Myung Koo Lee

Chungbuk National University, Chinsen, Chungcheongbuk-do, South Korea

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Publications (102)243.48 Total impact

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    ABSTRACT: Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30 min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina.
    No preview · Article · Dec 2015 · Neuroscience Letters
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    ABSTRACT: Prion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrPC) to the pathogenic form, PrPSc. Compounds that inhibit this process by blocking conversion to the PrPSc could provide useful anti-prion therapies. However, no suitable drugs have been identified to date. To identify novel anti-prion compounds, we developed a combined structure- and ligand-based virtual screening system in silico. Virtual screening of a 700,000-compound database, followed by cluster analysis, identified 37 compounds with strong interactions with essential hotspot PrP residues identified in a previous study of PrPC interaction with a known anti-prion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays, and surface plasmon resonance. Some compounds effectively reduced PrPSc levels and one of these compounds also showed a high binding affinity for PrPC. These results provide a promising starting point for the development of anti-prion compounds.
    Full-text · Article · Nov 2015 · Scientific Reports
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    ABSTRACT: The 14-3-3 protein has been used as a biomarker for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, weakly positive 14-3-3 leads to false positive results and an incorrect diagnosis. We attempted to use quantitative data for tau protein to provide an accurate diagnosis based on weak 14-3-3 protein. Sixty-two patients with sCJD, including pathologically confirmed, clinically definite, and probable cases, and 89 non-CJD patients were investigated based on a Korean population. Among them, 20 sCJD and 14 non-CJD showed weakly positive 14-3-3. The total tau (t-tau) and phosphorylated tau (p-tau) protein levels were measured by ELISA, and the p-tau to t-tau ratio (p/t ratio) was calculated. The combined use of the 14-3-3 protein assay, t-tau levels, and p/t ratio improved the specificity of diagnosis compared with the use of the 14-3-3 protein assay alone (47% for 14-3-3 alone; 85.94% for 14-3-3 combined with t-tau; 90.62% for 14-3-3 combined with the p/t ratio). In addition, 18 of 20 sCJD and 12 of 14 non-CJD who were weakly positive for 14-3-3 were positive for the p/t ratio and negative for the p/t ratio, respectively. When used in combination with the 14-3-3 protein, the tau protein is useful as a biomarker for the precise diagnosis of sCJD.
    No preview · Article · Oct 2015 · Scientific Reports
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    ABSTRACT: Background: Ethanol extract from Gynostemma pentaphyllum (GP) shows anti-stress and anxiolytic functions in mice, and also protects dopamine neurons in 6-hydroxydopamine-lesioned rat model of Parkinson's disease. In addition, gypenosides (the gypenoside-enriched components of GP, GPS) have a protective effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. In this study, the ameliorating effects of GPS on chronic stress-induced anxiety disorders in mice were investigated. Methods: Mice were orally treated with GPS (100 and 200 mg/kg) once a day for 10 days, followed by exposure to electric footshock (EF) stress (0.6 mA, 1 s every 5 s, 3 min). After the final administration of either GPS, water extract of GP (GP-WX) or ethanol extract of GP (GP-EX, positive control), the behavioral tests such as elevated plus-maze, marble burying and locomotor activity tests, and the biochemical parameters including dopamine, serotonin and corticosterone levels, and c-Fos expression were examined. Results: Treatment with GPS (100 and 200 mg/kg) increased the number of open arm entries and the time spent on open arms in elevated plus-maze which were reduced by chronic EF stress. GPS (100 and 200 mg/kg) reduced the number of marbles buried which increased by chronic EF stress. In these states, the brain levels of dopamine and serotonin decreased by chronic EF stress and they were recovered by GPS. The serum levels of corticosterone increased by chronic EF stress were also reduced by GPS (100 and 200 mg/kg). Finally, chronic EF stress-induced c-Fos expression was markedly reduced by GPS (100 and 200 mg/kg) in the brain. GPS (100 and 200 mg/kg) also showed an equivalent efficacy on anxiolytic functions, as compared with GP-EX (50 mg/kg). However, GP-WX (50 mg/kg) showed a less effect on anxiety disorders than GP-EX (50 mg/kg) and GPS (100 and 200 mg/kg). Conclusion: These results suggest that GPS (100 and 200 mg/kg) has anxiolytic effects on chronic EF stress-induced anxiety disorders by modulating dopamine and serotonin neuronal activities, c-Fos expression and corticosterone levels. GPS may serve as a phytonutrient in chronic stress-induced anxiety disorders.
