3-<i>O</i>-Glucosylation of quercetin enhances inhibitory effects on the adipocyte differentiation and lipogenesis

Lee, Chang Won,Seo, Jeong Yeon,Lee, Jisun,Choi, Ji Won,Cho, Sarang,Bae, Jae Youn,Sohng, Jae Kyung,Kim, Sung Oog,Kim, Jihoon,Park, Yong Il EDITIONS SCIENTIFIQUES ELSEVIER 2017 BIOMEDICINE AND PHARMACOTHERAPY Vol.95 No.-

<P><B>Abstract</B></P> <P>Glycosylation of natural flavonoids with various sugar moieties can affect their physicochemical and pharmacological properties. In this study, the plant flavonoids quercetin aglycon (Quer) and quercetin 3-<I>O</I>-glucoside (Q3G) were evaluated and compared for their potential anti-obesity effects. The Q3G dose-dependently reduced the TG contents and lipid accumulation in 3T3-L1 adipocyte cells, by 52% and 60% at 20μM, respectively, compared to differentiated control (100%), which were 1.6-fold and 2.4-fold higher reduction than Quer. The Q3G (20μM) also more significantly reduced the expression of adipogenic markers such as C/EBP-β, C/EBP-α, PPAR-γ, and aP2 than Quer, indicating that the Q3G suppresses both adipocyte differentiation and lipogenesis more effectively than Quer <I>in vitro</I>. Comparing to those in the high-fat diet (HFD) fed mice control group for 10 weeks, both the body and liver weights and the size of adipocytes in epididymal adipose tissues were significantly reduced in HFD mice fed with Q3G for another 6 weeks (30mg/kg body weight by oral administration), accompanied by the reductions of TG, total cholesterol, and HDL-cholesterol in serum. The Q3G also reduced the levels of the lipid metabolism-associated proteins, PPAR-γ, SREBP-1c, and FAS in the liver tissues. These results clearly demonstrated that Q3G exhibits a stronger anti-obesity effect than Quer and its anti-obesity effect is mediated via inhibition of adipocyte differentiation and lipogenesis, decreasing serum lipid levels by altering hepatic lipid metabolism, and reducing body weight gain. The results of this study suggest that the Q3G, but not Quer, can be a potent functional ingredient of beneficial health foods or a therapeutic agent to prevent or treat obesity.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

P03-183 Association analysis of heat shock protein 70 gene polymorphisms in schizophrenia

Editions scientifiques Elsevier ; Elsevier Science 2009 European psychiatry Vol.24 No.suppl1

TAAR6 variation effect on clinic presentation and outcome in a sample of schizophrenic in-patients: An open label study

Pae, C.U.,Drago, A.,Kim, J.J.,Patkar, A.A.,Jun, T.Y.,Lee, C.,Mandelli, L.,De Ronchi, D.,Paik, I.H.,Serretti, A. Editions scientifiques Elsevier ; Elsevier Science 2008 European psychiatry Vol.23 No.6

We recently reported an association between TAAR6 (trace amine associated receptor 6 gene) variations and schizophrenia (SZ). We now report an association of a set of TAAR6 variations and clinical presentation and outcome in a sample of 240 SZ Korean patients. Patients were selected by a Structured Clinical Interview, DSM-IV Axis I disorders - Clinical Version (SCID-CV). Other psychiatric or neurologic disorders, as well as medical diseases, were exclusion criteria. To assess symptom severity, patients were administered the CGI scale and the PANSS at baseline and at the moment of discharge, 1 month later on average. TAAR6 variations rs6903874, rs7452939, rs8192625 and rs4305745 were investigated; rs6903874, rs7452939 and rs8192625 entered the statistical investigation after LD analysis. Rs8192625 G/G homozygosis was found to be significantly associated both with a worse clinical presentation at PANSS total and positive scores and with a shorter period of illness before hospitalization. No haplotype significant findings were found. The present study stands for a role of the TAAR6 in the clinical presentation of SZ. Moreover, our results show that this genetic effect may be counteracted by a correct treatment. Haplotype analysis was not informative in our sample, probably also because of the incomplete SNPs' coverage of the gene we performed. Further studies in this direction are warranted.

