scholarly journals EGCG treats ICH via up-regulating miR-137-3p and inhibiting Parthanatos

2020 ◽  
Vol 11 (1) ◽  
pp. 371-379
Author(s):  
Jianjun Wang ◽  
Xuejun Kuang ◽  
Zhao Peng ◽  
Conghui Li ◽  
Chengwu Guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Functional Recovery ◽  
Essential Role ◽  
Therapeutic Agent ◽  
Mice Model ◽  
The Central Nervous System ◽  
Novel Strategy ◽  
Antioxidant Effects ◽  
Promising Therapeutic Agent

AbstractIntracranial hemorrhage (ICH) causes high mortality and disability without effective treatment in the clinical setting. (−)-Epigallocatechin-3-gallate (EGCG) exerts an essential role in the central nervous system and offers a promising therapeutic agent for the treatment of oxidative damage-related diseases. MiR-137 can inhibit the oxidative stress and apoptosis to attenuate neuronal injury. However, the role of EGCG in regulating miR-137-3p and neuronal Parthanatos remains to be unclear. In the present study, we build the ICH mice model to investigate the antioxidant effects of EGCG via upregulating miR-137-3p and inhibiting neuronal Parthanatos. We revealed that EGCG upregulated miR-137-3p and inhibited neuronal Parthanatos, and promoted the functional recovery, alleviated ICH-induced brain injury, and reduced oxidative stress in mice following ICH. However, following the inhibition of miR-137-3p and activation of Parthanatos, EGCG was unable to exert neuroprotective roles. These combined results suggest that EGCG may upregulate miR-137-3p and inhibit neuronal Parthanatos to accelerate functional recovery in mice after ICH, laying the foundation for EGCG to be a novel strategy for the treatment of neuronal injuries related to Parthanatos.

scholarly journals Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Jingya Gu ◽  
Chang Chen ◽  
Jue Wang ◽  
Tingting Chen ◽  
Wenjuan Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Withaferin A ◽  
Dependent Manner ◽  
Sirtuin 3 ◽  
Antifibrogenic Effect ◽  
Antioxidant Effects ◽  
Sirt3 Expression ◽  
Bioactive Constituent

Sirtuin 3 (SIRT3) is a deacetylase involved in the development of many inflammation-related diseases including liver fibrosis. Withaferin A (WFA) is a bioactive constituent derived from the Withania somnifera plant, which has extensive pharmacological activities; however, little is known about the regulatory role of SIRT3 in the WFA-induced antifibrogenic effect. The current study is aimed at investigating the role of SIRT3 in WFA-induced antioxidant effects in liver fibrosis. Our study verified that WFA attenuated platelet-derived growth factor BB- (PDGF-BB-) induced liver fibrosis and promoted PDGF-BB-induced SIRT3 activity and expression in JS1 cells. SIRT3 silencing attenuated the antifibrogenic and antioxidant effects of WFA in activated JS1 cells. Moreover, WFA inhibited carbon tetrachloride- (CCl4-) induced liver injury, collagen deposition, and fibrosis; increased the SIRT3 expression; and suppressed the CCl4-induced oxidative stress in fibrotic livers of C57/BL6 mice. Furthermore, the antifibrogenic and antioxidant effects of WFA could be available in CCl4-induced WT (129S1/SvImJ) mice but were unavailable in CCl4-induced SIRT3 knockout (KO) mice. Our study suggested that WFA inhibited liver fibrosis through the inhibition of oxidative stress in a SIRT3-dependent manner. WFA could be a potential compound for the treatment of liver fibrosis.

scholarly journals SIRT3 Is a Stress-Responsive Deacetylase in Cardiomyocytes That Protects Cells from Stress-Mediated Cell Death by Deacetylation of Ku70

2008 ◽  
Vol 28 (20) ◽  
pp. 6384-6401 ◽  
Author(s):  
Nagalingam R. Sundaresan ◽  
Sadhana A. Samant ◽  
Vinodkumar B. Pillai ◽  
Senthilkumar B. Rajamohan ◽  
Mahesh P. Gupta
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Gene Regulation ◽  
Essential Role ◽  
Short Form ◽  
Biological Functions ◽  
Proapoptotic Protein ◽  
Long Form ◽  
And Oxidative Stress