    Preview · Article · Sep 2015 · BMC Complementary and Alternative Medicine
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    ABSTRACT: L-DOPA causes neurotoxicity by modulating the Epac-ERK system in PC12 cells. This study investigated the effects of a single treatment with L-DOPA and multiple treatments with L-DOPA (MT-LD) on ERK1/2 and JNK1/2-c-Jun systems. In PC12 cells, a toxic L-DOPA concentration (200 μM) induced sustained ERK1/2 and JNK1/2 phosphorylation that was inhibited by the Epac inhibitor brefeldin A, but not by the PKA inhibitor H89. This ERK1/2 and JNK1/2 phosphorylation was also inhibited by ERK1/2 (U0126) and JNK1/2 (SP600125) inhibitors, respectively, but sustained ERK1/2 phosphorylation was not affected by JNK1/2 phosphorylation. A non-toxic L-DOPA concentration (20 μM) induced c-Jun phosphorylation (Ser73) via transient ERK1/2 phosphorylation, whereas the toxic L-DOPA concentration induced c-Jun phosphorylation (Ser63) and c-Jun expression via Epac-sustained ERK1/2-JNK1/2 phosphorylation, which then enhanced cleaved caspase-3 expression. MT-LD (20 μM) initially enhanced c-Jun phosphorylation (Ser73) (for 1-4 days), but later (5-6 days) induced c-Jun phosphorylation (Ser63) and c-Jun expression. In the 6-hydroxydopamine-lesioned rat model of Parkinson's disease, L-DOPA administration (10 mg/kg) protected against neurotoxicity through c-Jun phosphorylation (Ser73) for 1-2 weeks. However, L-DOPA administration (10 or 30 mg/kg) showed neurotoxicity through c-Jun phosphorylation (Ser63) and c-Jun expression via ERK1/2 phosphorylation for 3-4 weeks. Thus, in PC12 cells, non-toxic L-DOPA treatment maintained cell survival through c-Jun phosphorylation (Ser73). By contrast, toxic L-DOPA treatment or MT-LD (20 μM) induced c-Jun phosphorylation (Ser63) and c-Jun expression via Epac-dependent sustained ERK1/2 and JNK1/2 phosphorylation, which subsequently led to cell death. These results were validated by those obtained after long-term L-DOPA administration in a rat model of Parkinson's disease. Our data indicate that L-DOPA causes neurotoxicity via the ERK1/2-c-Jun system in dopaminergic neuronal cells.
    No preview · Article · Sep 2015 · Neuropharmacology
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    ABSTRACT: Gypenosides (GPS) and ethanol extract of Gynostemma pentaphyllum (GP-EX) shows anxiolytic effects on affective disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD). Long-term administration of L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of severe motor side effects such as L-DOPA-induced-dyskinesia (LID) in PD. The present study investigated the effects of GPS and GP-EX on LID in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Daily administration of L-DOPA (25 mg/kg) in the 6-OHDA-lesioned rat model of PD for 22 days induced expression of LID, which was determined by the body and locomotive AIMs scores and contralateral rotational behaviors. However, co-treatments of GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg) with L-DOPA significantly attenuated the development of LID without compromising the anti-parkinsonian effects of L-DOPA. In addition, the increases in ∆FosB expression and ERK1/2 phosphorylation in 6-OHDA-lesioned rats induced by L-DOPA administration were significantly reduced by co-treatment with GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg). These results suggest that GPS (25 and 50 mg/kg) and GP-EX (50 mg/kg) effectively attenuate the development of LID by modulating the biomarker activities of ∆FosB expression and ERK1/2 phosphorylation in the 6-OHDA-lesioned rat model of PD. GPS and GP-EX will be useful adjuvant therapeutics for LID in PD.
