Vascular endothelial function is improved by oral glycine treatment in aged rats

2015 ◽  
Vol 93 (6) ◽  
pp. 465-473 ◽  
Author(s):  
Jaime H. Gómez-Zamudio ◽  
Rebeca García-Macedo ◽  
Martha Lázaro-Suárez ◽  
Maximiliano Ibarra-Barajas ◽  
Jesús Kumate ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Interleukin 1 ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Response Curves ◽  
Proinflammatory Mediators ◽  
Nadph Oxidase 4 ◽  
Tnf Α ◽  
Cox 2

Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague–Dawley rats at 5 and 15 months of age. Concentration–response curves to phenylephrine (PHE) were obtained from aortic rings incubated with NG-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT–PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.

Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation

2006 ◽  
Vol 291 (3) ◽  
pp. F567-F577 ◽  
Author(s):  
Li-Mei Chen ◽  
Cindy Wang ◽  
Mengqian Chen ◽  
Matthew R. Marcello ◽  
Julie Chao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Inducible Nitric Oxide Synthase ◽  
Cytokine Signaling ◽  
Bladder Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Prostasin is a glycosylphosphatidylinositol-anchored serine protease, with epithelial sodium channel activation and tumor invasion suppression activities. We identified the bladder as an expression site of prostasin. In the mouse, prostasin mRNA expression was detected by reverse transcription and real-time polymerase chain reaction in the bladder, and the prostasin protein was localized by immunohistochemistry in the urothelial cells. In mice injected intraperitoneally with bacterial lipopolysaccharide (LPS), bladder prostasin mRNA expression was downregulated, whereas the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-γ (IFN-γ), TNF-α, IL-1β, and IL-6 was upregulated. Viral promoter-driven expression of the human prostasin homolog in the bladder of transgenic mice attenuated the LPS induction of iNOS but did not abolish the induction. LPS induction of COX-2, TNF-α, IL-1β, and IL-6 expression, however, was not reduced by prostasin transgene expression. Liposome-mediated delivery of prostasin-expressing plasmid into mouse bladder produced similar attenuation effects on LPS-induced iNOS expression, while not affecting COX-2 or cytokine induction. Mice receiving plasmid expressing a catalytic mutant prostasin did not manifest the iNOS induction attenuation phenotype. We propose a proteolytic mechanism for prostasin to intercept cytokine signaling during LPS-induced bladder inflammation.

Anti-Inflammatory Effects of Trilinolein from Panax notoginseng Through the Suppression of NF-κB and MAPK Expression and Proinflammatory Cytokine Expression

2014 ◽  
Vol 42 (06) ◽  
pp. 1485-1506 ◽  
Author(s):  
Shyh-Shyun Huang ◽  
Jeng-Shyan Deng ◽  
Jaung-Geng Lin ◽  
Chao-Ying Lee ◽  
Guan-Jhong Huang
Keyword(s):  
Nitric Oxide ◽  
Western Blotting ◽  
Mapk Pathway ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Paw Edema ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

In this study, we have investigated the anti-inflammatory effects of trilinolein (TL) using a lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) and carrageenan (Carr)-induced mouse paw edema model. When RAW264.7 macrophages were treated with different concentrations of TL together with LPS, a significant concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1 (IL-1β), and IL-6 production was detected. Western blotting revealed that TL blocked the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), IκBα, and mitogen-activated protein kinases (MAPKs). In the anti-inflammatory test, TL decreased the paw edema at the 5th h after λ-Carr administration in paw edema. We also demonstrated TL significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. TL decreased the NO and TNF-α levels on the serum level at the 5th h after Carr injection. Western blotting revealed that TL decreased Carr-induced iNOS and COX-2 expressions at the 5th h in the edema paw. The anti-inflammatory mechanisms of TL might be related to the decrease in the level of iNOS, COX-2, IκBα, and MAPK pathway through the suppression of TNF-α, IL-1β, and IL-6.

scholarly journals Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism

2008 ◽  
Vol 295 (5) ◽  
pp. R1486-R1493 ◽  
Author(s):  
Tim Lahm ◽  
Paul R. Crisostomo ◽  
Troy A. Markel ◽  
Meijing Wang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Estrogen Receptor ◽  
Pulmonary Artery ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Organ Bath ◽  
Sprague Dawley ◽  
Response Curves ◽  
Vascular Effects ◽  
M 10 ◽  
Dependent Mechanism

