Ameliorative Effect of <i>Ecklonia cava</i> Polyphenol Extract on Renal Inflammation Associated with Aberrant Energy Metabolism and Oxidative Stress in High Fat Diet-Induced Obese Mice

Eo, Hyeyoon,Park, Ji Eun,Jeon, You-jin,Lim, Yunsook American Chemical Society 2017 Journal of agricultural and food chemistry Vol.65 No.19

<P>Immoderate fat accumulation causes both oxidative stress and inflammation, which can induce kidney damage in obesity. Previously, Ecklonia cava has shown anti-inflammatory and antioxidative effects. Our group aimed to investigate whether E. cava polyphenol extract (ECPE) improves renal damage in high fat diet (HFD)-induced obese mice through regulation of not only energy metabolism but also oxidative stress and inflammation. After obesity induction by HFD, the mice were treated with different dosages of ECPE (100 or 500 mg/kg/day) by gavage for 12 weeks. ECPE treatment lowered the protein levels related to lipid accumulation (SREBP1c, ACC & FAS), inflammation (NLRP3 inflammasome, Na kappa B, MCP-1, TNF-alpha & CRP), and oxidative stress (Nrf2, HO-1, MnSOD, NQO1, GPx, 4-HNE and protein carbonyls) in HFD induced obese mice. Moreover, ECPE supplementation significantly up-regulated renal SIRT1, PGC-l alpha, and AMPK, which are associated with renal energy metabolism. Consequently, the results provide novel insights into the anti-inflammatory roles of ECPE in obesity-induced renal inflammation.</P>

Brown Alga <i>Ecklonia cava</i> Polyphenol Extract Ameliorates Hepatic Lipogenesis, Oxidative Stress, and Inflammation by Activation of AMPK and SIRT1 in High-Fat Diet-Induced Obese Mice

Eo, Hyeyoon,Jeon, You-jin,Lee, Myoungsook,Lim, Yunsook American Chemical Society 2015 Journal of agricultural and food chemistry Vol.63 No.1

<P>Obesity is considered to be a metaflammatory condition. <I>Ecklonia cava</I>, brown algae rich in polyphenols, has shown strong antioxidant activity in vitro. This study investigated the effect of <I>E. cava</I> polyphenol extract (ECPE) on the regulation of fat metabolism, inflammation, and the antioxidant defense system in high fat diet-induced obese mice. After obesity was induced by a high-fat diet (HFD), the mice were administered ECPE by gavage for 5 days/12 weeks. ECPE supplementation reduced body weight gain, adipose tissue mass, plasma lipid profiles, hepatic fat deposition, insulin resistance, and the plasma leptin/adiponectin ratio derived from HFD-induced obesity. Moreover, ECPE supplementation selectively ameliorated hepatic protein levels associated with lipogenesis, inflammation, and the antioxidant defense system as well as activation of AMPK and SIRT1. Collectively, ECPE supplement might have potential antiobesity effects via regulation of AMPK and SIRT1 in HFD-induced obesity.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2015/jafcau.2015.63.issue-1/jf502830b/production/images/medium/jf-2014-02830b_0008.gif'></P>

Ukgansan protects dopaminergic neurons from 6-hydroxydopamine neurotoxicity via activation of the nuclear factor (erythroid-derived 2)-like 2 factor signaling pathway

Eo, Hyeyoon,Huh, Eugene,Sim, Yeomoon,Oh, Myung Sook Elsevier 2019 Neurochemistry International Vol.122 No.-