    Preview · Article · Apr 2015 · BMC Neuroscience
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    ABSTRACT: Five new dammarane-type saponins, gypenosides GD1-GD5 (1-5), along with six known saponins (6-11), were isolated from the aerial parts of Gynostemma pentaphyllum using various chromatographic methods. Their structures were elucidated by a combination of spectroscopic and spectrometric data, including 1D and 2D NMR and HRESIMS. All isolates were tested for their inhibitory effects on IL-6-induced STAT3 promoter activity in Hep3B cells. Compounds 1, 9, and 11 displayed potent inhibitory effects, with IC50 values ranging from 0.27 to 0.59 μM.
    No preview · Article · Apr 2015 · Journal of Natural Products
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    ABSTRACT: The present study investigated the effects of (-)-sesamin on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using PC12 cells and dopaminergic neuronal cells of 6-OHDA-lesioned rat model of Parkinson's disease (PD). In PC12 cells, treatment with (-)-sesamin (25 µM) reduced 6-OHDA (100 µM)-induced cell death and induced transient extracellular signal-regulated kinase (ERK1/2) phosphorylation and Bad phosphorylation at Ser112 (BadSer112). In contrast, sustained ERK1/2 phosphorylation, p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK1/2) phosphorylation, and cleaved-caspase-3 activity, all of which were induced by 6-OHDA (100 µM), were inhibited by treatment with (-)-sesamin (25 µM). Furthermore, co-treatment with (-)-sesamin (30 mg/kg, p.o.) once a day for 28 days significantly increased the number of tyrosine hydroxylase-immunopositive neuronal cells and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the substantia nigra-striatum of 6-OHDA-lesioned rat model of PD with or without L-DOPA treatment. These results suggest that (-)-sesamin protects 6-OHDA-induced cytotoxicity via the activation of transient ERK1/2-BadSer112 system and the inhibition of sustained ERK-p38MAPK-JNK1/2-caspase-3 system in PC12 cells. (-)-Sesamin also shows protective effects on long-term L-DOPA therapy in dopaminergic neuronal cells of PD rat models. (-)-Sesamin may serve as adjuvant therapeutics in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Mar 2015 · Neurochemistry International
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    ABSTRACT: Multiple treatments with L-3,4-dihydroxyphenylalanine (L-DOPA; 20 µM) induce neurite-like outgrowth and reduce dopamine biosynthesis in rat adrenal pheochromocytoma (PC) 12 cells. We therefore investigated the effects of multiple treatments with L-DOPA (MT-LD) on cell survival and death over a duration of 6 days by using PC12 cells and embryonic rat midbrain primary cell cultures. MT-LD (10 and 20 µM) decreased cell viability, and both types of cells advanced to the differentiation process at 4–6 days. MT-LD induced cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) phosphorylation and exchange protein activation by cAMP (Epac) expression at 1–3 days, which led to transient extracellular signal-regulated kinase (ERK1/2) phosphorylation in both cells. In these states, MT-LD activated cAMP-response element binding protein (CREB; Ser133) and tyrosine hydroxylase (Ser40) phosphorylation in PC12 cells, which led to an increase in intracellular dopamine levels. In contrast, MT-LD induced prolonged Epac expression at 4–5 days in both cells, which led to sustained ERK1/2 phosphorylation. In these states, the dopamine levels were decreased in PC12 cells. In addition, MT-LD induced c-Jun N-terminal kinase1/2 phosphorylation and cleaved caspase-3 expression at 4–6 days in both cells. These results suggest that MT-LD maintains cell survival via PKA-transient ERK1/2 activation, which stimulates dopamine biosynthesis. In contrast, at the later time period, MT-LD induces differentiation via both prolonged Epac and sustained ERK1/2 activation, which subsequently leads to the cell death process. Our data demonstrate that L-DOPA can cause neurotoxicity by modulating the Epac-ERK pathways in neuronal and PC12 cells. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Dec 2014 · Journal of Neuroscience Research
