scholarly journals Emodin Prevented Depression in Chronic Unpredicted Mild Stress Exposured Rats by Targeting miR139-5p/5-Lipoxygenase

2020 ◽  
Author(s):  
Teng Zhang ◽  
Can Yang ◽  
Jiang Chu ◽  
Linna Ning ◽  
Peng Zeng ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Glycogen Synthase ◽  
Young Male ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Related Factor ◽  
Mild Stress ◽  
Proteomics Analysis ◽  
Vehicle Treatment

Abstract Background: Compelling evidences have highlighted the role of inflammation as a possible mechanism linking stress to depression. Anti-inflammatory treatment might block the occurrence of stress-induced depression. Emodin, a natural active compound extracted from rhubarb, has the biological activity of anti-inflammation. Here, the effect of emodin on the depressed young male rats and the underlying mechanism were studied. Methods: The proteomics analysis of hippocampi, which were taken from depression (Dep) rats, depression resistant (Res) rats and control (Ctrl) rats after 7 weeks’ chronic unpredicted mild stress (CUMS), were performed. We also screened out depression susceptible (DeS) rats and stress insensitive (Ins) rats at the end of 5th week in CUMS. While exposed to CUMS, DeS rats received daily emodin (Emo, 80mg/kg) or vehicle treatment (Veh) for 2 weeks.Results: Inflammation was suggested by the proteomics analysis of hippocampi taken from Dep rats, Res rats and Ctrl rats. Emodin obviously improved the depression behaviors and a series of pathological changes in hippocampus, such as hippocampal neuron and spine loss, microglia activation, increased interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a), and the activation of 5-lipoxygenase (5-LO). Furtherly, we demonstrated that emodin inhibited its excess inflammatory responses possibly by targeting miR139-5p/5-LO and modulating the downstream glycogen synthase kinase 3β (GSK3β) and nuclear factor erythroid 2-related factor 2 (Nrf2). Conclusions: These results established a key role of miR139-5p/5-LO in the development of depression and provided an important evidence that emodin may be a candidate agent for the treatment of depression.

scholarly journals Emodin Prevented Depression in Chronic Unpredicted Mild Stress Exposured Rats by Targeting MiR139-5p/5-Lipoxygenase

2021 ◽  
Author(s):  
Teng Zhang ◽  
Can Yang ◽  
Jiang Chu ◽  
Linna Ning ◽  
Peng Zeng ◽  
...  
Keyword(s):  
Psychosocial Stress ◽  
Inflammatory Responses ◽  
Glycogen Synthase ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Mild Stress ◽  
Nissl Staining ◽  
Force Swimming Test ◽  
Sucrose Preference Test

Abstract Background: Using ingredients of medicinal plants is one of the goals of developing potential drugs for treating depression. Compelling evidences suggested anti-inflammation might block the occurrence of depression. Here, the effect of a natural compound, emodin, on the developing of psychosocial stress-induced depression and the underlying mechanism were studied.Methods: 7 weeks’ chronic unpredicted mild stress (CUMS) were performed to replicate psychosocial stress in rats, and sucrose preference test, force swimming test and open field test were used to evaluate their behaviors. The differentially expressed proteins in hippocampus were analyzed by proteomics. Nissl staining and Golgi staining were used to detect the losses of neurons and synapses, immunohistochemical staining was used to detect the activation of microglia, and ELISA was used to detect the levels of pro-inflammatory cytokines. Western blotting, immunofluorescence and quantitative PCR were also included.Results: Hippocampal inflammation with up-regulated 5-lipoxygenase (5-LO) was observed in the depressed rats after CUMS exposure. And the up-regulation of 5-LO was proved to be caused by the decrease of miR139-5p. To observe the effect of emodin, we screened out depression susceptible (DeS) rats during CUMS and treated them with emodin (80mg/kg/day). 2 weeks later, emodin obviously prevented the depression behaviors of DeS rats and a series of pathological changes in their hippocampi, such as losses of neurons and spines, microglia activation, increased interleukin-1b and tumor necrosis factor-a, and the activation of 5-LO. Furtherly, we demonstrated that emodin inhibited its excess inflammatory responses possibly by targeting miR139-5p/5-LO and modulating the downstream glycogen synthase kinase 3β and nuclear factor erythroid 2-related factor 2. Conclusions: These results provided an important evidence that emodin may be a candidate agent for the treatment of depression and established a key role of miR139-5p/5-LO in the inflammation of depression.

scholarly journals Involvement of NRF2 in Breast Cancer and Possible Therapeutical Role of Polyphenols and Melatonin

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1853
Author(s):  
Alev Tascioglu Aliyev ◽  
Emiliano Panieri ◽  
Višnja Stepanić ◽  
Hande Gurer-Orhan ◽  
Luciano Saso
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Loss Of Control ◽  
Breast Cancer Therapy ◽  
Cancer Breast ◽  
Prevention And Treatment

Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of the former and a loss of control over redox signaling processes, leading to potential biomolecular damage. It is involved in the etiology of many diseases, varying from diabetes to neurodegenerative diseases and cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor and reported as one of the most important oxidative stress regulators. Due to its regulatory role in the expression of numerous cytoprotective genes involved in the antioxidant and anti-inflammatory responses, the modulation of NRF2 seems to be a promising approach in the prevention and treatment of cancer. Breast cancer is the prevalent type of tumor in women and is the leading cause of death among female cancers. Oxidative stress-related mechanisms are known to be involved in breast cancer, and therefore, NRF2 is considered to be beneficial in its prevention. However, its overactivation may lead to a negative clinical impact on breast cancer therapy by causing chemoresistance. Some known “oxidative stress modulators”, such as melatonin and polyphenols, are suggested to play an important role in the prevention and treatment of cancer, where the activation of NRF2 is reported as a possible underlying mechanism. In the present review, the potential involvement of oxidative stress and NRF2 in breast cancer will be reviewed, and the role of the NRF2 modulators—namely, polyphenols and melatonin—in the treatment of breast cancer will be discussed.

scholarly journals Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

2021 ◽  
Vol 22 (12) ◽  
pp. 6197
Author(s):  
Paola Brivio ◽  
Giulia Sbrini ◽  
Letizia Tarantini ◽  
Chiara Parravicini ◽  
Piotr Gruca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Male Rats ◽  
Mild Stress ◽  
Experimental Conditions ◽  
Glucocorticoid Responsive Element ◽  
Responsive Element

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

scholarly journals Injured liver-released miRNA-122 elicits acute pulmonary inflammation via activating alveolar macrophage TLR7 signaling pathway

2019 ◽  
Vol 116 (13) ◽  
pp. 6162-6171 ◽  
Author(s):  
Yanbo Wang ◽  
Hongwei Liang ◽  
Fangfang Jin ◽  
Xin Yan ◽  
Guifang Xu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alveolar Macrophage ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Underlying Mechanism ◽  
Causative Role ◽  
Independent Manner ◽  
Liver Injuries

Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underlying mechanism is not fully elucidated. Here we identify hepatic miR-122 as a mediator of pulmonary inflammation induced by various liver injuries. Analyses of acute and chronic liver injury mouse models confirm that liver dysfunction can cause pulmonary inflammation and tissue damage. Injured livers release large amounts of miR-122 in an exosome-independent manner into the circulation compared with normal livers. Circulating miR-122 is then preferentially transported to mouse lungs and taken up by alveolar macrophages, in which it binds Toll-like receptor 7 (TLR7) and activates inflammatory responses. Depleting miR-122 in mouse liver or plasma largely abolishes liver injury-induced pulmonary inflammation and tissue damage. Furthermore, alveolar macrophage activation by miR-122 is blocked by mutating the TLR7-binding GU-rich sequence on miR-122 or knocking out macrophage TLR7. Our findings reveal a causative role of hepatic miR-122 in liver injury-induced pulmonary dysfunction.

scholarly journals miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianlei Zhang ◽  
Wei Liu ◽  
Yabo Wang ◽  
Shengnan Zhao ◽  
Na Chang
Keyword(s):  
Cell Proliferation ◽  
Glycogen Synthase ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Inflammatory Cytokine Production ◽  
Protein Levels

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.

scholarly journals Emodin Prevented Depression in Chronic Unpredicted Mild Stress-Exposed Rats by Targeting miR-139-5p/5-Lipoxygenase

2021 ◽  
Vol 9 ◽  
Author(s):  
Teng Zhang ◽  
Can Yang ◽  
Jiang Chu ◽  
Lin-Na Ning ◽  
Peng Zeng ◽  
...  
Keyword(s):  
Psychosocial Stress ◽  
Glycogen Synthase ◽  
Quantitative Polymerase Chain Reaction ◽  
Preference Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Related Factor ◽  
Mild Stress ◽  
Nissl Staining ◽  
Force Swimming Test ◽  
Underlying Mechanisms

