Search

In the present study, the anti-inflammatory and antisepticemic activities of a water extract of Liriope platyphylla (LP) were investigated. We first estimated the scavenging activity of DPPH and the hydroxyl radical and total phenolic contents of LP. Results indicated that LP, a rich source of phenolic compounds, showed a remarkable radical scavenging capacity. A MTT assay showed that LP treatment did not affect the toxicity against the RAW 264.7 macrophage cells, up to the concentration of 500g/mL. Treatment of LP significantly attenuated the production of inflammatory mediators, such as nitric oxide (NO), interleukin-6 (IL-6), tumor-necrosis factor (TNF)- and prostaglandin (PG)E2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells. Moreover, LP contributed to the down-regulation of inducible NO synthase (iNOS) and TNF- mRNA expression, as well as cyclooxygenase-2 (COX-2) protein expression. A western blotting assay further showed that LP inhibited activation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-B. In an animal experiment using an LPS-induced septicemia model in C57BL/6 mice, oral administration of LP (40mg/kg body weight) markedly reduced the level of TNF- and IL-6 in serum and protected against LPS-induced lethal shock in mice. Taken together, the results of treatments of LP on inhibited LPS-induced inflammatory responses in both in vitro and in vivo models and indicate it may be a promising neutraceutical or medicinal agent to prevent or cure inflammation-related disease. [ABSTRACT FROM AUTHOR]

Stroke is a complex neurodegenerative disorder with a clinically high prevalence and mortality. Despite many efforts to protect against ischemic stroke, its incidence and related permanent disabilities continue to increase. In this study, we found that pretreatment with phlorofucofuroeckol (PFF), isolated from brown algae species, significantly increased cell viability in glutamate-stimulated PC12 cells. Additionally, glutamate-stimulated cells showed irregular morphology, but PFF pretreatment resulted in improved cell morphology, which resembled that in cells cultured under normal conditions. We further showed that PFF pretreatment effectively inhibited glutamate-induced apoptotic cell death in a caspase-dependent manner. Reactive oxygen species (ROS) induced by oxidative stress are closely associated with ischemia-induced neurological diseases. Exposure of PC12 cells to glutamate induced abundant production of intracellular ROS and mitochondrial dysfunction, which was attenuated by PFF in a dose-dependent manner. In vivo studies revealed that PFF-mediated prevention was achieved predominantly through inhibition of apoptosis and mitochondrial ROS generation. Taken together, these results suggest the possibility of PFF as a neuroprotective agent in ischemic stroke. [ABSTRACT FROM AUTHOR]

In this study, the anti-inflammatory and antisepticemic activities of a water extract of aged black garlic (AGE), which is not pungent, were compared with those of raw garlic extract (RGE). The methyl thiazolyl tetrazolium (MTT) assay showed that AGE was not toxic up to 1000 μg/mL and was at least four times less cytotoxic than RGE. AGE significantly suppressed the production of nitric oxide (NO), tumor-necrosis factor- α (TNF- α), and prostaglandin (PG)-E2 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Furthermore, the inhibitory effect of AGE on LPS-induced inflammation was confirmed by downregulation of inducible NO synthase and TNF- α mRNA expression, as well as cyclooxygenase-2 protein expression. The anti-inflammatory activities of AGE were similar to those of RGE at nontoxic concentrations up to 250 μg/mL. Signal transduction pathway studies further indicated that both garlic extracts inhibited activation of mitogen-activated protein kinase and nuclear factor- κB induced by LPS stimulation. Treatment with both AGE and RGE in an in vivo experiment of LPS-induced endotoxemia significantly reduced the level of TNF- α and interleukin-6 in serum and completely protected against LPS-induced lethal shock in C57BL/6 mice. The results suggest that AGE is a more promising nutraceutical or medicinal agent to prevent or cure inflammation-related diseases for safety aspects compared with RGE. [ABSTRACT FROM AUTHOR]

