Jin Tae Hong

Chonnam National University, Gwangju, Gwangju, South Korea

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Publications (330)932.49 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia. It is characterized by beta-amyloid (Aβ) peptide fibrils, which are extracellular depositions of a specific protein, and is accompanied by extensive neuroinflammation. Various studies have demonstrated risk factors that can affect AD pathogenesis, and they include accumulation of Aβ, hyperphosphorylation of tau protein, and neuroinflammation. Among these detrimental factors, neuroinflammation has been highlighted by epidemiologic studies suggesting that use of anti-inflammatory drugs could significantly reduce the incidence of AD. Evidence suggests that astrocytes, microglia, and infiltrating immune cells from periphery might contribute to or modify the process of neuroinflammation and neurodegeneration in AD brains. In addition, recent data indicate that microRNAs may affect neuroinflammatory responses in the brain. This article focuses on supportive evidence that neuroinflammation plays a critical role in AD development. In addition, we depict putative therapeutic capacity of anti-inflammatory drugs for AD prevention or treatment. We also discuss pathogenic mechanisms by which astrocytes, microglia, T cells and microRNA participate in AD and the neuroprotective mechanisms of anti-inflammatory drugs.
    Archives of Pharmacal Research 08/2015; DOI:10.1007/s12272-015-0648-x · 1.75 Impact Factor
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    ABSTRACT: Peroxiredoxin 6 (Prdx6) plays important and complex roles in the process of inflammation, but its role in the development of rheumatoid arthritis (RA) remains unclear. Thus, we investigated the roles and mechanisms of Prdx6 in the development of arthritis in Collagen antibody-induced arthritis (CAIA) and antibody-induced arthritis (AIA) induced Prdx6 overexpressed transgenic mice as well as Prdx6 transfected RAW 264.7 cells, and macrophage isolated Prdx6 overexpressed transgenic mice and synoviocytes. Arthritis developments were induced with CAIA or AIA methods. Prdx6 transfected RAW 264.7 cells, and macrophage isolated Prdx6 overexpressed transgenic mice and synoviocytes were used for pro-inflammation responses and mechanisms. Clinical score, histopathological changes, NO generation, iNOS and COX2 expression, and NF-κB and AP-1 activities were determined in cultured macrophage and synoviocytes as well as joint tissues of mice by Western bloting, gel electromobility shift assay and histochemistry analysis. CAIA and AIA-induced arthritis development and pro-inflammation response were more exacerbated in Prdx6 overexpressed transgenic mice as well as Prdx6 transfected RAW264.7 cells, and macrophage isolated Prdx6 overexpressed transgenic mice and synoviocytes accompanied with up-regulation of JNK pathway. Moreover, JNK inhibitor completely blocked RA development and pro-inflammation responses. Our findings suggest that overexpression of Prdx6 might promote development of RA through activation of NF-κB/AP-1 coupled JNK pathway. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    07/2015; DOI:10.1002/art.39284
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    ABSTRACT: To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats.
    PLoS ONE 07/2015; 10(7):e0129664. DOI:10.1371/journal.pone.0129664 · 3.23 Impact Factor
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    ABSTRACT: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables. Epidemiologic studies showed that flavonoids also reduce the risk of colon cancer. Tectochrysin is one of the major flavonoids of Alpinia oxyphylla Miquel. However, the anti-cancer effects and the molecular mechanisms of tectochrysin in colon cancer cells have not yet been reported. We investigated whether tectochrysin could inhibit colon cancer cell growth at 1, 5, 10 μg/ml. In in vivo study, we injected a tectochrysin treatment dose of 5 mg/kg to each mouse. Tectochrysin suppressed the growth of SW480 and HCT116 human colon cancer cells. The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased. Tectochrysin treatment also inhibited activity of NF-κB. A docking model indicated that tectochrysin binds directly to the p50 unit. In in vivo, tumor weights and volumes in mice were reduced when treated with tectochrysin. Tectochrysin leads to apoptotic cell death in colon cancer cells through activation of death receptors expression via the inhibition of NF-κB. Tectochrysin can be a useful agent for the treatment of colon cancer cell growth as well as an adjuvant agent for chemo-resistant cancer cells growth.