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    ABSTRACT: Gintonin is a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin elicits an intracellular calcium concentration [Ca(2+)]i transient via activation of LPA receptors and regulates calcium-dependent ion channels and receptors. [Ca(2+)]i elevation by neurotransmitters or depolarization is usually coupled to neurotransmitter release in neuronal cells. Little is known about whether gintonin-mediated [Ca(2+)]i transients are also coupled to neurotransmitter release. The PC12 cell line is derived from a pheochromocytoma of the rat adrenal medulla and is widely used as a model for catecholamine release. In the present study, we examined the effects of gintonin on dopamine release in PC12 cells. Application of gintonin to PC12 cells induced [Ca(2+)]i transients in concentration-dependent and reversible manners. However, ginsenoside Rg3, another active ingredient of ginseng, induced a lagged and irreversible [Ca(2+)]i increase. The induction of gintonin-mediated [Ca(2+)]i transients was attenuated or blocked by the LPA1/3 receptor antagonist Ki16425, a phospholipase C inhibitor, an inositol 1,4,5-triphosphate receptor antagonist, and an intracellular Ca(2+) chelator. Repeated treatment with gintonin induced homologous desensitization of [Ca(2+)]i transients. Gintonin treatment in PC12 cells increased the release of dopamine in a concentration-dependent manner. Intraperitoneal administration of gintonin to mice also increased serum dopamine concentrations. The present study shows that gintonin-mediated [Ca(2+)]i transients are coupled to dopamine release via LPA receptor activation. Finally, gintonin-mediated [Ca(2+)]i transients and dopamine release via LPA receptor activation might explain one mechanism of gintonin-mediated inter-neuronal modulation in the nervous system. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Nov 2014 · Neuroscience Letters
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    ABSTRACT: Ethanol extract (GP-EX) of Gynostemma pentaphyllum (GP) ameliorates chronic stress-induced anxiety in mice. The present study investigated the effects of gypenoside-enriched components (GPS), GP-EX and water extract of GP (GP-WX) on MPTP lesion-induced affective disorders in C57BL/6 mice. GPS (50mg/kg) and GP-EX (50mg/kg) for 21 day-treatment period improved the symptom of anxiety disorders in MPTP-lesioned mouse model of PD with or without L-DOPA treatment, which was examined by the elevated plus-maze and marble burying tests. In these states, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) significantly increased the brain levels of dopamine and serotonin in MPTP-lesioned mouse model of PD with or without L-DOPA treatment. In addition, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) showed protective effects on dopaminergic neurons in MPTP-lesioned mouse model of PD with or without L-DOPA treatment. In contrast, GPS (30mg/kg) and GP-WX (50mg/kg) showed anxiolytic effects in the same animal models, but it was not significant. These results suggest that GPS (50mg/kg) and GP-EX (50mg/kg) showed anxiolytic effects on affective disorders and protective effects on dopaminergic neurons by modulating the brain levels of dopamine and serotonin in MPTP-lesioned mouse model of PD with or without L-DOPA treatment. Clinical trials of GPS and GP-EX need to be conducted further so as to develop adjuvant therapeutic agents for PD patients.