<P><B>Abstract</B></P> <P>The sustenance of redox homeostasis in brain is the crucial factor to treat Parkinson's disease (PD). Nuclear factor (erythroid-derived 2)-like 2 factor (Nrf2)-mediated antioxidant response is well known for the main cellular endogenous defense mechanisms against oxidative stress. This study investigated for the first time the effects and possible mechanisms of action of Ukgansan on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in both <I>in vitro</I> and <I>in vivo</I> models of PD. We investigated the protective effect of Ukgansan against 6-OHDA with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. In addition, we demonstrated that Ukgansan significantly increased the expression of antioxidant response elements (ARE) and pro-survival protein as Bcl2 and suppressed the expression of pro-apoptotic factors, such as Bax, cytochrome <I>c</I>, and caspase-3 using immunoblotting. For the <I>in vivo</I> study, we used a mouse model of PD involving stereotaxic injection of 6-OHDA into the striatum (ST). Ukgansan alleviated motor dysfunctions induced by 6-OHDA followed by pole, open-field, and rotation tests. Dopaminergic neuronal loss and Nrf2 activation were evaluated by immunohistochemistry in the mouse ST and substantia nigra pars compacta (SNpc) regions. Ukgansan significantly protected dopaminergic neurons from 6-OHDA toxicity in mouse ST and SNpc by activating Nrf2. These results indicate that Ukgansan inhibited 6-OHDA-induced dopaminergic neuronal cell damage via activation of Nrf2 and its related factors in 6-OHDA-induced dopaminergic loss <I>in vitro</I> and <I>in vivo</I>. Thus, Ukgansan might delay the progression of PD via maintenance of redox homeostasis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> UGS promotes the antioxidant defense system via activating Nrf2 against 6-OHDA. </LI> <LI> Nrf2 activation induces the cell survival signaling pathway in dopaminergic neurons. </LI> <LI> UGS protects the dopaminergic neuron against 6-OHDA in <I>in vitro</I> and <I>in vivo</I> systems. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation

Hanna Shin,Hyeyoon Eo,Yunsook Lim 한국영양학회 2016 Nutrition Research and Practice Vol.10 No.1

BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on NFκB associated inflammatory response (phosphorylated inhibitory kappa B-α, interleukin-1β, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor β-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: the results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

Protective effects of a herbal extract combination of <i>Bupleurum falcatum</i>, <i>Paeonia suffruticosa</i>, and <i>Angelica dahurica</i> against MPTP-induced neurotoxicity via regulation of nuclear receptor-related 1 protein

Sim, Yeomoon,Park, Gunhyuk,Eo, Hyeyoon,Huh, Eugene,Gu, Pil Sung,Hong, Seon-Pyo,Pak, Youngmi Kim,Oh, Myung Sook Elsevier 2017 NEUROSCIENCE Vol.340 No.-

<P><B>Abstract</B></P> <P>Parkinson’s disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum. Recent studies have demonstrated that the nuclear receptor-related 1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2). The aim of this study was to investigate the protective effects of a herbal extract combination, consisting of <I>Bupleurum falcatum</I>, <I>Paeonia suffruticosa</I>, and <I>Angelica dahurica</I> (MABH), on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate possible mechanisms of action focusing on Nurr1. In a subacute mouse model of MPTP-induced PD, MABH treatment resulted in recovery from movement impairments. MABH prevented dopamine depletion and protected against dopaminergic neuronal degradation induced by MPTP. Additionally, MABH increased Nurr1 expression in the SNpc of mice. To evaluate the effects of MABH on Nurr1 expression, we measured the protein levels of Nurr1 and its regulating factors using Western blot analysis in PC12 cells. MABH treatment induced the phosphorylation of extracellular signal-regulated kinase protein via increasing the protein expression levels of Nurr1 and ultimately the levels of TH, VMAT2, and DAT. These results indicate that MABH has protective effects on dopaminergic neurons in a mouse model of PD by regulating Nurr1.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MABH improved MPTP-induced movement impairments in mice. </LI> <LI> MABH prevented dopamine depletion and protected against MPTP-induced dopaminergic neuron damage in mice. </LI> <LI> MABH increased Nurr1 expression in the SNpc of mice. </LI> <LI> MABH increased TH, DAT, and VMAT2 expressions by upregulating Nurr1 via phosphorylation of ERK in PC12 cells. </LI> </UL> </P>

Effect of combined mulberry leaf and fruit extract on liver and skin cholesterol transporters in high fat diet-induced obese mice

Giuseppe Valacchi,Giuseppe Belmonte,Clelia Miracco,Hyeyoon Eo,Yunsook Lim 한국영양학회 2014 Nutrition Research and Practice Vol.8 No.1

Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications.