scholarly journals Protective Effects of 6-(Methylsulfinyl)hexyl Isothiocyanate on Aβ1-42-Induced Cognitive Deficit, Oxidative Stress, Inflammation, and Apoptosis in Mice

2018 ◽  
Vol 19 (7) ◽  
pp. 2083 ◽  
Author(s):  
Fabiana Morroni ◽  
Giulia Sita ◽  
Agnese Graziosi ◽  
Eleonora Turrini ◽  
Carmela Fimognari ◽  
...  
Keyword(s):  
Bioactive Compound ◽  
Biological Properties ◽  
Neuroprotective Activity ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Behavioral Recovery ◽  
Memory Impairments ◽  
Wasabia Japonica

Alzheimer’s disease (AD) is the most common form of dementia among older people. Although soluble amyloid species are recognized triggers of the disease, no therapeutic approach is able to stop it. 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in Wasabia japonica, which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties. The aim of the present study was to investigate the neuroprotective activity of 6-MSITC in a murine AD model, induced by intracerebroventricular injection of β-amyloid oligomers (Aβ1-42O). The treatment with 6-MSITC started 1 h after the surgery for the next 10 days. Behavioral analysis showed that 6-MSITC ameliorated Aβ1-42O-induced memory impairments. The decrease of glutathione levels and increase of reactive oxygen species in hippocampal tissues following Aβ1-42O injection were reduced by 6-MSITC. Moreover, activation of caspases, increase of inflammatory factors, and phosphorylation of ERK and GSK3 were inhibited by 6-MSITC. These results highlighted an interesting neuroprotective activity of 6-MSITC, which was able to restore a physiological oxidative status, interfere positively with Nrf2-pathway, decrease apoptosis and neuroinflammation and contribute to behavioral recovery. Taken together, these findings demonstrated that 6-MSITC could be a promising complement for AD therapy.

scholarly journals Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica)

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Takuhiro Uto ◽  
De-Xing Hou ◽  
Osamu Morinaga ◽  
Yukihiro Shoyama
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Bioactive Compound ◽  
Biological Properties ◽  
Wasabia Japonica ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Oxide Synthase

6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently,in vivoandin vitrostudies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages.

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 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.

scholarly journals Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Yan ◽  
Si-Chi Xu ◽  
Chun-Yan Kong ◽  
Xiao-Yang Zhou ◽  
Zhou-Yan Bian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

scholarly journals Exploring the mechanism of astaxanthin against lipopolysaccharide-induced acute lung injury by network pharmacology and experimental validation

2021 ◽  
Author(s):  
lianxiang luo ◽  
Xiaoling Li ◽  
Riming Huang ◽  
Hui Luo
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Interaction Analysis ◽  
Signal Pathway ◽  
Inflammatory Factors ◽  
Network Pharmacology ◽  
Protective Effects ◽  
Myd88 Signaling

Abstract BackgroundAcute lung injury (ALI) is a leading cause of morbidity and mortality in respiratory disease. Astaxanthin, a natural antioxidant xanthophyll carotenoid, has been shown to possess anti-inflammatory activity. However, poor evidence has been reported that whether it has protective effects against ALI.Methods A network pharmacology analysis was carried out combining the construction of the GeneCards database and the Pharmmapper database, The potential active compounds and targets were predicted by compound-target prediction, protein-protein interaction analysis, GO and KEGG pathway analysis. Then, the anti-inflammation effect of astaxanthin was investigated in LPS-induced RAW264.7 cells in vitro and LPS-induced ALI mice in vivo.ResultsThe results screened by GO and KEGG enrichment analysis suggested that astaxanthin had extensive associations with 25 known therapeutic targets of ALI. These target genes were further found to be associated with pathways involved in inflammatory pathways in ALI, such as the Toll-like receptor signal pathway, TNF signal pathway, Hif signal pathway, and NF-Kappa B signal pathway. Pre-treatment with astaxanthin inhibited the TLR4/MyD88 signaling pathway and attenuated LPS-increased inflammatory factors in vitro. Furthermore, the administration of astaxanthin significantly protected lung injury in vivo. Subsequently, we validated astaxanthin binds to the TLR4 pocket using molecular docking. ConclusionTaken together, astaxanthin exerts impressively protective effects on LPS-induced ALI in vitro and in vivo via suppressing the TLR4/MyD88 signaling pathway.

scholarly journals Anthocyanins: Dietary Sources, Bioavailability, Human Metabolic Pathways, and Potential Anti-Neuroinflammatory Activity

2021 ◽  
Author(s):  
Ruth Hornedo-Ortega ◽  
Zuriñe Rasines-Perea ◽  
Ana B. Cerezo ◽  
Pierre-Louis Teissedre ◽  
Michael Jourdes
Keyword(s):  
Metabolic Pathways ◽  
Fruits And Vegetables ◽  
Biological Properties ◽  
Normal Diet ◽  
Enzymatic Reactions ◽  
Protective Effects ◽  
Realistic Situation ◽  
Brain Parenchymal