    No preview · Article · Apr 2014 · Brain research
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    ABSTRACT: The roles of cyclic AMP (cAMP)-ERK-Bad signaling pathways in 6-hydroxydopamine (6-OHDA)-induced cell survival and death were investigated. In PC12 cells, 6-OHDA (10-100 μM) concentration-dependently increased the intracellular levels of cAMP mediated by the Ca(2+)-CaMKII-adenylyl cyclase system. 6-OHDA at the non-toxic level (10 μM) induced transient ERK1/2 phosphorylation and BadSer112 phosphorylation, which maintained cell survival. In contrast, the high levels of cAMP induced by toxic levels (50 and 100 μM) of 6-OHDA induced sustained ERK1/2 phosphorylaton and BadSer155 phosphorylation. The cells then moved to cell death process through Bcl2 phosphorylation and caspase-3 activation. BadSer155 phosphorylation by 6-OHDA was inhibited by PKA (H89) and MEK (U0126) inhibitors, indicating that it was mediated via the cAMP-PKA-sustained ERK1/2 system. In SK-N-BE(2)C cells, the non-toxic level of 6-OHDA also showed transient ERK1/2 phosphorylation and BadSer112 phosphorylation, and toxic levels of 6-OHDA exhibited sustained ERK1/2 phosphorylation and BadSer155 phosphorylation. These results suggest that ERK1/2 phosphorylation by 6-OHDA shows biphasic functions on cell survival and death in PC12 cells. It is, therefore, proposed that the cAMP-ERK1/2-Bad signaling pathways incurred by toxic levels of 6-OHDA play a role in dopamine neuron death of animal models of Parkinson's disease.
    No preview · Article · Sep 2013 · Toxicology in Vitro
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    ABSTRACT: Three new diterpenes (7, 15 and 17) and two new neolignans (19 and 20) along with nineteen known compounds have been isolated from the fruits of Vitex rotundifolia. Their structures were elucidated by a combination of 1D and 2D NMR, HRESI-MS, and CD data. All isolates were tested for their inhibitory activities on LPS-induced nitric oxide production in RAW264.7 cells. Of these, compounds 3, 4, 7, 13, 15, 19, and 24 found to inhibit nitric oxide production with the IC50 values ranging from 11.3 to 24.5μM.
    No preview · Article · Aug 2013 · Bioorganic & medicinal chemistry letters
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    ABSTRACT: We investigated the antioxidant, nitrite scavenging, immune-enhancing and antimicrobial effects of the Lentinus edodes fruiting body extracts (LEFB extract) cultivated in the solid state using corn cob. The CAT, SOD and GSH-Px activities in the LEFB extract (400mg)-fed group were approximately 1.70, 1.64, and 2.2 times higher than those of the control group. The nitrite scavenging activity was highest (86.4%) when the LEFB extract concentration was 600 μg/mL. The immune-enhancing and antimicrobial effects of LEFB extract after an experimental Bordetella bronchiseptica infection were examined. White blood and neutrophil in the LEFB extract (400 mg)-fed group were approximately 2.1 and 2.2 times higher, respectively, than those of the control group. The total leukocyte was 30% higher than that of the control group. The CD4: CD8 ratio in the LEFB extract (200 mg)-fed group was increased approximately 54.3% compared to that of the control group. The levels of TNF-α and IFN-γ mRNA expression in the LEFB extract (400 mg)-fed group were approximately 49 and 50% lower than those of the control group. The bacteria and inflammatory cell in the LEFB extract (400 mg)-fed group were approximately 48.7 and 29% lower, respectively, than that of the control group. These results suggest that the LEFB extract may be useful in immune function improvement.
    No preview · Article · Apr 2013 · Korean Journal of Chemical Engineering
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    ABSTRACT: In this study, the effects of herbal ethanol extracts of Gynostemma pentaphyllum (GP-EX), on chronic electric footshock (EF) stress-induced anxiety disorders were investigated in mice, which were orally treated with GP-EX (30 mg/kg and 50 mg/kg) once a day for 14 days, followed by exposure to EF stress (2 mA, with an interval and duration of 10 s for 3 min). After the final exposure to EF stress, the elevated plus-maze and marble burying tests were performed, and the levels of dopamine and serotonin in the brain, the serum levels of corticosterone, and the expression of c-Fos in the paraventricular nuclei (PVN) were determined. Treatment with GP-EX (30 mg/kg and 50 mg/kg) significantly recovered the number of entries into open arms and time spent on open arms, which was reduced by chronic EF stress. GP-EX (30 mg/kg and 50 mg/kg) also reduced the number of marbles buried, which was increased by chronic EF stress. In addition, electric EF stress significantly decreased the levels of dopamine and serotonin in the brain, which was recovered by treatment with GP-EX (30 mg/kg and 50 mg/kg). The serum levels of corticosterone, which were markedly increased by chronic EF stress, were reduced by treatment with GP-EX (30 mg/kg and 50 mg/kg). Chronic EF stress-induced increases in c-Fos expression were also markedly reduced by GP-EX (30 mg/kg and 50 mg/kg) in the PVN. These results suggest that GP-EX shows anxiolytic functions, determined by the elevated plus-maze and marble burying tests, which are mediated by modulating the activity of dopamine and serotonin neurons as well as the expression of c-Fos in the brain, and the serum levels of corticosterone. Clinical trials of herbal GP-EX and its bioactive components need further investigation.