Both endogenous and exogenous estrogen decrease pulmonary artery (PA) vasoconstriction. Whether these effects are mediated via estrogen receptor (ER)-α or ER-β, and whether the contribution of ERs is stimulus-dependent, remains unknown. We hypothesized that administration of the selective ER-α agonist propylpyrazole triol (PPT) and/or the selective ER-β agonist diarylpropiolnitrile (DPN) rapidly decreases PA vasoconstriction induced by pharmacologic and hypoxic stimuli via a nitric oxide (NO)-dependent mechanism. PA rings ( n = 3–10/group) from adult male Sprague-Dawley rats were suspended in physiologic organ baths. Force displacement was measured. Vasoconstrictor responses to phenylephrine (10−8M − 10−5M) and hypoxia (Po2 35–45 mmHg) were determined. Endothelium-dependent and -independent vasorelaxation were measured by generating dose-response curves to acetylcholine (10−8M − 10−4M) and sodium nitroprusside (10−9M − 10−5M). PPT or DPN (10−9M − 5 × 10−5M) were added to the organ bath in the presence and absence of the NO-synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) (10−4M). Selective ER-α activation (PPT, 5 × 10−5M) rapidly (<20 min) decreased phenylephrine-induced vasoconstriction. This effect, as well as PPT's effects on endothelium-dependent vasorelaxation, were neutralized by l-NAME. In contrast, selective ER-β activation (DPN, 5 × 10−5M) rapidly decreased phase II of hypoxic pulmonary vasoconstriction (HPV). l-NAME eliminated this phenomenon. Lower PPT or DPN concentrations were less effective. We conclude that both ER-α and ER-β decrease PA vasoconstriction. The immediate onset of effect suggests a nongenomic mechanism. The contribution of specific ERs appears to be stimulus specific, with ER-α primarily modulating phenylephrine-induced vasoconstriction, and ER-β inhibiting HPV. NO inhibition eliminates these effects, suggesting a central role for NO in mediating the pulmonary vascular effects of both ER-α and ER-β.

scholarly journals Sargassum fulvellumProtects HaCaT Cells and BALB/c Mice from UVB-Induced Proinflammatory Responses

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chan Lee ◽  
Gyu Hwan Park ◽  
Eun Mi Ahn ◽  
Chan-Ik Park ◽  
Jung-Hee Jang
Keyword(s):  
Nitric Oxide ◽  
Ethanol Extract ◽  
Prostaglandin E ◽  
Hacat Cells ◽  
Uvb Irradiation ◽  
Proinflammatory Mediators ◽  
Sargassum Fulvellum ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Skin Damages

Ultraviolet (UV) radiation has been reported to induce cutaneous inflammation such as erythema and edema via induction of proinflammatory enzymes and mediators.Sargassum fulvellumis a brown alga of Sargassaceae family which has been demonstrated to exhibit antipyretic, analgesic, antiedema, antioxidant, antitumor, fibrinolytic, and hepatoprotective activities. The purpose of this study is to investigate anti-inflammatory effects of ethylacetate fraction of ethanol extract ofSargassum fulvellum(SFE-EtOAc) in HaCaT keratinocytes and BALB/c mice. In HaCaT cells, SFE-EtOAc effectively inhibited UVB-induced cytotoxicity (60 mJ/cm2) and the expression of proinflammatory proteins such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α(TNF-α), and inducible nitric oxide synthase (iNOS). Furthermore, SFE-EtOAc significantly reduced UVB-induced production of proinflammatory mediators including prostaglandin E2(PGE2) and nitric oxide (NO). In BALB/c mice, topical application of SFE-EtOAc prior to UVB irradiation (200 mJ/cm2) effectively suppressed the UVB-induced protein expression of COX-2, iNOS, and TNF-αand subsequently attenuated generation of PGE2and NO as well. In another experiment, SFE-EtOAc pretreatment suppressed UVB-induced reactive oxygen species production and exhibited an antioxidant potential by upregulation of antioxidant enzymes such as catalase and Cu/Zn-superoxide dismutase in HaCaT cells. These results suggest that SFE-EtOAc could be an effective anti-inflammatory agent protecting against UVB irradiation-induced skin damages.

scholarly journals Microglia is a Key Player in the Reduction of Stroke Damage Promoted by the New Antithrombotic Agent Ticagrelor