The protective role of <i>Piper nigrum</i> fruit extract in an ovalbumin-induced allergic rhinitis by targeting of NFκBp65 and STAT3 signalings

Bui, Thi Tho,Piao, Chun Hua,Hyeon, Eunjin,Fan, Yanjing,Van Nguyen, Thi,Jung, Sun Young,Choi, Dae Woon,Lee, So-young,Shin, Hee Soon,Song, Chang Ho,Chai, Ok Hee EDITIONS SCIENTIFIQUES ELSEVIER 2019 BIOMEDICINE AND PHARMACOTHERAPY Vol.109 No.-

<P><B>Abstract</B></P> <P> <I>Piper nigrum</I> L. is commonly used as a traditional medicine and food in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of <I>P. nigrum</I> on allergic rhinitis (AR) has been unclear. In the present study, an OVA-induced AR mice model were established to investigate the anti-allergic, anti-inflammation properties of <I>P. nigrum</I> fruit extract (PNE). Oral administrations of PNE inhibited the allergic nasal symptoms including rubbing and sneezing in the early-phage of AR. In both NALF and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils in NALF. Additionally, PNE prevented the activation of STAT3 and NFκBp65 signaling in the cytoplasm which led to increasing the synthesis of the anti-inflammatory Th1 cytokines and suppressing the inflammatory Th2, Th17 cytokines. These obtained results suggest that PNE has the promising strategy for immunotherapy in allergic rhinitis disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The anti-allergic rhinitis effect of <I>Piper nigrum</I> is investigated. </LI> <LI> <I>Piper nigrum</I> ameliorates nasal symptoms and mucosal swelling. </LI> <LI> <I>Piper nigrum</I> prevents the activation of STAT3 and NFκBp65 signaling. </LI> <LI> <I>Piper nigrum</I> provides a promising strategy for immunotherapy for allergic rhinitis treatment. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Magnesium and calcium-enriched deep-sea water promotes mitochondrial biogenesis by AMPK-activated signals pathway in 3T3-L1 preadipocytes

Ha, Byung Geun,Moon, Deok-Soo,Kim, Hyeon Ju,Shon, Yun Hee EDITIONS SCIENTIFIQUES ELSEVIER 2016 BIOMEDICINE AND PHARMACOTHERAPY Vol.83 No.-

<P><B>Abstract</B></P> <P>Recent studies showed that deficiencies of essential minerals including Mg, Ca, and K, and trace minerals including Se, Zn, and V, have implications for the development, prevention, and treatment of several chronic diseases including obesity and type 2 diabetes. Our previous studies revealed that balanced deep-sea water (BDSW), which is composed of desalinated water enriched with Mg and Ca, has potential as a treatment for diabetes and obesity. In this study, to determine whether BDSW regulates mitochondrial biogenesis and function, we investigated its effects on mitochondrial DNA (mtDNA) content, mitochondrial enzyme activity, expression of key transcription factors and mitochondria-specific genes, phosphorylation of signaling molecules associated with mitochondrial biogenesis, and mitochondrial function in 3T3-L1 preadipocytes. BDSW increased mitochondrial biogenesis in a dose-dependent manner. Quantitative real-time PCR revealed that BDSW enhances expression of PGC1-α, NRF1, and TFAM genes. Upregulation of these genes was supported by increased mitochondria staining, CytC oxidase activity, and AMPK phosphorylation. The stimulatory effect of BDSW on mitochondrial biogenesis and function suggests a novel mechanism for BDSW-induced anti-diabetic and anti-obesity action.</P>

Sulforaphane prevents dexamethasone-induced muscle atrophy via regulation of the Akt/Foxo1 axis in C2C12 myotubes

Son, Young Hoon,Jang, Eun Jeong,Kim, Young Woo,Lee, Ju-Hee EDITIONS SCIENTIFIQUES ELSEVIER 2017 BIOMEDICINE AND PHARMACOTHERAPY Vol.95 No.-

