The memory-enhancing effects of 7,8,4’-trihydroxyisoflavone, a major metabolite of daidzein, are associated with activation of the cholinergic system and BDNF signaling pathway in mice

Ko, Yong-Hyun,Kwon, Seung-Hwan,Ma, Shi-Xun,Seo, Jee-Yeon,Lee, Bo-Ram,Kim, Kyungin,Kim, Sun Yeou,Lee, Seok-Yong,Jang, Choon-Gon Elsevier 2018 Brain research bulletin Vol.142 No.-

<P><B>Abstract</B></P> <P>Daidzein is one of the dietary isoflavones present in soybean-based products. After ingestion, daidzein is bioconverted into its major metabolite, 7,8,4’-trihydroxyisoflavone (THIF). Given the pharmacological importance of daidzein, 7,8,4’-THIF has also attracted the interest of researchers. However, there are no reports on the effects of 7,8,4’-THIF on cognition and memory with regard to the cholinergic system. Therefore, this study sought to evaluate the memory-enhancing effects of 7,8,4’-THIF in mice. Treatment with 7,8,4’-THIF ameliorated the cognitive impairments induced by scopolamine, a muscarinic acetylcholine receptor antagonist, in the Y-maze and passive avoidance tests. Interestingly, 7,8,4’-THIF treatment also improved cognitive function in normal mice. This treatment was also able to reverse acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus. Finally, 7,8,4’-THIF significantly increased the expression levels of the following molecules in the hippocampus: brain-derived neurotrophic factor (BDNF); phospho extracellular signal-regulated kinase (ERK); phospho cAMP response element binding (CREB); and choline acetyltransferase (ChAT). Our data suggest that 7,8,4’-THIF, a metabolized product of daidzein, improves cognitive function by activating the cholinergic system and the BDNF/ERK/CREB signaling pathway in mice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 7,8,4’-Trihydroxyisoflavone (THIF) improved cognitive and memory function in mice. </LI> <LI> 7,8,4’-THIF restored the hippocampal cholinergic dysfunction and oxidative damage. </LI> <LI> 7,8,4’-THIF enhanced BDNF signaling pathway in the hippocampus of mice. </LI> </UL> </P>

Is Myocardial Infarction in Patients without Significant Stenosis on a Coronary Angiogram as Benign as Believed?

Rhew, Shi Hyun,Ahn, Youngkeun,Kim, Min Chul,Jang, Su Young,Cho, Kyung Hoon,Hwang, Seung Hwan,Lee, Min Goo,Ko, Jum Suk,Park, Keun Ho,Sim, Doo Sun,Yoon, Nam Sik,Yoon, Hyun Ju,Kim, Kye Hun,Hong, Young Jo Chonnam National University Medical School 2012 CMJ Vol.48 No.1

<P>The present study aimed to investigate the clinical characteristics and 1-year outcomes of acute myocardial infarction (AMI) patients without significant stenosis on a coronary angiogram comparison with the clinical characteristics and outcomes of patients with significant coronary artery stenosis. A total of 1,220 patients with AMI were retrospectively classified into Group I (≥50% diameter stenosis, n=1,120) and Group II (<50%, n=100). Group II was further divided into two subgroups according to the underlying etiology: cryptogenic (Group II-a, n=54) and those with possible causative factors (Group II-b, n=46). Patients in Group II were younger, were more likely to be women, and were less likely to smoke and to have diabetes mellitus than were patients in Group I. The levels of cardiac enzymes, LDL-cholesterol levels, and the apo-B/A1 ratio were lower in Group II. However, 1-month and 12-month rates of major adverse cardiac events (MACE) were not significantly different between the two groups. The Group II-b subgroup comprised 29 patients with vasospasm, 11 with myocardial bridge, and 6 with spontaneous thrombolysis. Left ventricular ejection fraction and creatinine clearance were lower and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were higher in Group II-a than in Group II-b. However, outcomes including MACE and mortality at 12 months were not significantly different between the two subgroups. The 1-year outcomes of patients in Group II were similar to those of patients in Group I. The clinical outcomes in Group II-a were also similar to those of Group II-b, although the former group showed higher levels of NT-proBNP and hs-CRP.</P>

The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells

( Seung Hwan Kwon ),( Shi Xun Ma ),( Ji Young Hwang ),( Yong Hyun Ko ),( Ji Yeon Seo ),( Bo Ram Lee ),( Seok Yong Lee ),( Choon Gon Jang ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase kinase-3β (GSK-3β), and their downstream transcription factor, nuclear factor-kappa B (NF-κB). EUE also blocked the nuclear translocation of NF-κB and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and PGE2 production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and GSK-3β, consequently suppressing NF-κB activation and inducing Nrf2-dependent HO-1 activation.

Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells

( Seung-hwan Kwon ),( Shi-xun Ma ),( Yong-hyun Ko ),( Jee-yeon Seo ),( Bo-ram Lee ),( Taek Hwan Lee ),( Sun Yeou Kim ),( Seok-yong Lee ),( Choon-gon Jang ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-κB p65). VBME significantly inhibited LPS-induced production of NO and PGE₂ and LPS-mediated upregulation of iNOS and COX-2 expression in a dosedependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-κB p65 translocation by blocking IκB- α, phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-κB signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells

Kwon, Seung-Hwan,Ma, Shi-Xun,Hwang, Ji-Young,Ko, Yong-Hyun,Seo, Ji-Yeon,Lee, Bo-Ram,Lee, Seok-Yong,Jang, Choon-Gon The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells

Kwon, Seung-Hwan,Ma, Shi-Xun,Ko, Yong-Hyun,Seo, Jee-Yeon,Lee, Bo-Ram,Lee, Taek Hwan,Kim, Sun Yeou,Lee, Seok-Yong,Jang, Choon-Gon The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-${\kappa}B$ p65). VBME significantly inhibited LPS-induced production of NO and $PGE_2$ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-${\kappa}B$ p65 translocation by blocking $I{\kappa}B-{\alpha}$ phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-${\kappa}B$ signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

Electroreflectance Study of CIGS Thin Film Solar Cells

Hyun-Jun Jo,Dong-Hwan Jeon,Byoung Soo Ko,Shi-Joon Sung,In-Ho Bae,Dae-Hwan Kim 한국진공학회 2013 한국진공학회 학술발표회초록집 Vol.2013 No.2

Single-step sulfo-selenization method for achieving low open circuit voltage deficit with band gap front-graded Cu₂ZnSn(S,Se)₄ thin films

Hwang, Dae-Kue,Ko, Byoung-Soo,Jeon, Dong-Hwan,Kang, Jin-Kyu,Sung, Shi-Joon,Yang, Kee-Jeong,Nam, Dahyun,Cho, Soyeon,Cheong, Hyeonsik,Kim, Dae-Hwan Elsevier 2017 Solar energy materials and solar cells Vol.161 No.-

<P><B>Abstract</B></P> <P>In this study, we investigate the electrical, structural, and optical properties of band gap front-graded Cu<SUB>2</SUB>ZnSn(S,Se)<SUB>4</SUB> (CZTSSe) thin films grown by a modified single-step sulfo-selenization process from copper-poor and zinc-rich precursor metallic stacks prepared by co-evaporation. To investigate how the bandgap was graded in connection with the compositional distribution, we calculated the bandgap energy distribution along the film thickness, based on the transmission electron microscopy and energy-dispersive X-ray spectroscopy composition profile. The band gap of the CZTSSe phase with high S content near the surface layer is determined to be 1.161eV. From the surface to the bottom, there is a decrease in the S content of the CZTSSe phase, and the band gap subsequently decreases to, 1.029eV, close to the value of CZTSe. From the results of dimpling-Raman and scanning transmission electron microscopy line scanning, we confirm that the S content drastically increases from the bottom to the top surface of the CZTSSe thin film. The CZTSSe thin-film solar cell exhibits a power conversion efficiency (PCE) of 10.33%, with an open-circuit voltage (<I>V</I> <SUB> <I>oc</I> </SUB>) of 0.505 V, short-circuit current density (<I>J</I> <SUB> <I>sc</I> </SUB>) of 31.61mA/cm<SUP>2</SUP>, fill factor (FF) of 64.6%, and <I>V</I> <SUB> <I>oc</I> </SUB> deficit of 525mV. Compared with the performance of the CZTSe solar cell, which had PCE of 7.23%, <I>V</I> <SUB> <I>oc</I> </SUB> of 0.424 V, <I>J</I> <SUB> <I>sc</I> </SUB> of 32.83mAcm<SUP>−2</SUP>, FF of 51.9%, and <I>V</I> <SUB> <I>oc</I> </SUB> deficit of 576mV, the <I>V</I> <SUB> <I>oc</I> </SUB> and <I>V</I> <SUB> <I>oc</I> </SUB> deficit of the CZTSSe cell improved considerably. The high <I>V</I> <SUB> <I>oc</I> </SUB>, low <I>V</I> <SUB> <I>oc</I> </SUB> deficit, and less loss of <I>J</I> <SUB> <I>sc</I> </SUB> are attributed to the effect of band gap front-grading induced by S grading into the CZTSSe thin film.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We investigate the properties of band gap front-graded CZTSSe thin films. </LI> <LI> The precursors are annealed by a modified single-step sulfo-selenization process. </LI> <LI> The CZTSSe thin-film solar cell exhibits power conversion efficiency of 10.33%. </LI> <LI> The high <I>V</I> <SUB> <I>oc</I> </SUB> and less loss of <I>J</I> <SUB> <I>sc</I> </SUB> are attributed to the band gap front-grading. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice

( Sa Ik Hong ),( Seung Hwan Kwon ),( Ji Young Hwang ),( Shi Xun Ma ),( Jee Yeon Seo ),( Yong Hyun Ko ),( Hyoung Chun Kim ),( Seok Yong Lee ),( Choon Gon Jang ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.2

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

A New Tricyclic Undecose Nucleoside from Streptomyces scopuliridis RB72

Choi, Chun Whan,Choi, Jung-Sup,Ko, Young Kwan,Kim, Chang-Jin,Kim, Young Ho,Oh, Joa Sub,Ryu, Shi Yong,Yon, Gyu Hwan Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.4