    Molecular Cancer 06/2015; 14(1):124. DOI:10.1186/s12943-015-0377-2 · 5.40 Impact Factor
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    ABSTRACT: Accumulation of beta-amyloid and neuroinflammation trigger Alzheimer's disease. We previously found that lipopolysaccharide (LPS) caused neuroinflammation with concomitant accumulation of beta-amyloid peptides leading to memory loss. A variety of anti-inflammatory compounds inhibiting nuclear factor kappaB (NF-κB) activation have showed efficacy to hinder neuroinflammation and amyloidogenesis. We also found that bee venom (BV) inhibits NF-κB. A mouse model of LPS-induced memory loss used administration of BV (0.8 and 1.6 μg/kg/day, i.p.) to ICR mice for 7 days before injection of LPS (2.5 mg/kg/day, i.p.). Memory loss was assessed using a Morris water maze test and passive avoidance test. For in vitro study, we treated BV (0.5, 1, and 2 μg/mL) to astrocytes and microglial BV-2 cells with LPS (1 μg/mL). We found that BV inhibited LPS-induced memory loss determined by behavioral tests as well as cell death. BV also inhibited LPS-induced increases in the level of beta-amyloid (Aβ), β-and γ-secretases activities, NF-κB and its DNA-binding activity and expression of APP, and BACE1 and neuroinflammation proteins (COX-2, iNOS, GFAP and IBA-1) in the brain and cultured cells. In addition, pull-down assay and molecular modeling showed that BV binds to NF-κB. BV attenuates LPS-induced amyloidogenesis, neuroinflammation, and therefore memory loss via inhibiting NF-κB signaling pathway. Thus, BV could be useful for treatment of Alzheimer's disease.
    Journal of Neuroinflammation 06/2015; 12(1):124. DOI:10.1186/s12974-015-0344-2 · 4.90 Impact Factor
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    ABSTRACT: C-C chemokine receptor 5 (CCR5) regulates leukocyte chemotaxis and activation, and its deficiency exacerbates development of nephritis. Therefore, we investigated the role of CCR5 during lipopolysaccharide (LPS)-induced acute kidney injury. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice, both aged about 10 months, had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg). Compared with CCR5+/+ mice, CCR5-/- mice showed increased mortality and renal injury, including elevated creatinine and blood urea nitrogen levels, following LPS challenge. Compared to CCR5+/+ mice, CCR5-/- mice also exhibited greater increases in the serum concentrations of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β following LPS challenge. Furthermore, infiltration of macrophages and neutrophils, expression of intracellular adhesion molecule (ICAM)-1, and the number of apoptotic cells were more greatly increased by LPS treatment in CCR5-/- mice than in CCR5+/+ mice. The concentrations of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β were also significantly increased in the kidney of CCR5-/- mice after LPS challenge. Moreover, primary kidney cells from CCR5-/- mice showed greater increases in TNF-α production and p38 MAP kinase activation following treatment with LPS compared with that observed in the cells from CCR5+/+ mice. LPS-induced TNF-α production and apoptosis in the primary kidney cells from CCR5-/- mice were inhibited by treatment with p38 MAP kinase inhibitor. These results suggest that CCR5 deficiency increased the production of TNF-α following LPS treatment through increased activation of the p38 pathway in the kidney, resulting in renal apoptosis and leukocyte infiltration and led to exacerbation of LPS-induced acute kidney injury.
    Archives of Toxicology 06/2015; DOI:10.1007/s00204-015-1530-9 · 5.08 Impact Factor
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    ABSTRACT: Snake venom toxin (SVT) from Vipera lebetina turanica contains a mixture of different enzymes and proteins. Peroxiredoxin 6 (PRDX6) is known to be a stimulator of lung cancer cell growth. PRDX6 is a member of peroxidases, and has calcium-independent phospholipase A2 (iPLA2) activities. PRDX6 has an AP-1 binding site in its promoter region of the gene. Since AP-1 is implicated in tumor growth and PRDX6 expression, in the present study, we investigated whether SVT inhibits PRDX6, thereby preventing human lung cancer cell growth (A549 and NCI-H460) through inactivation of AP-1. A docking model study and pull down assay showed that SVT completely fits on the basic leucine zipper (bZIP) region of c-Fos of AP-1. SVT (0-10 μg/ml) inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decreased cIAP and Bcl2 expression via inactivation of AP-1. In an xenograft in vivo model, SVT (0.5 mg/kg and 1 mg/kg) also inhibited tumor growth accompanied with the reduction of PRDX6 expression, but increased expression of proapoptotic proteins. These data indicate that SVT inhibits tumor growth via inhibition of PRDX6 activity through interaction with its transcription factor AP-1.