Retinoic acid (RA) plays an important role in the developing mammalian nervous system. Based on this concept, some studies have demonstrated the beneficial effects of RA administration on neurogenesis in neuropathological diseases. Some investigations have revealed the anti-inflammatory effects of RA treatment in multiple systems, in addition to its role in neurogenesis. To date, however, the neuroprotective efficacy of RA after cerebral ischemia, especially in the context of its anti-inflammatory effects, has been poorly demonstrated. Additionally, to the best of our knowledge, experiments of the therapeutic efficacy of RA treatment in a transient global ischemic model in the Mongolian gerbil have been lacking worldwide. Here, we studied the neuroprotective effects and neurobehavioral outcomes of intraperitoneally administered all- trans-RA (ATRA; a synthetic form of RA) on brains with transient global ischemia that was induced with the bilateral common carotid artery occlusion and reperfusion (BCCAO/R) model in the gerbil. In order to identify whether these neuroprotective mechanisms were due to the anti-inflammatory effects of ATRA, in vivo hippocampal expression of proinflammatory cytokines including tissue necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) after ATRA injection and in vitro levels of release of nitric oxide, TNF-α and IL-6 from lipopolysaccharide (LPS)-stimulated BV2 microglial cells after ATRA treatment were evaluated. The results showed that ATRA can protect pyramidal neurons in the hippocampal CA1 region against BCCAO-induced neuronal apoptosis and significantly reduce the extent of astrocytosis and microglial activation. In addition, the ischemia-induced neurobehavioral changes were normalized by ATRA injection. Consistent with these phenotypic data, we observed the diminishing effects of ATRA treatment on the production of proinflammatory mediators (e.g., TNF-α and IL-6) in hippocampal homogenates and LPS-stimulated BV2 cells, and these effects were dose-dependent. These results suggest a beneficial role of ATRA in the attenuation of global cerebral ischemia due to its anti-inflammatory properties, resulting in, at least partly, the inhibition of microglial secretion of variable proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Abstract: Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-α in combination with IFN-γ in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-α-resistant B16/F10.9 melanoma cells. A low dose of TNF-α or IL-6/sIL-6R had minimal affect on the cell growth. However, the highly active fusion protein of sIL-6R and IL-6 (IL6RIL6), covalently linked by a flexible peptide, sensitized TNF-α-resistant F10.9 melanoma cells to TNF-α-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-α resulted in both the activation of caspase-3 and the reduction of bcl-2 expression. Flow cytometry analysis showed that IL6RIL6-upregulated TNF-R55 and TNF-R75 expression, suggesting an increase in TNF-α responsiveness by IL6RIL6 resulting from the induction of TNF receptors. Moreover, exposure of F10.9 cells to neutralizing antibody to TNF-R55 significantly inhibited IL6RIL6/TNF-α-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-α-resistant melanoma cells to TNF-α-induced apoptosis, may provide a new target for immunotherapy. [Copyright &y& Elsevier]

Antitumor and immunomodulatory activities of an aqueous extract (GF100) of Acanthopanax senticosus were examined. In experimental lung metastasis of colon26-M3.1 carcinoma cells, intravenous (i.v.) administration of GF100 2 days before tumor inoculation significantly inhibited lung metastasis in a dose-dependant manner. The i.v. administration of GF100 also exhibited the therapeutic effect on tumor metastasis of colon26-M3.1 cells, when it was injected 1 day after tumor inoculation. In an in vitro cytotoxicity analysis, GF100 at the concentration up to 1000 μg/ml did not affect the growth of colon26-M3.1 cells. In contrast, GF100 enhanced the responsiveness to a mitogen, concanavalin A (ConA), of splenocytes in a dose-dependent manner. Peritoneal macrophage stimulated with GF100 produced various cytokines such as IL-1β, TNF-α, IL-12 and IFN-γ in an in vitro experiment. The macrophages obtained from the mice which were injected with GF100 (500 μg) 3 days before the assay showed significantly higher tumoricidal activity against tumor cells than that of the untreated macrophages. In addition, the i.v. administration of GF100 significantly augmented NK cytotoxicity to Yac-1 cells. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of GF100 on lung metastasis of colon26-M3.1 cells. These data suggest that GF100 has antitumor activity to inhibit tumor metastasis prophylactically as well as therapeutically, and its antitumor effect is associated with activation of macrophages and NK cells. [Copyright &y& Elsevier]

The prevalence of obesity is rapidly increasing and is recognized as a serious health problem. To investigate metabolic changes in an obese model after administration of Acanthopanax sessiliflorus, mice were divided into four groups: normal diet, high-fat diet (HFD), HFD with treatment fenofibrate, and A. sessiliflorus fruit extract. The liver tissue of mice was analyzed using nuclear magnetic resonance (NMR) spectrometry-based metabolomics. In multivariate statistical analyses, the HFD group was discriminated from the normal diet group, and the group fed A. sessiliflorus fruit was discriminated from the HFD group. In biomarker analysis between the HFD group and the group fed A. sessiliflorus fruit, alanine, inosine, formate, pyroglutamate, taurine, and tyrosine, with AUC values of 0.7 or more, were found. The levels of these metabolites were distinguished from the HFD mouse model. Changes in these metabolites were confirmed to act on metabolic pathways related to antioxidant activity. [ABSTRACT FROM AUTHOR]

