• Nutrition Research and Practice
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• 제14권6호
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• pp.593-605
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• 2020

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and Aβ_25-35, and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot. RESULTS: Aβ_25-35 significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ_25-35-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.

• Journal of Chest Surgery
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• 제51권2호
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• pp.114-121
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• 2018

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.

• Clinical and Experimental Reproductive Medicine
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• 제44권4호
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• pp.214-223
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• 2017

Objective: In vitro fertilization (IVF) is a well-known method for the treatment of infertility. The present study aimed to compare the differences between infertile women with successful and unsuccessful IVF outcomes regarding the expression of T helper (Th) cell transcription factors and a group of related cytokines before and after exposure to their husbands' seminal plasma. Methods: This study was performed on 19 couples with unexplained infertility undergoing IVF treatment. Among the studied group, nine and 10 couples had successful and unsuccessful IVF outcomes, respectively. This study was carried out using real-time polymerase chain reaction. Results: Before seminal plasma exposure, the expression levels of T-bet (p< 0.007), $interferon-{\gamma}$ (p= 0.013), and tumor necrosis factor $(TNF)-{\alpha}$ (p= 0.017) were higher in the infertile women with IVF failure than in those with successful IVF outcomes, while those of GATA3 (p< 0.001), Foxp3 (p= 0.001), and interleukin (IL)-35 (p< 0.003) were lower. After seminal exposure, the expression of T-bet (p= 0.02), Rorc (p< 0.001), $TNF-{\alpha}$ (p= 0.001), Foxp3 (p= 0.02), and $interferon-{\gamma}$ (p= 0.001) increased in the unsuccessful IVF group, while the expression of Foxp3 (p= 0.02), Rorc (p< 0.001), IL-23 (p= 0.04), IL-17 (p= 0.02), IL-6 (p< 0.001), transforming growth $factor-{\beta}$ (p= 0.01), and IL-35 (p< 0.001) increased in the successful IVF group. Conclusion: In summary, IVF failure was associated with imbalanced Th1/Th2/Th17/Treg responses. Moreover, our results show that seminal plasma might have a positive effect on IVF outcomes via changes in peripheral blood T cell subsets.

• Natural Product Sciences
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• 제24권3호
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• pp.148-154
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• 2018

Chronic oxidative stress due to the accumulation of reactive oxygen species (ROS) in neuronal cells ultimately leads to neurodegenerative diseases. The use of natural therapies for the prevention of ROS-induced cell damage and for the treatment of neurodegenerative disorders has shown promising results. In this study, we evaluated the neuroprotective effects of the ethyl acetate (EtOAc) fraction of A. okamotoanum against the hydrogen peroxide ($H_2O_2$)-induced oxidative stress in C6 glial cells. Results show that cell viability was decreased in cells incubated with $H_2O_2$, whereas the addition of EtOAc fraction treatments in such cells significantly increased viability. The EtOAc fraction showed the highest inhibitory activity against ROS production and it also decreased the expressions of inflammatory proteins including cyclooxygenase-2, inducible nitric oxide synthase and interleukin-$1{\beta}$. Furthermore, the EtOAc fraction inhibited apoptosis by regulating the protein expressions cleaved caspase -9, -3, poly ADP ribose polymerase, Bax and Bcl-2. Therefore, these results show that the EtOAc fraction of A. Okamotoanum exhibits neuroprotective effects against $H_2O_2$ induced oxidative damage by regulating the inflammatory reaction and apoptotic pathway.

• Journal of Oral Medicine and Pain
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• 제41권3호
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• pp.126-132
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• 2016

Purpose: The aims of this study were to analyze the association between inflammatory cytokine and obstructive sleep apnea (OSA), and to evaluate treatment outcome and changes of plasma inflammatory cytokine levels after oral appliance therapy. Methods: Twenty-seven subjects who visited Department of Oral Medicine in Seoul National University Dental Hospital were performed nocturnal polysomnography and analyzed plasma C-reactive protein (CRP), interleukin (IL)-$1{\beta}$, IL-6, IL-10, and tumor necrosis factor (TNF)-${\alpha}$ levels. Each subject was evaluated with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). The subjects were classified into 12 OSA patients (apnea-hypopnea index [AHI] >5) and 15 control (AHI ${\leq}5$) groups. The OSA group was treated with mandibular advancement device (MAD) for 3 months and re-evaluated nocturnal polysomnography and plasma inflammatory cytokine levels. Results: Plasma TNF-${\alpha}$, IL-10, and IL-6 levels were significantly higher in OSA patients compared to controls. Total AHI showed significant positive correlations with plasma IL-6 and TNF-${\alpha}$ levels. Percentage time of $SpO_2$ <90 and lowest $SpO_2$ were significantly correlated with plasma TNF-${\alpha}$ level. ESS showed significant positive correlation with plasma IL-10 level. Total AHI, percentage time of $SpO_2$ <90, lowest $SpO_2$, and mean $SpO_2$ were significantly improved after the MAD therapy. Plasma TNF-${\alpha}$ level was significantly decreased after MAD therapy. Conclusions: We suggest that MAD therapy is an effective treatment modality for patients with OSA and can decrease plasma cytokine level.