ABSTRACT There are seven SIRT isoforms in mammals, with diverse biological functions including gene regulation, metabolism, and apoptosis. Among them, SIRT3 is the only sirtuin whose increased expression has been shown to correlate with an extended life span in humans. In this study, we examined the role of SIRT3 in murine cardiomyocytes. We found that SIRT3 is a stress-responsive deacetylase and that its increased expression protects myocytes from genotoxic and oxidative stress-mediated cell death. We show that, like human SIRT3, mouse SIRT3 is expressed in two forms, a ∼44-kDa long form and a ∼28-kDa short form. Whereas the long form is localized in the mitochondria, nucleus, and cytoplasm, the short form is localized exclusively in the mitochondria of cardiomyocytes. During stress, SIRT3 levels are increased not only in mitochondria but also in the nuclei of cardiomyocytes. We also identified Ku70 as a new target of SIRT3. SIRT3 physically binds to Ku70 and deacetylates it, and this promotes interaction of Ku70 with the proapoptotic protein Bax. Thus, under stress conditions, increased expression of SIRT3 protects cardiomyocytes, in part by hindering the translocation of Bax to mitochondria. These studies underscore an essential role of SIRT3 in the survival of cardiomyocytes in stress situations.

scholarly journals Nanocurcumin Improves the Therapeutic Role of Mesenchymal Stem Cells in Liver Fibrosis Rats

2021 ◽  
Vol 11 (6) ◽  
pp. 14463-14479
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Therapeutic Agent ◽  
Albino Rats ◽  
Therapeutic Role ◽  
Recovery Group ◽  
Wistar Albino Rats ◽  
Promising Therapeutic Agent

Nano-curcumin (Nano-Cur) is a promising therapeutic agent that has a wide array of effective medicinal potentials. Therefore, the present inquiry aimed to assess Nano-Cur's impact on the therapeutic effect of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in the rat model of liver fibrosis prompted by carbon tetrachloride (CCl4). Liver fibrosis was developed in 30male Wistar albino rats which were divided into five groups, six animals each. The 1st group (CCl4 group) was sacrificed immediately after the induction of liver fibrosis. The 2nd group received a single iv injection of BM-MSCs and left for 4weeks, the3rd group received 100mg/kg b.w. Nano-Cur 3times/week for 4weeks, the 4th group received a single iv injection of 107 BM-MSCs accompanied with Nano-Cur 3times/week for 4weeks, and the 5th group left for 4weeks without any intervention. Data revealed that treatment with BM-MSCs plus Nano-Cur alleviated liver fibrosis through reducing liver oxidative stress and restoring both liver histological picture and enzymatic profile. Additionally, companied treatment resulted in reducing TGFβ1 levels and attenuating the expression of Smad 2,3 and collagen I, III genes. Conversely, most of the pathological lesions were still detected in the recovery group. Nano-Cur improves the therapeutic role of BM-MSCs in liver fibrosis rats.

scholarly journals Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila

2020 ◽  
Author(s):  
Qin Wang ◽  
Huaxun Fan ◽  
Feng Li ◽  
Savanna S. Skeeters ◽  
Vishnu Krishnamurthy ◽  
...  
Keyword(s):  
Nervous System ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Akt Signaling ◽  
Signaling Cascades ◽  
Neural Repair ◽  
Graded Response ◽  
The Central Nervous System ◽  
Novel Strategy ◽  
Multiple Signaling

AbstractNeuroregeneration is a dynamic process synergizing the functional outcomes of multiple signaling circuits. Channelrhodopsin-based optogenetics shows feasibility of stimulating neural repair but does not pin down specific signaling cascades. Here, we utilized optogenetic systems, optoRaf and optoAKT, to delineate the contribution of the ERK and AKT signaling pathways to neuroregeneration in live Drosophila larvae. We showed that optoRaf or optoAKT activation not only enhanced axon regeneration in both regeneration competent and incompetent sensory neurons in the peripheral nervous system, but also allowed temporal tuning and proper guidance of axon regrowth. Furthermore, optoRaf and optoAKT differ in their signaling kinetics during regeneration, showing a gated versus graded response, respectively. Importantly in the central nervous system, their activation promotes axon regrowth and functional recovery of the thermonociceptive behavior. We conclude that non-neuronal optogenetics target damaged neurons and signaling subcircuits, providing a novel strategy in the intervention of neural damage with improved precision.

scholarly journals Role of Polyphenols as Antioxidant Supplementation in Ischemic Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Yuan Zhou ◽  
Shanshan Zhang ◽  
Xiang Fan
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Cause Of Death ◽  
Experimental Studies ◽  
Reactive Oxygen Species Generation ◽  
Oxygen Species ◽  
Potential Therapeutic Target ◽  
Antioxidant Effects ◽  
And Oxidative Stress

Stroke is the second most common cause of death globally and the leading cause of death in China. The pathogenesis of cerebral ischemia injury is complex, and oxidative stress plays an important role in the fundamental pathologic progression of cerebral damage in ischemic stroke. Previous studies have preliminarily confirmed that oxidative stress should be a potential therapeutic target and antioxidant as a treatment strategy for ischemic stroke. Emerging experimental studies have demonstrated that polyphenols exert the antioxidant potential to play the neuroprotection role after ischemic stroke. This comprehensive review summarizes antioxidant effects of some polyphenols, which have the most inhibition effects on reactive oxygen species generation and oxidative stress after ischemic stroke.