The ginseng berry contains a variety of biologically active compounds and has a higher ginsenoside content than its roots. This study focused on the hepatoprotective activity of ginseng berry extract prepared by enzyme treatment (EGB) compared to the non-enzyme-treated ginseng berry extract (GB) and quality control of EGB. The feeding effect of EGB on alcohol-induced liver damage (AILD) was investigated by measuring the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with those of EtOH-fed mice. Furthermore, cytokine levels in the culture supernatants of EGB- or GB-treated RAW 264.7 cells were determined by enzyme-linked immunosorbent assay. The developed method was applied to the simultaneous quantification of four major ginsenosides in EGB using UPLC-QTOF/MS. Treatment with EGB at a dose of 0.5 or 1 mg/mouse significantly suppressed the AST and ALT levels in mice with AILD. Enzyme-treated ginseng berry was also found to suppress the production of inflammatory mediators like nitric oxide (NO), tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, showing higher activity than that of GB. The amount of ginsenoside Re, F5, F3, and Rd in the EGB obtained using UPLC-QTOF/MS was 45.9, 3.3, 4.0, and 6.2 mg/g, respectively. These results suggest that EGB has a potential effect on AILD, and its hepatoprotective effect provides beneficial insights into developing new candidates for the prevention and cure of AILD. Also, this study demonstrated the utility of UPLC-QTOF/MS-based major compounds for quality control (QC) of EGB. [ABSTRACT FROM AUTHOR]

Heat-killed Saccharomyces cerevisiae (HKSC) is an agonist for Dectin-1, a major fungal cell wall β-glucan receptor. We previously reported that HKSC selectively enhances IgG1 production by LPS-activated mouse B cells. To determine if this IgG1 selectivity is caused by selective IgG1 class switching, we performed RT-PCRs for measuring germline transcripts (GLTs), flow cytometric analyses for detecting Ig-expressing cells, and ELISPOT assays for measuring the number of Ig-secreting cells in HKSC/LPS-stimulated mouse B cell cultures. HKSC selectively enhanced expression of GLTγ1, the number of IgG1-expressing cells, and the number of IgG1-secreting B cells in the presence of LPS stimulation. In addition, HKSC induced the expression of CD69, an activation marker for B lymphocytes, and the expression of surface Dectin-1. Two Dectin-1 antagonists, laminarin and a neutralizing Dectin-1 antibody, selectively diminished HKSC-reinforced IgG1 production by LPS-stimulated B cells. Furthermore, depleted zymosan (dzn), a Dectin-1 agonist with increased selectivity, also selectively enhanced GLTγ1 transcription. The Dectin-1 antagonists blocked dzn-induced IgG1 production by LPS-activated B cells. Collectively, these results suggest that Dectin-1 agonists selectively induce IgG1 class switching by direct stimulation of Dectin-1 on LPS-activated B cells resulting in selective production of IgG1. [ABSTRACT FROM AUTHOR]

We studied the blood–brain barrier (BBB) permeability and intracellular localization of a fluorescein isothiocyanate (FITC)-labeled dieckol ( 1 ) and a rhodamine B-labeled dieckol ( 7 ), for exploring the possible therapeutic application of fluorone-labeled dieckols in neurodegenerative diseases. Both compounds ( 1 & 7 ) were synthesized through a click reaction and were found to be localized in the endoplasmic reticulum (ER) of the two types of brain cell lines (SH-SY5Y and BV-2 cells) tested; they also reduced ER stress in the SH-SY5Y human neuroblastoma cells. In addition, 1 and 7 were shown to pass the BBB in rats upon intravenous administration. Altogether, our study demonstrates, for the first time, that targeted ER-stress reduction in brain cells can be achieved by introducing fluorone–dieckol conjugates into systemic circulation. Therefore, 1 and 7 provide a novel and promising ER-targeting therapeutic strategy for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

• Alcohol alone administration altered hippocampal memory and long-term potentiation. • Nicotine alone administration did not change hippocampal functions in control mice. • Beneficial effects of nicotine on alcohol induced memory and LTP impairments. Alcohol and nicotine are routinely abused together. There is one plausible explanation that comorbidity can alleviate alcohol-induced cognitive impairment. However, the mechanism involved is not known. The aim of this report was to evaluate the interactive effects of alcohol coadministration with nicotine on hippocampal memory and long-term potentiation (LTP). C57BL/6 mice were distributed into 4 treatment groups: control, alcohol, nicotine, and alcohol plus nicotine. All mice received tap water or alcohol solution and saline or nicotine. In water maze test, the alcohol group showed significant decreases in hippocampus function and acquisition training than control, nicotine, and combined treatment groups. The alcohol group also showed a significantly shorter latency in entering the foot-shock compartment than control, nicotine, and combined treatment groups in a passive avoidance test. Theta burst stimulation was adopted to induce concrete LTP in CA1 field recording using hippocampal slice. Alcohol alone administration failed to maintain LTP. Nicotine alone administration did not alter hippocampal LTP. There were no negative effects of alcohol on hippocampal LTP in mice administrated with nicotine. The current study successfully demonstrated beneficial effects of nicotine on alcohol induced memory impairment accompanied by hippocampal LTP impairment after one week of co-administration and one-day withdrawal. [ABSTRACT FROM AUTHOR]