• KSBB Journal
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• 제30권6호
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• pp.326-331
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• 2015

The anti-inflammatory effect of tuna heart water extract (THWE) was investigated using lipopolysaccharide-induced inflammatory response in this study. Anti-inflammatory effect was detected by the cell proliferation and the production levels of nitric oxide, pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-$1{\beta}$, and tumor necrosis factor-alpha. As a result, there were no cytotoxic effects on proliferation of macrophages treated with THWE compared to the control. The production of pro-inflammatory cytokines was remarkably suppressed compared with that of the LPS only group. These results suggest that THWE exerts the anti-inflammatory property by inhibiting production of inflammatory factors and may be a potential material for anti-inflammatory therapy.

• 한국식품영양학회지
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• 제22권4호
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• pp.517-525
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• 2009

This study investigated the effects of Angelica keiskei Koidzumi and turmeric extract supplementation(ATE) on blood lipids, antioxidant and inflammatory markers in 35 hypercholesterolemic Korean adults with high blood cholesterol levels (serum total cholesterol$\geq200mg/d{\ell}$ or LDL-cholesterol$\geq130mg/d{\ell}$). They received ATE(n=21, 14 females and 7 males) or placebo(control group, n=14, 11 females and 3 males) for 4 weeks. There was no significant change in serum total cholesterol, LDL-cholesterol and HDL-cholesterol levels after ATE supplementation in the both groups. However, the LDLcholesterol: HDL-cholesterol ratio(LPH) was significantly decreased and both serum prostagrandin E2(PGE2) levels were significantly decreased in those receiving ATE. No significant changes were evident in interleukin(IL)-$1\beta$, IL-6, IL-8, 8-isoprostane, malondialehyde, total antioxidant capacity and oxidized-LDL. These results suggest that complex extract of Angelica keiske and turmeric has the potential to decrease cardiovascular risk by reducing LPH and inflammatory mediator $PGE_2$ in hypercholesterolemic adults.

• Mycobiology
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• 제43권2호
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• pp.131-136
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• 2015

The basidiomycete Laetiporus sulphureus var. miniatus belongs to the Aphyllophorales, Polyporaceae, and grows on the needleleaf tree. The fruiting bodies of Laetiporus species are known to produce N-methylated tyramine derivatives, polysaccharides, and various lanostane triterpenoids. As part of our ongoing effort to discover biologically active compounds from wood-rotting fungi, an anti-inflammatory triterpene, LSM-H7, has been isolated from the fruiting body of L. sulphureus var. miniatus and identified as acetyl eburicoic acid. LSM-H7 dose-dependently inhibited the NO production in RAW 264.7 cells without any cytotoxicity at the tested concentrations. Furthermore it suppressed the production of proinflammatory cytokines, mainly inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor ${\alpha}$, when compared with glyceraldehyde 3-phosphate dehydrogenase. These data suggest that LSM-H7 is a crucial component for the anti-inflammatory activity of L. sulphureus var. miniatus.

• Biomolecules & Therapeutics
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• 제21권5호
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• pp.381-390
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• 2013

The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-1${\beta}$, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.79-89
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• 2012

We examine whether Phellodendron amurense (PA) and its major alkaloid compound, berberine (BER), improved memory defects caused by administering scopolamine in rats. Effects of PA and BER on the acetylcholinergic system and pro-inflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of PA (100 and 200 mg/kg, i.p.) and BER (20 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of PA and BER improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Administration of PA and BER significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus. PA and BER also decreased significantly the expression of proinflammatory cytokines such as interleukin-$1{\beta}$, tumor necrosis factor-${\alpha}$ and cyclooxygenase-2 mRNA in the hippocampus. These results demonstrated that PA and BER had significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that PA and BER may be useful as therapeutic agents for improving cognitive functioning by stimulating cholinergic enzyme activity and alleviating inflammatory responses.