    Oncotarget 06/2015; · 6.63 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) peptide. Evidence suggests that amyloid accumulation can be caused by oxidative stress and inflammatory responses. In this study, we examined neuroprotective effects of thiacremonone, an anti-oxidant and anti-inflammatory compound isolated from garlic. Treatment of thiacremonone significantly attenuated cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) double-mutant transgenic mice. In addition, activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) pathways in the brain was potently inhibited by thiacremonone. We also observed that thiacremonone significantly inhibited activation of NF-κB and ERK pathways induced by H2O2 and Aβ1-42 in embryonic neuronal cells. Furthermore, thiacremonone augmented peroxiredoxin 6 (PRDX6) expression in vivo and in vitro associated with reduced oxidative stress of macromolecules such as protein and lipids. This study indicates that thiacremonone might exert memory improvement via stimulating anti-oxidant system. These multiple properties could attenuate Aβ accumulation and oxidative stress in Alzheimer's brains. Thus, these results suggest that thiacremonone might be useful to intervene development or progression of neurodegeneration in AD.
    Molecular Neurobiology 05/2015; DOI:10.1007/s12035-015-9208-0 · 5.29 Impact Factor
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    ABSTRACT: Recently, biphenolic components derived from the Magnolia family have been studied for anti-cancer, anti-stress, and anti-inflammatory pharmacological effects. However, the pharmacological mechanism of action of 4-O-methylhonokiol (MH) is not clear in oral cancer. The aim of this study was to investigate the role of MH in apoptosis and its molecular mechanism in oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, as well as tumor xenografts. Here, we demonstrated that MH decreased cell growth and induced apoptosis in HN22 and HSC4 cells through the regulation of specificity protein 1 (Sp1). We employed several experimental techniques such as MTS assay, DAPI staining, PI staining, Annexin-V/7-ADD staining, RT-PCR, western blot analysis, immunocytochemistry, immunohistochemistry, TUNEL assay and in vivo xenograft model analysis. MH inhibited Sp1 protein expression and reduced Sp1 protein levels via both proteasome-dependent protein degradation and inhibition of protein synthesis in HN22 and HSC4 cells; MH did not alter Sp1 mRNA levels. We found that MH directly binds Sp1 by Sepharose 4B pull-down assay and molecular modeling. In addition treatment with MH or knocking down Sp1 expression, suppressed oral cancer cell colony formation. Moreover, MH treatment effectively inhibited tumor growth and Sp1 levels in BALB/c nude mice bearing HN22 cell xenografts. These results indicated that MH inhibited cell growth, colony formation and also induced apoptosis via Sp1 suppression in OSCC cells and xenograft tumors. Thus MH is a potent anti-cancer drug candidate for oral cancer. Copyright © 2015. Published by Elsevier Ltd.
    The international journal of biochemistry & cell biology 05/2015; 64. DOI:10.1016/j.biocel.2015.05.007 · 4.24 Impact Factor
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    ABSTRACT: Objectives This study aimed to investigate the beneficial effects of Cheonggukjang (CGK) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on neurotoxic damages. Methods The specific aspects of brain functions were measured in ICR mice that had been pretreated for 4 weeks with three difference doses of CGK before trimethyltin (TMT) treatment. Results The short- and long-term memory loss induced by TMT treatment was significantly improved in the CGK-pretreated group in a dose-dependent manner. The number of dead cells in the granule cell layer of the dentate gyrus was decreased in the TMT/CGK-cotreated group relative to the TMT/vehicle-treated group, whereas significant suppression of acetylcholinesterase (AChE) activity was observed in the same group. Additionally, a dose-dependent increase in nerve growth factor (NGF) concentration, activation of the NGF receptor signaling pathway including the TrkA high affinity receptor and p75(NTR) low affinity receptor, and decline in Bax/Bcl-2 level was measured in all TMT/CGK-treated groups, although a decrease in the active form of caspase-3 was observed in the TMT/H-CGK-treated group. Furthermore, superoxide dismutase (SOD) activity was enhanced in the TMT/CGK-treated group, whereas the level of malondialdehyde (MDA), a marker of lipid peroxidation, was 43-58% lower in the TMT/CGK-treated group than the TMT/vehicle-treated group. Discussion These results demonstrate that CGK fermented by mixed culture of B. subtilis and L. sakei could exert a wide range of beneficial activities for neurodegenerative diseases, including Alzheimer, Parkinson, and Huntington disease.
