scholarly journals Up-regulated microRNA-185-3p inhibits the development of hyperlipidemia in rats

2021 ◽  
Author(s):  
Hua Zhao ◽  
yanbing Li
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Lipid Accumulation ◽  
Adenoviral Vectors ◽  
Cellular Morphology ◽  
Inflammatory Factors ◽  
Multiple Cancers ◽  
Biochemical Indices ◽  
Novel Therapeutic ◽  
Liver Tissues

Abstract Objective MicroRNA (miR)-185-3p roles have been probed in multiple cancers, while the underlying function of miR-185-3p in hyperlipidemia remained obscure. This research was conducted to unravel miR-185-3p function in hyperlipidemia development via modulating mastermind-like 1 (MAML1). Methods The hyperlipidemia rat model was constructed. MiR-185-3p and MAML1 levels in hyperlipidemia rats were detected. Adenoviral vectors altering miR-185-3p and MAML1 levels were injected into hyperlipidemia rats to examine the levels of biochemical indices, inflammatory factors, oxidative stress, lipid accumulation and cellular morphology in liver tissues of hyperlipidemia rats. The targeting relation between miR-185-3p and MAML1 was manifested. Results MiR-185-3p levels were depleted while MAML1 expression was elevated in HH rats. MiR-185-3p overexpression or MAML1 silencing reduced levels of inflammatory factors in serum, mitigated oxidative stress and biochemical response, relieved lipid accumulation and cellular morphology in liver tissues; while up-regulated MAML1 reversed the effects of augmented MAML1 in hyperlipidemia rats. MiR-185-3p targeted MAML1. Conclusion Up-regulated miR-185-3p represses hyperlipidemia development via modulating MAML1. This research provides novel therapeutic candidates for the treatment of hyperlipidemia.

scholarly journals Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Li ◽  
Zhimin Dou ◽  
Lei Zhang ◽  
Lei Zhu ◽  
Yongqiang Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Interleukin 1 ◽  
Cecal Ligation ◽  
Intestinal Barrier ◽  
Matrix Metalloproteinase 2 ◽  
Inflammatory Factors ◽  
Loss Of Function ◽  
Barrier Dysfunction

Intestinal barrier dysfunction is an important contributor to morbidity caused by sepsis. This study investigates the molecular mechanism by which Ghrelin affects intestinal dysfunction in rat model of sepsis. A rat model of sepsis was established by cecal ligation and puncture (CLP), revealing that Ghrelin was downregulated when sepsis occurs. Increases in the levels of inflammatory factors tumor necrosis factor α (TNF-α), interleukin-1 (IL-1β), IL-6, gastrin, γ-H2AX and 8-OHdG was also detected in this model system, as was an overall increase in oxidative stress. Introduction of exogenous Ghrelin inhibited these increases in inflammatory response and oxidative stress, leading to a reduction of overall sepsis-induced intestinal dysfunction. Ghrelin was then shown to activate SIRT1 expression in vitro, while SIRT1 was found to co-express with KLF4, which in turn was predicted to bind to matrix metalloproteinase 2 (MMP2) promoter. Finally, gain- and loss-of-function experiment demonstrated that SIRT1 upregulated the expression of KLF4 to downregulate MMP2. Collectively, Ghrelin inhibits the oxidative stress and intestinal dysfunction to attenuate sepsis by activating SIRT1 and regulating a KLF4/MMP2 regulatory axis.

scholarly journals Network Pharmacology and Molecular Docking Verify the Mechanism of Qinshi Simiao San in Treating Chronic Prostatitis in the Rat Model

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Chenxi Li ◽  
Lei Xu ◽  
Xuyao Lin ◽  
Qingrui Li ◽  
Shaoming Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Molecular Mechanism ◽  
Rat Model ◽  
Chronic Prostatitis ◽  
Target Genes ◽  
Reduction Process ◽  
Inflammatory Factors ◽  
Network Pharmacology ◽  
Network Graph