The objectives of this chapter are to summarize and discuss (i) the anthocyanins structure and content in foodstuffs and their dietary intake (ii) the anthocyanins bioavailability and human metabolic pathways and (iii) the in vitro and in vivo potent anti-neuroinflammatory effects of anthocyanins and their metabolites. Indeed, anthocyanins are polyphenolic compounds belonging to the group of flavonoids, and are one of the most commonly consumed polyphenols in a normal diet. They are responsible of red, blue and purple color of several fruits and vegetables and their intake has been related with several human health benefits. The anthocyanins structures diversities as well as their content in various fruits, vegetables and cereals is addressed. Moreover, despite the growing evidence for the protective effects of anthocyanins, it is important to highlight that the in vivo bioavailability of these compounds is relatively low in comparison to their more stable metabolites. Indeed, after consumption, these bioactives are subjected to substantial transformations in human body. Phase I and II metabolites generated by intestinal and hepatic enzymatic reactions, and phenolic acids produced by gut microbiota and their metabolized forms, are the most important metabolic anthocyanins forms. For this reason, the study of the biological properties of these circulating metabolites represents a more in vivo realistic situation. Although the anthocyanin bioavailability researches in humans are limited, they will be discussed together with a global metabolic pathway for the main anthocyanins. Moreover, several works have demonstrated that anthocyanins can cross the blood brain barrier, and accumulate in brain endothelial cells, brain parenchymal tissue, striatum, hippocampus, cerebellum and cortex. Consequently, the study of anthocyanins as potent therapeutic agents in neurodegenerative diseases has gained relevance and the principal and the most recent studies are also discussed in the book chapter.

scholarly journals Ameliorative Effects of Loganin on Arthritis in Chondrocytes and Destabilization of the Medial Meniscus-Induced Animal Model

2021 ◽  
Vol 14 (2) ◽  
pp. 135
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Seung Hee Yun ◽  
Seokjin Hwang ◽  
Hyoju Jeon ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Medial Meniscus ◽  
Bioactive Compound ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Protective Effects ◽  
Matrix Metalloproteinase 3 ◽  
Cox 2

Arthritis is a common inflammatory disease that causes pain, stiffness, and joint swelling. Here, we investigated the ameliorative effects of loganin on arthritis in vitro and in vivo. A single bioactive compound was fractionated and isolated from Cornus officinalis (CO) extract to screen for anti-arthritic effects. A single component, loganin, was identified as a candidate. The CO extract and loganin inhibited the expression of factors associated with cartilage degradation, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMP-3), and matrix metalloproteinase 13 (MMP-13), in interukin-1 beta (IL-1β)-induced chondrocyte inflammation. In addition, prostaglandin and collagenase levels were reduced following treatment of IL-1β-induced chondrocytes with loganin. In the destabilization of the medial meniscus (DMM)-induced mouse model, loganin administration attenuated cartilage degeneration by inhibiting COX-2, MMP-3, and MMP-13. Transverse micro-CT images revealed that loganin reduced DMM-induced osteophyte formation. These results indicate that loganin has protective effects in DMM-induced mice.

scholarly journals Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Changwei Yang ◽  
Wuqiong Wang ◽  
Pengxi Deng ◽  
Chen Li ◽  
Liangcai Zhao ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Growth Factor ◽  
Culture System ◽  
Inflammatory Factors ◽  
Fibroblast Growth Factor 21 ◽  
Protective Effects ◽  
Fibroblast Growth ◽  
Microglial Polarization

Microglial polarization and the subsequent neuroinflammatory response were identified as key contributors to the progress of Parkinson's disease (PD). Researchers have shown that fibroblast growth factor 21 (FGF21) plays multiple biological functions, including anti-inflammation and neuroprotection. However, the knowledge of FGF21 on microglial polarization in PD in vivo is far from completion. In this study, both in vivo and in vitro models were used to investigate whether FGF21 enhances the brain function by modulating microglial polarization in PD. The protective effects of FGF21 in vivo were conducted using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice model alongside intraperitoneally received FGF21. A behavioral test battery and tyrosine hydroxylase (TH) immunohistochemistry were conducted to evaluate the neuronal function and nigrostriatal tract integrity. Immunofluorescence assay and Western blot were used to examine M1/M2 microglial polarization. Then, a microglia-neuron co-culture system was adopted in vitro to identify the underlying molecular mechanisms of FGF21. The results showed that FGF21 significantly alleviated motor and cognitive impairment in mice with PD. FGF21 also protected TH-positive neuron cells in the striatum and midbrain. Mechanistically, FGF21 suppressed M1 microglial polarization and the subsequent mRNA expression of pro-inflammatory factors while promoting M2 microglial polarization with increasing anti-inflammatory factors in mice with PD. Furthermore, sirtuin 1 (SIRT1) and the nuclear factor-kappa B (NF-κB) pathway were involved in the FGF21-induced M2 microglial polarization. Conversely, SIRT1 inhibitor EX527 significantly prevented both the FGF21-induced SIRT1 expression and M2 microglial polarization. Moreover, FGF21 pretreatment of microglia significantly prevented neuronal cell apoptosis in a microglia-neuron co-culture system. In conclusion, our data demonstrate that FGF21 exerted its protective effects in the pathology of PD through SIRT1/NF-κB pathway-mediated microglial polarization. Given the safety record of human clinical trials, FGF21 could be a promising therapy for clinical trials to ameliorate motor and nonmotor deficits in patients with PD.