2014 ◽  
Vol 34 (6) ◽  
pp. 979-988 ◽  
Author(s):  
Paolo Gelosa ◽  
Davide Lecca ◽  
Marta Fumagalli ◽  
Dorota Wypych ◽  
Alice Pignieri ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Interleukin 1 ◽  
Artery Occlusion ◽  
Cerebral Injury ◽  
Sprague Dawley ◽  
Antithrombotic Agent ◽  
Fluorescent Reporter ◽  
Monocyte Chemoattractant Protein 1 ◽  
Proinflammatory Mediators ◽  
Green Fluorescent

The ADP-responsive P2Y12 receptor is expressed on both platelets and microglia. Clinical data show that ticagrelor, a direct-acting, reversibly binding P2Y12-receptor antagonist, reduces total cardiovascular events, including stroke. In our present study, we investigated the expression of P2Y12 receptors and the effects of ticagrelor on brain injury in Sprague-Dawley rats subjected to a permanent middle cerebral artery occlusion (MCAo). Rats were treated per os with ticagrelor 3 mg/kg or vehicle at 10 minutes, 22, and 36 hours after MCAo and killed after 48 hours. Immunofluorescence analysis showed an ischemia-related modulation of the P2Y12 receptor, which is constitutively expressed in Iba1+ resting microglia. After MCAo, activated microglia was mainly concentrated around the lesion, with fewer cells present inside the ischemic core. Ticagrelor significantly attenuated the evolution of ischemic damage—evaluated by magnetic resonance imaging (MRI) at 2, 24, and 48 hours after MCAo—, the number of infiltrating cells expressing the microglia/monocyte marker ED-1, the cerebral expression of proinflammatory mediators (interleukin 1 (IL-1), monocyte chemoattractant protein 1 (MCP-1), nitric oxide synthase (iNOS)) and the associated neurologic impairment. In transgenic fluorescent reporter CX3CR1-green fluorescent protein (GFP) mice, 72 hours after MCAo, ticagrelor markedly reduced GFP+ microglia and both early and late infiltrating blood-borne cells. Finally, in primary cultured microglia, ticagrelor fully inhibited ADP-induced Chemotaxis ( P<0.01). Our results show that ticagrelor is protective against ischemia-induced cerebral injury and this effect is mediated, at least partly, by inhibition of P2Y12-mediated microglia activation and Chemotaxis.

Oxymatrine inhibits lipopolysaccharide-induced inflammation by down-regulating Toll-like receptor 4/nuclear factor-kappa B in macrophages

2015 ◽  
Vol 93 (4) ◽  
pp. 253-260 ◽  
Author(s):  
Yu Zhang ◽  
Ruhong Yan ◽  
Yae Hu
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Chinese Herb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Anti Inflammatory

Oxymatrine (OMT) is the quinolizidine alkaloid extracted from the Chinese herb Sophora flavescens Ait. that has many pharmacological effects and is used for the treatment of some inflammatory diseases. In this study, RAW264.7 cells and THP-1 differentiated macrophages were pretreated with various concentrations of OMT at 2 h prior to treatment with lipopolysaccharide (LPS) (1.0 μg/mL) for different durations. We detected the anti-inflammatory effect of OMT in LPS-stimulated macrophages and investigated the molecular mechanism. We showed that OMT pretreatment significantly inhibited the LPS-induced secretion of nitric oxide (NO), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) in supernatant, attenuated the mRNA levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and Toll-like receptor 4 (TLR4), increased TLR4 and phosphorylation of inhibitor of kappa B-alpha (p-IBα) in cytosol, and decreased the nuclear level of nuclear factor-κB (NF-κB) p65 in macrophages. In conclusion, OMT exerts anti-inflammatory properties in LPS-stimulated macrophages by down-regulating the TLR4/NF-κB pathway.

scholarly journals Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

2019 ◽  
Vol 20 (14) ◽  
pp. 3574 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong
Keyword(s):  
Mrna Expression ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Tnf Α ◽  
Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

scholarly journals Inhibitory Effect of 1,5-Dimethyl Citrate from Sea Buckthorn (Hippophae rhamnoides) on Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Mouse Macrophages