    Preview · Article · Apr 2013 · Molecules
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    ABSTRACT: The effects of berberine on long-term administration of L-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) were investigated. Rat models of PD were prepared by 6-OHDA lesions in the ipsilateral sides, and then were treated with berberine (5 and 15 mg/kg) and/or L-DOPA (10 mg/kg) once daily for 21 days. Treatments with either concentration of berberine (5 and 15 mg/kg) in 6-OHDA-lesioned groups decreased the numbers of tyrosine hydroxylase (TH)-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum as compared to 6-OHDA-lesioned groups. In addition, dopaminergic neuronal cell death of the ipsilateral sides in 6-OHDA-lesioned groups was attenuated by L-DOPA administration. However, both concentrations of berberine in 6-OHDA-lesioned groups treated with L-DOPA aggravated the numbers of TH-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, DOPAC and HVA in the striatum as compared to rats not treated with berberine. These results suggest that berberine leads to the degeneration of dopaminergic neuronal cells in the substantia nigra in the rat model of PD with chronic L-DOPA administration. Long-term L-DOPA therapy that may involve possibly neurotoxic isoquinoline agents including berberine should involve monitoring for adverse symptoms.
    No preview · Article · Mar 2013 · Archives of Pharmacal Research
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    ABSTRACT: We demonstrated that ombuin-3-O- β-D-glucopyranoside (ombuine), a flavonoid from Gynostemma pentaphyllum, is a dual agonist for peroxisome proliferator-activated receptors (PPARs) α and δ/ β. Using surface plasmon resonance (SPR), time-resolved fluorescence resonance energy transfer (FRET) analyses, and reporter gene assays, we showed that ombuine bound directly to PPARα and δ/ βbut not to PPARγ or liver X receptors (LXRs). Cultured HepG2 hepatocytes stimulated with ombuine significantly reduced intracellular concentrations of triglyceride and cholesterol and downregulated the expression of lipogenic genes, including sterol regulatory element binding protein-1c (SREBP1c) and stearoyl-CoA desaturase-1 (SCD-1), with activation of PPARα and δ/ β. Activation of LXRs by ombuine was confirmed by reporter gene assays, however, SPR and cell-based FRET assays showed no direct binding of ombuine to either of the LXRs suggesting LXR activation by ombuine may be operated via PPARα stimulation. Ombuine-stimulated macrophages showed significantly induced transcription of ATP binding cassette cholesterol transporter A1 (ABCA1) and G1 (ABCG1), the key genes in reverse cholesterol transport, which led to reduced cellular cholesterol concentrations. These results suggest that ombuine is a dual PPAR ligand for PPAR α and δ/ βwith the ability to decrease lipid concentrations by reducing lipogenic gene expression in hepatocytes and inducing genes involved in cholesterol efflux in macrophages.