scholarly journals Dehydrocorydaline Protects Against Sepsis-Induced Myocardial Injury Through Modulating the TRAF6/NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yadong Li ◽  
Li Zhang ◽  
Ping Zhang ◽  
Zhiying Hao
Keyword(s):  
Myocardial Injury ◽  
Specific Inhibitor ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
H9c2 Cardiomyocytes ◽  
Stress Functions ◽  
Brdu Assay ◽  
Injury Models

We aim to investigate the effect and mechanism of dehydrocorydaline (Deh), an alkaloidal component isolated from Rhizoma corydalis, in the treatment of sepsis-mediated myocardial injury. Lipopolysaccharide (LPS) was taken to construct an in-vitro sepsis-myocardial injury models H9C2 cardiomyocytes. The in-vivo model of sepsis in C57BL/6 mice was induced by intraperitoneal injection of Escherichia coli (E. coli). The in-vitro and in-vivo models were treated with Deh in different concentrations, respectively. Hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemistry (IHC) staining were taken to evaluate the histopathological changes of the heart. ELISA was applied to evaluate the levels of inflammatory factors, including IL-6, IL-1β, TNFα, IFNγ, and oxidized factors SOD, GSH-PX in the plasma or culture medium. Western blot was used to measure the expressions of Bax, Bcl2, Caspase3, iNOS, Nrf2, HO-1, TRAF6, NF-κB in heart tissues and cells. The viability of H9C2 cardiomyocytes was detected by the CCK8 method and BrdU assay. The ROS level in the H9C2 cardiomyocytes were determined using immunofluorescence. As a result, Deh treatment improved the survival of sepsis mice, reduced TUNEL-labeled apoptosis of cardiomyocytes. In vitro, Deh enhanced the viability of LPS-induced H9C2 cardiomyocytes and inhibited cell apoptosis. Additionally, Deh showed significant anti-inflammatory and anti-oxidative stress functions via decreasing IL-1β, IL-6, TNFα, and IFNγ levels, mitigating ROS level, up-regulating Nrf2/HO-1, SOD, and GSH-PX expressions dose-dependently. Mechanistically, Deh inhibited TRAF6 expression and the phosphorylation of NF-κB p65. The intervention with a specific inhibitor of TRAF6 (C25-140) or NF-κB inhibitor (BAY 11-7082) markedly repressed the protective effects mediated by Deh. In conclusion, Deh restrains sepsis-induced cardiomyocyte injury by inhibiting the TRAF6/NF-κB pathway.

scholarly journals The Protective Effects of Lactobacillus plantarum KLDS 1.0344 on LPS-Induced Mastitis In Vitro and In Vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingxue Chen ◽  
Song Wang ◽  
Jiayao Guo ◽  
Qinggang Xie ◽  
Smith Etareri Evivie ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Pathogenic Bacteria ◽  
Mammary Epithelial ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
E Coli ◽  
Tnf Α

Cow mastitis, which significantly lowers milk quality, is mainly caused by pathogenic bacteria such as E. coli. Previous studies have suggested that lactic acid bacteria can have antagonistic effects on pathogenic bacteria that cause mastitis. In the current study, we evaluated the in vitro and in vivo alleviative effects of L. plantarum KLDS 1.0344 in mastitis treatment. In vitro antibacterial experiments were performed using bovine mammary epithelial cell (bMEC), followed by in vivo studies involving mastitis mouse models. In vitro results indicate that lactic acid was the primary substance inhibiting the E. coli pathogen. Meanwhile, treatment with L. plantarum KLDS 1.0344 can reduce cytokines’ mRNA expression levels in the inflammatory response of bMEC induced by LPS. In vivo, the use of this strain reduced the secretion of inflammatory factors IL-6, IL-1β, and TNF-α, and decreased the activity of myeloperoxidase (MPO), and inhibited the secretion of p-p65 and p-IκBα. These results indicate that L. plantarum KLDS 1.0344 pretreatment can reduce the expression of inflammatory factors by inhibiting the activation of NF-κB signaling pathway, thus exerting prevent the occurrence of inflammation in vivo. Our findings show that L. plantarum KLDS 1.0344 has excellent properties as an alternative to antibiotics and can be developed into lactic acid bacteria preparation to prevent mastitis disease.

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