    Nutritional Neuroscience 04/2015; DOI:10.1179/1476830515Y.0000000025 · 2.11 Impact Factor
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    ABSTRACT: Inflammation is associated with cancer-prone microenvironment, leading to cancer. IL-32 is expressed in chronic inflammation-linked human cancers. To investigate IL-32α in inflammation-linked colorectal carcinogenesis, we generated a strain of mice, expressing IL-32 (IL-32α-Tg). In IL-32α-Tg mice, azoxymethane (AOM)-induced colon cancer incidence was decreased, whereas expression of TNFR1 and TNFR1-medicated apoptosis was increased. Also, IL-32α increased ROS production to induce prolonged JNK activation. In colon cancer patients, IL-32α and TNFR1 were increased. These findings indicate that IL-32α suppressed colon cancer development by promoting the death signaling of TNFR1.
    Oncotarget 04/2015; · 6.63 Impact Factor
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    ABSTRACT: Naphthofuran compounds have been known to regulate HNF 4α which is associated with proliferation, progression and metastasis of HCC. In this study, we investigated whether N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide (NHDC), a novel synthetic naphthofuran compound inhibits liver tumor growth through activation of HNF 4α. Treatment with different concentrations (1-10.8 µM) of NHDC for various periods (0-72 h) inhibited liver cancer cells (HepG2, Hep3B) growth as well as colony formation followed by induction of apoptosis in a concentration dependent manner. NHDC also induced expression of the apoptosis regulating genes as well as inhibiting the action of STAT3. These inhibitory effects were associated with enhancement of expression and DNA binding activity of HNF 4α. In vivo study confirmed that liver tumor growth was prevented with NHDC (5 mg/kg), and its effect was also related with inhibition of STAT3 pathway through enhancement of expression and DNA binding activity of HNF 4α. Moreover, siRNA of HNF 4α abolished NHDC-induced cell growth inhibition as well as DNA binding activity and phosphorylation of STAT3. Pull down assay docking prediction analysis proved that NHDC directly binds to hydrophobic fatty acid ligand binding site of HNF 4α. A novel naphthofuran compound, NHDC inhibited liver tumor growth by inactivating of STAT3 through direct biding to HNF 4α. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 04/2015; DOI:10.1002/mc.22311 · 4.77 Impact Factor
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    Ji Sung Kim · Yong Guk Kim · Minji Pyo · Hong Kyung Lee · Jin Tae Hong · Youngsoo Kim · Sang-Bae Han
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    ABSTRACT: Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.
    Immune Network 04/2015; 15(2):58-65. DOI:10.4110/in.2015.15.2.58
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    ABSTRACT: Two active substances from ginseng fermented using Ganoderma lucidum mycelia were investigated for antiproliferative effects against the human lung cancer cell line A549. The chloroform fraction of fermented ginseng extracts showed a strong antiproliferative effect. This fraction was isolated and purified using silica gel and C18 resin column chromatography and semi-preparative reverse phase HPLC. The structures of isolated compounds were determined using spectroscopic methods (ESI-MS, 1H and 13C NMR). Isolated compounds were identified as ginsenoside compound K and 3-oxo-compound K. Both inhibited A549 cell growth in a dose-dependent manner. Cell viability values for ginsenoside compound K were 74.88, 59.30, 5.76, 5.79, and 6.27% at 6.25, 12.50, 25.00, 50.00, and 100.00 μg/mL, respectively, and ginsenoside 3-oxo-compound K showed values 89.40, 59.62, 6.05, and 4.64% at 3.70, 7.50, 15.00, and 30.00 μg/mL, respectively. Compound K and 3-oxo-compound K from fermented ginseng can be used as natural anti-cancer agents.
    Food science and biotechnology 04/2015; 24(2):567-574. DOI:10.1007/s10068-015-0074-3 · 0.66 Impact Factor
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    ABSTRACT: Activation of nuclear factor kappa-B (NF-κB) is implicated in drug resistant of lung cancer cells. Our previous data showed that thiacremonone inhibited activation of NF-κB. In the present study, we investigated whether thiacremonone enhanced susceptibility of lung cancer cells to a common anti-cancer drug paclitaxel by further inhibition of NF-κB. Thus, we used the threefold lower doses of IC50 values (50 μg/ml thiacremonone and 2.5 nM paclitaxel). We found that combination treatment with thiacremonone and paclitaxel was more susceptible (combination index; 0.40 in NCI-H460 cells and 0.46 in A549 cells) in cell growth inhibition of two types of lung cancer cell lines compared to a single agent treatment. Consistent with the combination effect on cancer cell growth inhibition, the combination treatment further induced apoptotic cell death and arrested the cancer cells in G2/M phase accompanied with a much lower expression of cdc2 and cyclin B1, and inhibited colony formation. Much more inactivation of NF-κB and greater expression of NF-κB target apoptosis regulated genes such as caspase-8 and PARPs were found by the combination treatment. Molecular model and pull down assay as well as MALDI-TOF analysis demonstrated that thiacremonone directly binds to p50. These data indicated that thiacremonone leads to increased apoptotic cell death in lung cancer cell lines through greater inhibition of NF-κB by the combination treatment with paclitaxel.