    Full-text · Article · Dec 2012 · Biochemical and Biophysical Research Communications
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    ABSTRACT: The immunomodulatory effects of the ethanol extract of Gynostemma pentaphyllum (GP-EX) were examined in electric footshock (EFS)-stressed mice. The mice were orally administered various doses of GP-EX for 7 days before exposure to EFS (duration: 3 min, interval: 10 s, intensity: 2 mA) once a day from day 8 for 14 days with continuous daily feeding of GP-EX. Oral administration of GP-EX to mice prevented EFS stress-induced immunosuppression as determined by the lymphoid organ (thymus and spleen) weight and cellularity. In addition, oral administration of GP-EX restored EFS-suppressed functional properties of mature lymphocytes in terms of concanavalin A-induced proliferation of splenocytes and lipopolysaccharide-induced cytokine production (TNF-α, IL-1β). Furthermore, we found that mice that were orally administered with GP-EX generated much more potent ovalbumin-specific cytotoxic T lymphocyte responses upon intravenous ovalbumin injection compared to the untreated controls. These results demonstrate that oral administration of the ethanol extract of Gynostemma pentaphyllum could increase host defense in immunocompromised situations such as stress-induced immunosuppression.
    Full-text · Article · Dec 2012 · Molecules
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    ABSTRACT: We investigated the effects of the antioxidant and the nitrite scavenging activities of the extracts from Pleurotus ferulae fruiting body grown on the solid state using corn cob and activated bleaching earth (CCABE media) and its mycelium grown in the liquid state. The total phenol and polysaccharide concentrations in hot water extract of fruiting body were approximately 3.6- and 4.3-fold higher than those of the mycelium. Using the hot water extract of fruiting body, the maximum DPPH radical scavenging activity at 9 mg/mL, hydroxyl radical scavenging activity at 12mg/mL, reducing power at 12 mg/mL, and chelating ability at 12 mg/mL were obtained, 80.5%, 72.4%, 0.99 OD (700 nm), and 77.0%, respectively. However, in the case of hydrogen peroxide scavenging activity, the ethanol extract was the highest, 78.7% at 12 mg/mL. The maximum nitrite scavenging activity was obtained, 89.7% at 6 mg/mL of hot water extract from fruiting body. Hot water extracts were more effective than ethanol extracts in scavenging activity on DPPH radicals and hydroxyl radical scavenging, reducing power, and chelating activity of ferrous, whereas ethanol extracts were more effective in hydrogen peroxide scavenging activity as evidenced by their lower EC50 values. These results indicate that the hot water extract of P. ferulae fruiting body using CCABE media has good potential to be used as a source of materials or additives for oxidation suppressant in food, cosmetics and drug compositions.
    Preview · Article · Oct 2012 · Korean Journal of Chemical Engineering
  • Dong-Young Choi · Myung Koo Lee · Jin Tae Hong
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    ABSTRACT: Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining normal neuronal activities. No study has described function of CCR5 in the dopaminergic neurodegeneration in Parkinson's disease. In order to examine effects of CCR5 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration, we employed CCR5 wild type (WT) and knockout (KO) mice. Immunostainings for tyrosine hydroxylase (TH) exhibited that CCR5 KO mice had lower number of TH-positive neurons even in the absence of MPTP. Difference in MPTP (15mg/kg×4 times, 2hr interval)-mediated loss of TH-positive neurons was subtle between CCR5 WT and KO mice, but there was larger dopamine depletion, behavioral impairments and microglial activation in CCR5 deficient mice. Intriguingly, CCR5 KO brains contained higher immunoreactivity for monoamine oxidase (MAO) B which was mainly localized within astrocytes. In agreement with upregulation of MAO B, concentration of MPP+ was higher in the substantia nigra and striatum of CCR5 KO mice after MPTP injection. We found remarkable activation of p38 MAPK in CCR5 deficient mice, which positively regulates MAO B expression. These results indicate that CCR5 deficiency modifies the nigrostriatal dopaminergic neuronal system and bidirectional interaction between neurons and glial cells via CCR5 might be important for dopaminergic neuronal survival.
    No preview · Article · Aug 2012 · Neurobiology of Disease

Publication Stats

1k Citations
243.48 Total Impact Points

Institutions

  • 1993-2015
    • Chungbuk National University
      • • College of Pharmacy
      • • Department of Pharmacy
      Chinsen, Chungcheongbuk-do, South Korea
  • 2003
    • Korea Food and Drug Administration
      Seishō-gun, North Gyeongsang, South Korea
    • Ewha Womans University
      Sŏul, Seoul, South Korea