scholarly journals Amelioratory Effect of Nanoconjugated Vancomycin on Spleen during VRSA-Induced Oxidative Stress

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Subhankari Prasad Chakraborty ◽  
Santanu KarMahapatra ◽  
Sumanta Kumar Sahu ◽  
Panchanan Pramanik ◽  
Somenath Roy
Keyword(s):  
Oxidative Stress ◽  
Reduced Glutathione ◽  
Treated Group ◽  
Control Group ◽  
Myeloperoxidase Activity ◽  
Viable Bacteria ◽  
Antioxidant Effects ◽  
Potential Use

Objective. The aim of the present study was to evaluate the possible antioxidant effects of nanoconjugated vancomycin against VRSA infection on select makers of oxidative damage and antioxidant status in spleen. Methods. A coagulase-positive VRSA strain was used for this study. VRSA infection was developed in Swiss mice by intraperitoneal injection of 5 × 106 CFU/mL bacterial solutions. VRSA-infected mice were treated with nanoconjugated vancomycin at its effective dose for 10 days. After decapitation, blood was used for determination of viable bacteria count and spleen was excised from control and experimental groups, homogenized and used for different biochemical estimations. Results. Nitrate level, myeloperoxidase activity, lipid peroxidation, protein oxidation, oxidized glutathione, and DNA fragmentation level were increased significantly (P<0.05) in spleen of VRSA-infected group as compared to control group, and reduced glutathione level, activity of SOD, CAT, GPx, GR, and GST were decreased significantly (P<0.05); which were increased or decreased significantly (P<0.05) near to normal in nanoconjugated vancomycin-treated group. Conclusion. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin against VRSA-infection-induced oxidative stress and DNA damage in spleen.

scholarly journals Potential Role of Phenolic Extracts of Mentha in Managing Oxidative Stress and Alzheimer’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 631
Author(s):  
Doaa M. Hanafy ◽  
Geoffrey E. Burrows ◽  
Paul D. Prenzler ◽  
Rodney A. Hill
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Role ◽  
The Elderly ◽  
Future Research ◽  
Phenolic Constituents ◽  
The Central Nervous System ◽  
Developed Nations

With an increase in the longevity and thus the proportion of the elderly, especially in developed nations, there is a rise in pathological conditions that accompany ageing, such as neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory decline. The pathophysiology of the disease is poorly understood, with several factors contributing to its development, such as oxidative stress, neuroinflammation, cholinergic neuronal apoptotic death, and the accumulation of abnormal proteins in the brain. Current medications are only palliative and cannot stop or reverse the progression of the disease. Recent clinical trials of synthetic compounds for the treatment of AD have failed because of their adverse effects or lack of efficacy. Thus, there is impetus behind the search for drugs from natural origins, in addition to the discovery of novel, conventional therapeutics. Mints have been used traditionally for conditions relevant to the central nervous system. Recent studies showed that mint extracts and/or their phenolic constituents have a neuroprotective potential and can target multiple events of AD. In this review, we provide evidence of the potential role of mint extracts and their derivatives as possible sources of treatments in managing AD. Some of the molecular pathways implicated in the development of AD are reviewed, with focus on apoptosis and some redox pathways, pointing to mechanisms that may be modulated for the treatment of AD, and the need for future research invoking knowledge of these pathways is highlighted.

Role of Kinaesthesia in Arousal and Learning Behavior

1978 ◽  
Vol 47 (3_suppl) ◽  
pp. 1219-1225 ◽  
Author(s):  
L. Swartz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Learning Disabilities ◽  
Adaptive Behavior ◽  
Essential Role ◽  
Learning Behavior ◽  
The Central Nervous System ◽  
Bizarre Behavior

This article presents a rationale of the significance of kinaesthesia. The development of arousal in the central nervous system is primarily peripheral and based on kinaesthesia. Consistent adaptive behavior results from adequate kinaesthetic perception and is the foundation for intersensory integration. Without kinaesthesia learning develops unevenly, as in children with learning disabilities. Inconsistent, bizarre behavior evident in psychopathology may result from inadequate, distorted kinaesthetic perception. Visual and auditory perceptual processes have been researched but the essential role of kinaesthetic perception has been neglected. The implications of adequate kinaesthesia are relevant to teaching and to psychotherapy.

scholarly journals A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xi Shuhua ◽  
Liu Ziyou ◽  
Yan Ling ◽  
Wang Fei ◽  
Guifan Sun
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Dependent Manner ◽  
Microglia Cell ◽  
The Central Nervous System ◽  
Radical Generation ◽  
Oxide Synthase ◽  
Cell Medium ◽  
Dose Dependent

The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide anions (O2∙-), nitric oxide synthase (NOS), nitrotyrosine (NT) and nitric oxide (NO), NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20 mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS andO2∙-increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50 mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species.

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