    Archives of Pharmacal Research 03/2015; 38(7). DOI:10.1007/s12272-015-0589-4 · 1.75 Impact Factor
  • Hwa Sun Ryu · Hong Kyung Lee · Ji Sung Kim · Yong Guk Kim · Minji Pyo · Jieun Yun · Bang Yeon Hwang · Jin Tae Hong · Youngsoo Kim · Sang-Bae Han
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    ABSTRACT: Saururus chinensis is a medicinal plant used to treat jaundice, pneumonia, edema, fever, and several inflammatory diseases. Saucerneol D (SD), a lignan constituent of this plant, has antioxidant, anti-asthmatic, and anti-inflammatory activities. SD has been previously reported to inhibit the pro-inflammatory responses of RAW264.7 cells and primary mast cells. In this study, we investigated the effect of SD on the functions of dendritic cells (DCs). SD was isolated from methanol extract of the roots of S. chinensis. Bone marrow-derived DCs were used as target cells. The effects of SD on the following DC functions were examined: surface molecule expression, cytokine expression, migration, allogenic T cell activation, heme oxygenase-1 expression, and Toll-like receptor 4 signaling. In lipopolysaccharide (LPS)-treated DCs, SD inhibited the expression of cell surface molecules (MHC I/II, CD40, CD80, and CD86), the production of inflammatory mediators (nitric oxide, IL-12, IL-1β, and TNF-α), and allogenic T cell activation capacity. SD also inhibited DC migration toward MIP-3β by down-regulating CCR7 expression. SD attenuated LPS-induced activation of NF-κB and MAPK signaling in DCs, but did not directly inhibit kinase activities of IRAK1, IRAK4, TAK1, or IKKβ in enzymatic assays. SD did not inhibit LPS binding to myeloid differentiation protein-2, co-receptor of TLR4. SD increased the production of reactive oxygen species, Nrf-2, and heme oxygenase (HO)-1, which degrades the heme to immunosuppressive carbon monoxide and biliverdin, which may underlie the anti-inflammatory effects in SD-treated DCs. Taken together, these data suggest that SD suppresses LPS-induced activation of DCs through the induction of HO-1, but not by directly affecting Toll-like receptor 4 signaling. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Journal of ethnopharmacology 03/2015; 166. DOI:10.1016/j.jep.2015.03.020 · 2.94 Impact Factor
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    ABSTRACT: Background and purpose cAMP as a second messenger stimulates expression of microphthalmia-associated transcription factor (MITF) or tyrosinase gene under ultraviolet B (UVB)-induced skin pigmentation. Diphenylmethylene hydrazinecarbothioamide (QNT 3-80) inhibits α-melanocyte-stimulating hormone (α-MSH)-induced melanin production in B16 murine melanoma cells but its molecular basis remains to be defined. Here, we investigated an antimelanogenic mechanism of QNT 3-80 in the amelioration of skin hyperpigmentation. Experimental approach cAMP-elevated melanocyte cultures were used for in vitro assays and UVB-irradiated dorsal skins of guinea pigs for in vivo pigmentation. Immunoprecipitation, kemptide phosphorylation, fluorescence analysis and docking simulation were applied to elucidate a molecular mechanism of QNT 3-80. Key results QNT 3-80 inhibited melanin production in vitro under cAMP-elevated melanocyte cultures including those from human foreskins, and also ameliorated hyperpigmentation in vivo under UVB-irradiated dorsal skins of guinea pigs. As a mechanism, QNT 3-80 directly antagonized cAMP binding to the regulatory subunit of protein kinase A (PKA), nullified the dissociation and activation of inactive PKA holoenzyme in melanocytes, and fitted into the cAMP-binding site on the crystal structure of human PKA under the most energetically favorable simulation. QNT 3-80 consequently inhibited cAMP- or UVB-induced phosphorylation (activation) of cAMP-responsive element (CRE)-binding protein (CREB) in vitro and in vivo, thus down-regulating expression of MITF or tyrosinase gene in the melanogenic process. Conclusions and Implications Taken together, this study suggests a significant implication of QNT 3-80 in the treatment of skin disorders with hyperpigmented patches via the cAMP-binding site of PKA as a molecular target. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 03/2015; 172(13). DOI:10.1111/bph.13134 · 4.99 Impact Factor
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    ABSTRACT: Two new iridoids, 6-O-[(E)-feruloyl]jioglutin D (1) and 6-O-(4-hydroxybenzoyl)jioglutin D (2), and six known compounds, minecoside (3), specioside (4), picroside II (5), picroside III (6), 4-hydroxybenzoic acid (7), and martynoside (8), were isolated from the stem of Catalpa ovata. The structures of the new compounds were established on the basis of spectroscopic techniques, including 1D- and 2D-NMR.