<P><B>Abstract</B></P> <P>Muscle atrophy occurs in various catabolic conditions, including hormone imbalance, severe injury, sepsis, cancer, and aging. Dexamethasone (DEX) is a synthetic glucocorticoid and is used an anti-inflammatory agent. However, when chronically used, it is accompanied by side effects, such as, muscle atrophy, diabetes mellitus, and obesity. In this study, we investigated the effect of sulforaphane (SFN) on DEX-induced muscle atrophy and the underlying mechanisms involved. DEX induced muscle atrophy was accompanied by increased muscle specific ubiquitin E3 ligase markers, such as, Atrogin-1 and myostatin, and decreased MyoD in C2C12 myotubes. To investigate the role played by SFN in DEX-induced muscle atrophy, we quantified mRNA levels of muscle atrophy markers, protein synthesis using a puromycin incorporation assay, protein degradation by ubiquitination, and myotube diameters by PAS staining in C2C12 myotubes co-treated with DEX and SFN. Interestingly, SFN effectively prevented myostatin and Atrogin-1 mRNA upregulations by DEX, increased the mRNA level of MyoD, and consequently, reduced protein degradation. Furthermore, SFN enhanced protein synthesis through a Foxo-dependent pathway by activating Akt, and thus, increased myotube diameters. These results show SFN inhibits DEX-induced muscle atrophy in C2C12 myotubes via Akt/Foxo signaling.</P>

Anti-inflammatory effects of trans-anethole in a mouse model of chronic obstructive pulmonary disease

Kim, K.Y.,Lee, H.S.,Seol, G.H. EDITIONS SCIENTIFIQUES ELSEVIER 2017 BIOMEDICINE AND PHARMACOTHERAPY Vol.91 No.-

<P>Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that is generally characterized by progressive and irreversible airflow obstruction and alveolar destruction. Long-term treatment with current medications has been associated with various adverse effects, indicating a need for alternative approaches for the prevention and treatment of COPD. This study investigated the mechanism underlying the effects of trans-anethole in a mouse model of COPD induced by porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS). BALB/c mice were orally administered trans-anethole (62.5, 125, 250, or 500 mg/kg) 2 h before intranasal challenge with 1.2 units of PPE and 7 mu g of LPS. Lactate dehydrogenase (LDH) activity, cell counts, lung histology, cytokine production, and blood pressure were analyzed. Trans-anethole reduced LDH activity and inflammatory cell counts, including macrophage, neutrophil, and lymphocyte counts. trans-anethole 125 mg/kg restored the histopathological changes induced in mouse lungs by PPE and LPS. trans-anethole reduced the serum concentrations of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as significantly reducing blood pressure during chronic inflammation. Trans-anethole ameliorated chronic lung inflammation in a mouse model of COPD by reducing the serum concentrations of pro-inflammatory cytokines such as TNF-alpha and IL-6, and by reducing blood pressure. The present results indicate that trans-anethole may be a potential therapeutic agent for prophylaxis and treatment in patients with chronic lung inflammation. (C) 2017 Elsevier Masson SAS. All rights reserved.</P>

7,8-Dihydroxyflavone attenuates TNF-α-induced skin aging in Hs68 human dermal fibroblast cells via down-regulation of the MAPKs/Akt signaling pathways

Choi, Ji Won,Lee, Jisun,Park, Yong Il EDITIONS SCIENTIFIQUES ELSEVIER 2017 BIOMEDICINE AND PHARMACOTHERAPY Vol.95 No.-

<P><B>Abstract</B></P> <P>7,8-Dihydroxyflavone (7,8-DHF, 7,8-dihydroxy-2-phenyl-4H-chromen-4-one) is a natural flavone found in plants and has been frequently reported to show anti-inflammatory and anti-oxidant properties. Skin aging is induced mainly by oxidative stress. In the present study, we evaluated 7,8-DHF for its potential anti-aging effects for skin using Hs68 human dermal fibroblast cells. To establish aged skin cell model, Hs68 cells were treated with tumor necrosis factor-α (TNF-α) for 18h 7,8-DHF (0–10μM) induced collagen synthesis and suppressed the expression of matrix metalloproteinase 1 (MMP 1) in a dose-dependent manner. 7,8-DHF also significantly reduced the generation of intracellular reactive oxygen species (ROS), induced the expression of anti-oxidant enzymes, such as catalase, manganese superoxide dismutase (Mn-SOD), and heme oxygenase-1 (HO-1), and scavenged DPPH free radicals. 7,8-DHF also disturbed the mitogen-activated protein kinases (MAPKs) and Akt signaling pathways that participate in the aging process. 7,8-DHF exerted potent anti-aging effects by inhibiting MMP 1 expression and inducing Type I collagen synthesis in Hs68 cells. 7,8-DHF effectively attenuated oxidative stress by up-regulating the anti-oxidant enzymes catalase, Mn-SOD, and HO-1, and reducing activation of the Akt and MAPKs signaling pathways in aged skin cells. These results suggest that 7,8-DHF can be used as a potent facultative ingredient in health-beneficial agents to prevent or treat the skin aging or inflammatory skin disorders.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Subcritical water-hydrolyzed fish collagen ameliorates survival of endotoxemic mice by inhibiting HMGB1 release in a HO-1-dependent manner