Foods ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 269 ◽  
Author(s):  
Su Cheol Baek ◽  
Dahae Lee ◽  
Mun Seok Jo ◽  
Kwang Ho Lee ◽  
Yong Hoon Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sea Buckthorn ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Cox 2 ◽  
Oxide Synthase

Hippophae rhamnoides L. (Elaeagnaceae; commonly known as “sea buckthorn” and “vitamin tree”), is a spiny deciduous shrub whose fruit is used in foods and traditional medicines. The H. rhamnoides fruit (berry) is rich in vitamin C, with a level exceeding that found in lemons and oranges. H. rhamnoides berries are usually washed and pressed to create pomace and juice. Today, the powder of the aqueous extract of H. rhamnoides berries are sold as a functional food in many countries. As part of our ongoing effort to identify bioactive constituents from natural resources, we aimed to isolate and identify those from the fruits of H. rhamnoides. Phytochemical analysis of the extract of H. rhamnoides fruits led to the isolation and identification of six compounds, namely, a citric acid derivative (1), a phenolic (2), flavonoids (3 and 4), and megastigmane compounds (5 and 6). Treatment with compounds 1–6 did not have any impact on the cell viability of RAW 264.7 mouse macrophages. However, pretreatment with these compounds suppressed lipopolysaccharide (LPS)-induced NO production in RAW 264.7 mouse macrophages in a concentration-dependent manner. Among the isolated compounds, compound 1 was identified as the most active, with an IC50 of 39.76 ± 0.16 μM. This value was comparable to that of the NG-methyl-L-arginine acetate salt, a nitric oxide synthase inhibitor with an IC50 of 28.48 ± 0.05 μM. Western blot analysis demonstrated that compound 1 inhibited the LPS-induced expression of IKKα/β (IκB kinase alpha/beta), I-κBα (inhibitor of kappa B alpha), nuclear factor kappa-B (NF-κB) p65, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) in RAW 264.7 cells. Furthermore, LPS-stimulated cytokine production was detected using a sandwich enzyme-linked immunosorbent assay. Compound 1 decreased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) production in LPS-stimulated RAW 264.7 cells. In summary, the mechanism of action of 1 included the suppression of LPS-induced NO production in RAW 264.7 cells by inhibiting IKKα/β, I-κBα, NF-κB p65, iNOS, and COX-2, and the activities of IL-6 and TNF-α.

scholarly journals Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989243
Author(s):  
HaiZou bo ◽  
XiaoSun feng
Keyword(s):  
Lung Injury ◽  
Mrna Expression ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Post Treatment ◽  
Inflammatory Factors ◽  
Pulmonary Injury ◽  
Pathological Changes ◽  
Sprague Dawley ◽  
Tnf Α

Objective To investigate the influence of curcumin on the Notch2/Hes-1 pathway after pulmonary injury induction via limb ischemia–reperfusion (I/R). Methods Adult male Sprague–Dawley rats were randomly divided into four groups (n = 30 each): sham, I/R, curcumin post-treatment (I/R+Cur), and inhibitor (I/R+DAPT). Hind-limb ischemia was induced for 4 hours, followed by reperfusion for 4 hours. After ischemia, curcumin (200 mg/kg) or DAPT (0.5 µm) was injected intraperitoneally in the I/R+Cur or I/R+DAPT group, respectively. PaO2 was examined after 4 hours of reperfusion. Pathological changes in the lung and the apoptotic index (AI) were examined. Lung malondialdehyde (MDA), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β levels, the wet/dry (W/D) ratio, semi-quantitative score of lung injury (SSLI), and Notch2 protein and Hes-1 mRNA expression were also examined. Results In the I/R group, inflammatory changes were observed, AI increased, and MDA, SSLI, W/D, TNF-α, IL-1β, Notch2, and Hes1-mRNA expression increased, while PaO2 decreased compared with the Sham group. Pathological changes in the I/R+Cur group were reversed. All indexes in the I/R+DAPT and I/R+Cur group were similar. Conclusion Curcumin post-treatment reduced I/R-induced lung injury in rats. Its mechanism may be related to the inhibition of Notch2/Hes-1 signaling pathway and the release of inflammatory factors.

scholarly journals Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096399
Author(s):  
Guixiang Liao ◽  
Zhihong Zhao ◽  
Hongli Yang ◽  
Xiaming Li
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Ht22 Cells ◽  
Tnf Α ◽  
Radiation Induced ◽  
Cox 2

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

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