    Helvetica Chimica Acta 03/2015; 98(3). DOI:10.1002/hlca.201400203 · 1.39 Impact Factor
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    Zhenzhen Hu · Eun-Hye Oh · Yeon Bok Chung · Jin Tae Hong · Ki-Wan Oh
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    ABSTRACT: The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the 3(rd) day. CART peptides were over-expressed on the 5(th) day in the striata of behaviorally sensitized mice. A higher proportion of CART(+) cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both D1R and D2R antagonists, SCH 23390 (D1R selective) and raclopride (D2R selective), blocked cocaine induced-behavioral sensitization, CART over-expression, and cyclic adenosine 5'-monophosphate (cAMP)/protein kinase A (PKA)/phospho-cAMP response element-binding protein (pCREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, pCREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both D1R and D2R knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/pCREB signal pathways were inhibited in the D1R-KO mice, but not in the D2R-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/pCREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by D1R.
    Korean Journal of Physiology and Pharmacology 03/2015; 19(2):89-97. DOI:10.4196/kjpp.2015.19.2.89 · 1.26 Impact Factor
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    ABSTRACT: Objective Chronic excessive food intake leads to energy imbalance, resulting in hepatic steatosis and inflammation. Interleukin-32 (IL-32) is known to be a pro-inflammatory cytokine associated with chronic inflammation and cancer. Therefore, the relationship between IL-32 and chronic excessive food intake-induced liver disease was investigated.Methods Male IL-32β transgenic and wild-type mice were fed a high-fat diet (HFD) for 15 weeks. They were compared with wild-type mice on a standard chow diet. Daily food intake, body and liver weight, serum biochemistry, histopathological analysis of the liver, and hepatic immune response were determined.ResultsIL-32β mice on HFD showed lower lipid accumulation, reduced infiltration of immune cells, and lower production of pro-inflammatory cytokines in the liver. The expression of the peroxisome proliferator-activated receptor γ (PPARγ) was downregulated and the adenosine 50-monophosphate (AMP)-activated protein kinase (AMPK) was activated in the liver of IL-32β mice compared to wild-type mice. Furthermore, IL-32β over-expression activated the AMPK pathway and IL-32β downregulation inactivated the AMPK pathway in HepG2 cells under high-glucose conditions.Conclusions These data suggest that IL-32β modulates lipid accumulation through inhibition of PPARγ expression and AMPK activation.
    Obesity 02/2015; 23(3). DOI:10.1002/oby.21001 · 4.39 Impact Factor

Publication Stats

4k Citations
932.49 Total Impact Points

Institutions

  • 2015
    • Chonnam National University
      • School of Dentistry
      Gwangju, Gwangju, South Korea
  • 1998–2015
    • Chungbuk National University
      • College of Pharmacy
      Chinsen, Chungcheongbuk-do, South Korea
  • 2008–2012
    • Konkuk University
      • • Department of Bioscience and Technology
      • • Bio/Molecular Informatics Center
      Sŏul, Seoul, South Korea
    • Safety Research Institute
      Georgia, United States
  • 1998–2011
    • Korea Food and Drug Administration
      Seishō-gun, North Gyeongsang, South Korea
  • 2006
    • Soonchunhyang University
      Onyang, Chungcheongnam-do, South Korea
  • 2003
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • Laboratory of Cellular Biology
      Ansan, Gyeonggi, South Korea
    • Ewha Womans University
      Sŏul, Seoul, South Korea
  • 1993
    • Korea Institute of Toxicology
      Sŏul, Seoul, South Korea