
Pathological Conditions ◽  
Cornu Ammonis

Epigenetic regulations play an important role in both normal and pathological conditions of an organism, and are influenced by various exogenous and endogenous factors. Hyperhomocysteinemia (hHcy), as a risk factor for several pathological conditions affecting the central nervous system, is supposed to alter the epigenetic signature of the given tissue, which therefore worsens the subsequent damage. To investigate the effect of hHcy in combination with ischemia-reperfusion injury (IRI) and histone acetylation, we used the hHcy animal model of global forebrain ischemia in rats. Cresyl violet staining showed massive neural disintegration in the M1 (primary motor cortex) region as well as in the CA1 (cornu ammonis 1) area of the hippocampus induced by IRI. Neural loss was significantly higher in the group with induced hHcy. Moreover, immunohistochemistry and Western blot analysis of the brain cortex showed prominent changes in the acetylation of histones H3 and H4, at lysine 9 and 12, respectively, as a result of IRI and induced hHcy. It seems that the differences in histone acetylation patterns in the cortical region have a preferred role in pathological processes induced by IRI associated with hHcy and could be considered in therapeutic strategies.

scholarly journals Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2884 ◽  
Author(s):  
Eun-Jung In ◽  
Yuno Lee ◽  
Sushruta Koppula ◽  
Tae-Yeon Kim ◽  
Jun-Hyuk Han ◽  
...  
Keyword(s):  
Cell Death ◽  
Md Simulation ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Therapeutic Implications ◽  
Pathological Conditions ◽  
Tnf Α

Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis factor-α (TNF-α) and toll-like receptor (TLR) agonists. Mechanistic studies revealed that NTB451 inhibited phosphorylation and oligomerization of mixed lineage kinase domain like (MLKL), and this activity was linked to its inhibitory effect on the formation of the receptor interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3 complex. Small interfering RNA (siRNA)-mediated RIPK1 knockdown, drug affinity responsive target stability assay, and molecular dynamics (MD) simulation study illustrated that RIPK1 is a specific target of NTB451. Moreover, MD simulation showed a direct interaction of NTB451 and RIPK1. Further experiments to ensure that the inhibitory effect of NTB451 was restricted to necroptosis and NTB451 had no effect on nuclear factor-κB (NF-κB) activation or apoptotic cell death upon triggering with TNF-α were also performed. Considering the data obtained, our study confirmed the potential of NTB451 as a new necroptosis inhibitor, suggesting its therapeutic implications for pathological conditions induced by necroptotic cell death.

scholarly journals The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Mingxuan Chi ◽  
Kuai Ma ◽  
Jing Wang ◽  
Zhaolun Ding ◽  
Yunlong Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Renal Diseases

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

scholarly journals Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Ningwei Che ◽  
Tingting Zhou ◽  
Xiangwen Zhang
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Ginsenoside Rg1 ◽  
Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

Abstract WP108: Co-transplantation of NPCs and EPCs Synergistically Promotes Brain Recovery After Ischemia-reperfusion Injury in Mice

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jinju Wang ◽  
Xiaotang Ma ◽  
Shuzhen Chen ◽  
Xiang Xiao ◽  
Ji Bihl ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Motor Function ◽  
Ischemia Reperfusion Injury ◽  
Synergistic Effects ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Gene Expressions ◽  
Protein Ratio ◽  
Infarct Area

Introduction: The promising of neuron progenitor cells (NPCs) or endothelial progenitor cells (EPCs) for treating ischemic stroke has been recognized. In this study, we determined the therapeutic effects of NPC and EPC co-transplantation and the underlying mechanisms in a mouse model of ischemia-reperfusion (I-R) stroke. Methods: NPCs and EPCs were generated from human inducible pluripotent stem cells. C57BL/6 adult mice were subjected to middle cerebral artery occlusion (MCAO; 90 min) followed by reperfusion (30 min), and treated with (n=10/group): 1) PBS; 2) EPCs; 3) NPCs; 4) EPCs+NPCs (1:1 ratio); 5) EPCs+NPCs (1:1 ratio)+LY294002 (1μM). Cells (3x105/2μl PBS) were injected into ipsilateral striatum at 2 sites (1μl/site). Bromodeoxyuridine (BrdU, 65 mg/g/day, i.p.) was injected to label the new generated cells. Mice were sacrificed at days 2 and 10. Motor function (Rotarod test and neurologic deficit score), infarct volume, cerebral microvascular density (cMVD), neurogenesis and angiogenesis, and gene expressions of the PI3K/Akt pathway were evaluated. Results: Co-transplantation of EPCs and NPCs exhibited synergistic effects on improving motor function, increasing cMVD in the peri-infarct area, and decreasing infarct volume at days 2 and 10 (refer to table). Moreover, neurogenesis (Brdu+NeuN+) and angiogenesis (Brdu+CD31+) in the peri-infarct area were largely enhanced in the co-transplantation group at day 10 (refer to table). In addition, the protein ratio of p-Akt/Akt was increased in the brain in the co-transplantation group (p<0.05). These effects were significantly reduced by LY294002 administration. Conclusion: Co-transplantation of NPCs and EPCs synergistically increases cMVD, promotes angiogenesis and neurogenesis, and improves functional outcome in I-R injured mice. Activation of the PI3K/Akt signal pathway contributes to the synergistic effects of NPCs and EPCs.

scholarly journals STUDY ON THE SYNTHESIS OF PUERARIN DERIVATIVES AND THEIR ANTI-VASCULAR DEMENTIA ACTIVITY

2016 ◽  
Vol 8 (2) ◽  
pp. 11
Author(s):  
Pei Jiang
Keyword(s):  
Vascular Dementia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cyclooxygenase 2 ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
H Nmr ◽  
Cox 2 ◽  
Oxide Synthase

<p class="lead">In this study, puerarin derivatives were designed by adding an active acetonitrile group that inhibits cyclooxygenase-2 (COX-2) in order to enhance the anti-vascular dementia drug activity. The acetonitrile group was linked to puerarin at the 7/4 'positions by a phenolic hydroxyl to give 7-mono-and 7, 4' di-substituted derivatives of puerarin. These structures were confirmed by <sup>1</sup>H NMR spectroscopy and MS spectroscopy. We compared the affinity of puerarin derivatives and puerarin for cyclooxygenase-2 (COX-2) using molecular docking. In addition, the anti-vascular dementia activity of the developed puerarin derivatives was studied by water maze, novel object recognition, and the determination of inducible nitric oxide synthase (iNOS) enzyme activity at the cerebral cortex of mice. Experimental results showed that the puerarin derivatives have a good affinity for COX-2 with therapeutic effects against vascular dementia. The results of this study suggest that the protective effects of the puerarin derivatives against vascular dementia may be related to suppression of inflammation associated with ischemia-reperfusion injury through inhibition of COX-2.</p>

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