BackgroundThe use of medicinal plant ingredients is one of the goals of developing potential drugs for treating depression. Compelling evidence suggests that anti-inflammatory medicines may block the occurrence of depression. We studied the effect of a natural compound, emodin, on the development of psychosocial stress-induced depression and the underlying mechanisms.MethodsChronic unpredicted mild stress (CUMS) for 7 weeks was performed to replicate psychosocial stress in rats. The sucrose preference test, force swimming test, and open field test were used to evaluate their behaviors. The differentially expressed proteins in the hippocampus were analyzed using proteomics. Nissl staining and Golgi staining were used to detect the loss of neurons and synapses, immunohistochemical staining was used to detect the activation of microglia, and the enzyme-linked immunosorbent assay was used to detect the levels of pro-inflammatory cytokines. Western blotting, immunofluorescence, and quantitative polymerase chain reaction were also performed.ResultsHippocampal inflammation with up-regulated 5-lipoxygenase (5-LO) was observed in the depressed rats after CUMS exposure. The upregulation of 5-LO was caused by decreased miR-139-5p. To observe the effect of emodin, we screened out depression-susceptible (DeS) rats during CUMS and treated them with emodin (80 mg/kg/day). Two weeks later, emodin prevented the depression behaviors in DeS rats along with a series of pathological changes in their hippocampi, such as loss of neurons and spines, microglial activation, increased interleukin-1β and tumor necrosis factor-α, and the activation of 5-LO. Furthermore, we demonstrated that emodin inhibited its excess inflammatory response, possibly by targeting miR-139-5p/5-LO and modulating glycogen synthase kinase 3β and nuclear factor erythroid 2-related factor 2.ConclusionThese results provide important evidence that emodin may be a candidate agent for the treatment of depression and established a key role of miR-139-5p/5-LO in the inflammation of depression.

scholarly journals The Role of the Nrf2 Signaling in Obesity and Insulin Resistance

2020 ◽  
Vol 21 (18) ◽  
pp. 6973 ◽  
Author(s):  
Shiri Li ◽  
Natsuki Eguchi ◽  
Hien Lau ◽  
Hirohito Ichii
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Leucine Zipper ◽  
Close Association ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Basic Leucine Zipper ◽  
State Of Research ◽  
And Oxidative Stress

Obesity, a metabolic disorder characterized by excessive accumulation of adipose tissue, has globally become an increasingly prevalent disease. Extensive studies have been conducted to elucidate the underlying mechanism of the development of obesity. In particular, the close association of inflammation and oxidative stress with obesity has become increasingly evident. Obesity has been shown to exhibit augmented levels of circulating proinflammatory cytokines, which have been associated with the activation of pathways linked with inflammation-induced insulin resistance, a major pathological component of obesity and several other metabolic disorders. Oxidative stress, in addition to its role in stimulating adipose differentiation, which directly triggers obesity, is considered to feed into this pathway, further aggravating insulin resistance. Nuclear factor E2 related factor 2 (Nrf2) is a basic leucine zipper transcription factor that is activated in response to inflammation and oxidative stress, and responds by increasing antioxidant transcription levels. Therefore, Nrf2 has emerged as a critical new target for combating insulin resistance and subsequently, obesity. However, the effects of Nrf2 on insulin resistance and obesity are controversial. This review focuses on the current state of research on the interplay of inflammation and oxidative stress in obesity, the role of the Nrf2 pathway in obesity and insulin resistance, and the potential use of Nrf2 activators for the treatment of insulin resistance.

scholarly journals Rutaecarpine Inhibits Doxorubicin-Induced Oxidative Stress and Apoptosis by Activating AKT Signaling Pathway

2022 ◽  
Vol 8 ◽  
Author(s):  
Zi-Qi Liao ◽  
Yi-Nong Jiang ◽  
Zhuo-Lin Su ◽  
Hai-Lian Bi ◽  
Jia-Tian Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Fibrosis ◽  
Heart Function ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Pcr Analysis ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Akt Inhibitor

Patients with cancer who receive doxorubicin (DOX) treatment can experience cardiac dysfunction, which can finally develop into heart failure. Oxidative stress is considered the most important mechanism for DOX-mediated cardiotoxicity. Rutaecarpine (Rut), a quinazolinocarboline alkaloid extracted from Evodia rutaecarpa was shown to have a protective effect on cardiac disease. The purpose of this study is to investigate the role of Rut in DOX-induced cardiotoxicity and explore the underlying mechanism. Intravenous injection of DOX (5 mg/kg, once a week) in mice for 4 weeks was used to establish the cardiotoxic model. Echocardiography and pathological staining analysis were used to detect the changes in structure and function in the heart. Western blot and real-time PCR analysis were used to detect the molecular changes. In this study, we found that DOX time-dependently decreased cardiac function with few systemic side effects. Rut inhibited DOX-induced cardiac fibrosis, reduction in heart size, and decrease in heart function. DOX-induced reduction in superoxide dismutase (SOD) and glutathione (GSH), enhancement of malondialdehyde (MDA) was inhibited by Rut administration. Meanwhile, Rut inhibited DOX-induced apoptosis in the heart. Importantly, we further found that Rut activated AKT or nuclear factor erythroid 2-related factor 2 (Nrf-2) which further upregulated the antioxidant enzymes such as heme oxygenase-1 (HO-1) and GSH cysteine ligase modulatory subunit (GCLM) expression. AKT inhibitor (AKTi) partially inhibited Nrf-2, HO-1, and GCLM expression and abolished the protective role of Rut in DOX-induced cardiotoxicity. In conclusion, this study identified Rut as a potential therapeutic agent for treating DOX-induced cardiotoxicity by activating AKT.

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