Background. Using network pharmacology and molecular docking, this study aimed to explore the active pharmaceutical ingredients (APIs) and molecular mechanism of Qinshi Simiao San (QSSMS) in the treatment of chronic prostatitis (CP) and verify our findings in the rat model. Methods. The APIs of QSSMS and the common targets of QSSMS and CP were screened from the TCMSP database. The STRING database and Cytoscape software were used to construct the network graph. The enriched GO and KEGG pathways were displayed by David software and R software. Molecular docking was performed to visualize key components and target genes. In addition, the rats model of CP was established to verify the molecular mechanism of QSSMS. Results. Network pharmacology showed that the APIs of QSSMS mainly included quercetin, kaempferol, formononetin, isorhamnetin, and calycosin. QSSMS alleviated CP mainly through the negative regulation of the apoptotic process, oxidation-reduction process, inflammatory response, and immune response. Molecular docking showed that the APIs could bind to the corresponding targets. QSSMS repaired the pathological damage of prostate tissue, upregulated the expression of oxidative stress scavenging enzymes CAT and SOD, and downregulated the peroxidative product MDA, inflammatory factors IL-1β, IL-6, TNF-α, COX-2, PGE2, and NGF, and immune factors IgG and SIgA. Conclusion. The APIs in QSSMS may inhibit inflammation in the rat CP model by regulating immune and oxidative stress.

scholarly journals Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4627
Author(s):  
Richard Jayaraj ◽  
Rami Beiram ◽  
Sheikh Azimullah ◽  
Nagoor M. F. ◽  
Shreesh Ojha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Substantia Nigra ◽  
Rat Model ◽  
Dopaminergic Neurons ◽  
Dopaminergic Neuron ◽  
Substantia Nigra Pars Compacta ◽  
Inflammatory Factors ◽  
Lysosomal Degradation ◽  
Dopaminergic Neuron Loss

Parkinson’s disease is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and the resultant loss of dopamine in the striatum. Various studies have shown that oxidative stress and neuroinflammation plays a major role in PD progression. In addition, the autophagy lysosome pathway (ALP) plays an important role in the degradation of aggregated proteins, abnormal cytoplasmic organelles and proteins for intracellular homeostasis. Dysfunction of ALP results in the accumulation of α-synuclein and the loss of dopaminergic neurons in PD. Thus, modulating ALP is becoming an appealing therapeutic intervention. In our current study, we wanted to evaluate the neuroprotective potency of noscapine in a rotenone-induced PD rat model. Rats were administered rotenone injections (2.5 mg/kg, i.p.,) daily followed by noscapine (10 mg/kg, i.p.,) for four weeks. Noscapine, an iso-qinulinin alkaloid found naturally in the Papaveraceae family, has traditionally been used in the treatment of cancer, stroke and fibrosis. However, the neuroprotective potency of noscapine has not been analyzed. Our study showed that administration of noscapine decreased the upregulation of pro-inflammatory factors, oxidative stress, and α-synuclein expression with a significant increase in antioxidant enzymes. In addition, noscapine prevented rotenone-induced activation of microglia and astrocytes. These neuroprotective mechanisms resulted in a decrease in dopaminergic neuron loss in SNpc and neuronal fibers in the striatum. Further, noscapine administration enhanced the mTOR-mediated p70S6K pathway as well as inhibited apoptosis. In addition to these mechanisms, noscapine prevented a rotenone-mediated increase in lysosomal degradation, resulting in a decrease in α-synuclein aggregation. However, further studies are needed to further develop noscapine as a potential therapeutic candidate for PD treatment.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

Oxidative Stress and Pathophysiology of Ischemic Stroke: Novel Therapeutic Opportunities

2013 ◽  
Vol 12 (5) ◽  
pp. 698-714 ◽  
Author(s):  
Ramon Rodrigo ◽  
Rodrigo Fernandez-Gajardo ◽  
Rodrigo Gutierrez ◽  
Jose Matamala ◽  
Rodrigo Carrasco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Novel Therapeutic

The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 578-586
Author(s):  
Areeg M. Abdelrazek ◽  
Shimaa A. Haredy
Keyword(s):  
Oxidative Stress ◽  
Coenzyme Q10 ◽  
Protective Role ◽  
Albino Rats ◽  
Distilled Water ◽  
Negative Effects ◽  
Adult Rats ◽  
Stress Damage ◽  
The Impact ◽  
Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD

2021 ◽  
Author(s):  
Jingda Li ◽  
Tianqi Wang ◽  
Panpan Liu ◽  
Fuyuan Yang ◽  
Xudong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oleic Acid ◽  
Rat Model ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Citrus Fruits ◽  
High Fat ◽  
Hepatic Oxidative Stress

Hesperetin as a major bioflavonoid in citrus fruits improves NAFLD by suppressing hepatic oxidative stress and inflammation.

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