Abstract: The present study was attempted to evaluate the effects of gamma-irradiated doxorubicin (IRD) on spleen cell proliferation, cytokines release (IFN-γ and IL-2) and lung metastasis in mice. Gamma irradiation induced degradation of doxorubicin molecule and cytotoxicity on melanoma (B16BL6) and myoblast (H9c2) cell lines were determined by high performance liquid chromatography (HPLC) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazole) assay, respectively. Non-irradiated doxorubicin (NIRD) was used as a control. The mice injected with NIRD (2mg/kg body weight for 5 days, 24h interval) showed a considerable decrease (P <0.05) in the body, spleen weight, proliferation and cytokine release (IL-2 and IFN-γ) as compared to control. However, a non-significant variation was observed in IRD treated mice compared with normal. Tumor bearing mice treated with NIRD and IRD (2mg/kg body weight, five doses at 48h interval) showed diverse results on spleen cell cytokine release, proliferation and metastasis. HPLC results revealed the formation of several trace level degradation (P <0.05) products of IRD. IRD displayed a non-significant variation of cytotoxicity on B16BL6 cells, and low percentage (P < 0.01) of cardiotoxicity on H9c2 cells as compared to NIRD. Altogether, this present study emphasis that gamma irradiation altered the property of doxorubicin. [Copyright &y& Elsevier]

Abstract: To clarify the mechanisms and factors involved in the regulation of mouse IL-2Rβ gene expression, we isolated the 5′-flanking region of IL-2Rβ gene and investigated the promoter activity. Here we elucidated the positive regulatory regions, the most potent of which are located between −50 to −30bp and −164 to −135bp. These regions contain a potentially functional Ets and Egr-1-binding sites whose mutations abrogate promoter activity. Data from electrophoretic mobility shift assay indicate that Ets and Egr-1, but not Sp1, bind to the positive regulatory regions, −50 to −30bp and −164 to −135bp, respectively. Furthermore, recruitment of Ets and Egr-1 at endogenous IL-2Rβ promoter segments in an IL-2-dependent F7 cells was verified by the chromatin immunoprecipitation assay. This study for the first time delineates the molecular mechanisms underlying regulation of mouse IL-2Rβ gene transcription by Ets family proteins, partially with Egr-1, and thereby further elucidates the molecular basis of lymphocyte activation and differentiation. [Copyright &y& Elsevier]

Focal cerebral ischemia (fCI) can result in brain injury and sensorimotor deficits. Brown algae are currently garnering scientific attention as potential therapeutic candidates for fCI. This study investigated the therapeutic effects of the hot water extract of Petalonia binghamiae (wPB), a brown alga, in in vitro and in vivo models of fCI. The neuroprotective efficacy of wPB was evaluated in an in vitro excitotoxicity model established using HT-22 cells challenged with glutamate. Afterward, C57/BL6 mice were administered wPB for 7 days (10 or 100 mg/kg, intragastric) and subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) operation, which was used as an in vivo fCI model. wPB co-incubation significantly inhibited cell death, oxidative stress, and apoptosis, as well as stimulated the expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, and the nuclear translocation of its upstream regulator, nuclear factor erythroid 2-related factor 2 (Nrf2) in HT-22 cells challenged with glutamate-induced excitotoxicity. Pretreatment with either dose of wPB significantly attenuated infarction volume, neuronal death, and sensorimotor deficits in an in vivo fCI model. Furthermore, the attenuation of oxidative stress and apoptosis in the ischemic lesion accompanied the wPB-associated protection. This study suggests that wPB can counteract fCI via an antioxidative effect, upregulating the Nrf2/HO-1 pathway.

Alzheimer's disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM)- Phellinus linteus , Ganoderma lucidum , and Inonotus obliquus -cultivated on a barley medium was assessed for its anti-AD effects. Neuron-like PC12 cells, which were subjected to Zn 2+ , an Aβ aggregator, were employed as an in vitro AD model. The cells pretreated with or without MMMM were assayed for Aβ immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. Then, 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aβ immunofluorescence, ROS accumulation, and apoptosis, and incrementation in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aβ plaque accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aβ plaque accumulation and neuroinflammation, by impeding Aβ-induced neurotoxicity.