Ahn, Min Young,Hwang, Jung Seok,Ham, Sun Ah,Hur, Jinwoo,Jo, Yeonji,Lee, SangYoon,Choi, Mi-Jung,Han, Sung Gu,Seo, Han Geuk EDITIONS SCIENTIFIQUES ELSEVIER 2017 BIOMEDICINE AND PHARMACOTHERAPY Vol.93 No.-

<P><B>Abstract</B></P> <P>To investigate potential mechanisms underlying the bioactivity of hydrolyzed fish collagen, we examined the anti-inflammatory actions of subcritical water-hydrolyzed fish collagen (SWFC) in lipopolysaccharide (LPS)-triggered inflammation and endotoxemia. SWFC markedly inhibited LPS-stimulated release of high mobility group box 1 (HMGB1) in murine RAW264.7 macrophages, along with decreased cytosolic translocation of HMGB1. Both the protein and mRNA levels of heme oxygenase-1 (HO-1) were significantly upregulated in SWFC-treated RAW 264.7 cells in an Nrf2-dependent manner. In line with these effects of SWFC, both HO-1 siRNA and ZnPPIX (zinc protoporphyrin IX) actually attenuated the effects of SWFC on HMGB1 release stimulated by LPS, indicating a possible mechanism by which SWFC modulates HMGB1 release through HO-1 signaling. Notably, administration of SWFC improved the survival rates of LPS-injected endotoxemic mice, in which the serum level of HMGB1 was significantly reduced. Taken together, these results indicate that the anti-inflammatory activities of SWFC are achieved by inhibiting HMGB1 release induced by LPS in a HO-1-sensitive manner.</P>

Novel phyto-derivative BRM270 inhibits hepatocellular carcinoma cells proliferation by inducing G2/M phase cell cycle arrest and apoptosis in xenograft mice model

Kumar Mongre, Raj,Sharma, Neelesh,Singh Sodhi, Simrinder,Ghosh, Mrinmoy,Kumar Singh, Amit,Kim, Nameun,Park, Yang Ho,Shin, Young Gyu,Kim, Sung Jin,Jiao Jiao, Zhang,Huynh, Do Luong,Jeong, Dong Kee EDITIONS SCIENTIFIQUES ELSEVIER 2017 BIOMEDICINE AND PHARMACOTHERAPY Vol.87 No.-

<P><B>Abstract</B></P> <P>Hepatocellular carcinoma (HCC) is a major threat to human health worldwide and development of novel antineoplastic drug is demanding task. BRM270 is a proprietary combination of traditional medicinal herbs, has been shown to be effective against a wide range of stem-like cancer initiating cells (SLCICs). However, the underlying mechanism and antitumor efficacy of BRM270 in human hepatocellular carcinoma (HCC) cells have not been well elucidated till date. Here we studied the tumoricidal effect of BRM270 on human-CD133<SUP>+</SUP> expressing stem-like HepG-2 and SNU-398 cells. Gene expression profiling by qPCR and specific cellular protein expressions was measured using immunocytochemistry/western blot analysis. <I>In vivo</I> efficacy of BRM270 has been elucidated in the SLCICs induced xenograft model. In addition, 2DG-(2-Deoxy-<SMALL>D</SMALL>-Glucose) optical-probe guided tumor monitoring was performed to delineate the size and extent of metastasized tumor. Significant (<I>P</I> <I><</I> 0.05) induction of Annexin-V positive cell population and dose-dependent upregulation of caspase-3 confirmed apoptotic cell death by pre/late apoptosis. In addition, bright field and fluorescence microscopy of treated cells revealed apoptotic morphology and DNA fragmentation in Hoechst33342 staining. Levels of c-Myc, Bcl-2 and c-Jun as invasive potential apoptotic marker were detected using qPCR/Western blot. Moreover, BRM270 significantly (<I>P</I> <I><</I> 0.05) increased survival rate that observed by Kaplan-Meier log rank test. In conclusion, these results indicate that BRM270 can effectively inhibit proliferation and induce apoptosis in hepatoma cells by down-regulating CyclinD1/Bcl2 mediated c-Jun apoptotic pathway.</P>