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  1. AU="Jeongjun Kim"
  2. AU="Marks, Evan A. N."
  3. AU="Thomson, Tina"
  4. AU="Lazaros Iliadis"
  5. AU="Guglielmo, Letterio"
  6. AU="Wilson, Brandon"
  7. AU=Hammerman Marc R.
  8. AU=Bromfield Mahiri
  9. AU=Hunt John T
  10. AU="Nock, Annike Morgane"
  11. AU="Benitah, Salvador Aznar"
  12. AU="Axelgaard, Esben"
  13. AU="Kachingwe, Martin"
  14. AU="Yokoyama, Ryuto"
  15. AU="Luck, Jennifer N"
  16. AU="Min Soo Kim"
  17. AU="Piotr Dylewicz"
  18. AU="Mankel, A"
  19. AU="Lia, Andrea"
  20. AU=Wang Yong
  21. AU="Mckay, Victoria"
  22. AU="Yanqun Liu"
  23. AU="Doyon, Yannick"
  24. AU=Ho-Yen Colan M
  25. AU="Tarnawski, Miroslaw"
  26. AU="Mark Pickering"
  27. AU=Felson Marcus
  28. AU="Antje Garten"
  29. AU="Pijpers, Judith"
  30. AU=Ciacchini Benedetta AU=Ciacchini Benedetta

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  1. Artikel: The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long‐Evans Tokushima fatty rats and HepG2 cells

    Yoon, Seolah / Haerim Lee / Heejeong Yang / Hyunghee Lee / Jeongjun Kim / Jonghoon Lim / Michung Yoon / Soon Shik Shin

    Journal of ethnopharmacology. 2017 Jan. 04, v. 195

    2017  

    Abstract: Hepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica ( ... ...

    Abstract Hepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata, regulates hepatic steatosis and inflammation.The effects of GGH(4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty (OLETF) rats and HepG2 cells were examined using Oil red O, hematoxylin and eosin, and toluidine blue staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay.Administration of GGH(4) to OLETF rats improved hepatic steatosis and lowered serum levels of alanine transaminase, total cholesterol, triglycerides, and free fatty acids. GGH(4) increased mRNA levels of fatty acid oxidation enzymes (ACOX, HD, CPT-1, and MCAD) and decreased mRNA levels of lipogenesis genes (FAS, ACC1, C/EBPα, and SREBP-1c) in the liver of OLETF rats. In addition, infiltration of inflammatory cells and expression of inflammatory cytokines (CD68, TNFα, and MCP-1) in liver tissue were reduced by GGH(4). Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, but GGH(4) inhibited lipid accumulation by regulating the expression of hepatic fatty acid oxidation and lipogenic genes. GGH(4) also increased PPARα reporter gene expression. These effects of GGH(4) were similar to those of the PPARα activator fenofibrate, whereas the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on lipid accumulation in HepG2 cells.These results suggest that GGH(4) inhibits obesity-induced hepatic steatosis and that this process may be mediated by regulation of the expression of PPARα target genes and lipogenic genes. GGH(4) also suppressed obesity-related hepatic inflammation. Thus, GGH(4) may be a promising drug for the treatment of obesity-related liver diseases.
    Schlagwörter alanine transaminase ; Alnus japonica ; antagonists ; beta oxidation ; blood serum ; cholesterol ; Curcuma longa ; drug therapy ; fatty liver ; fenofibrate ; free fatty acids ; gene expression ; human cell lines ; immunohistochemistry ; inflammation ; lipogenesis ; liver ; messenger RNA ; obesity ; oleic acid ; palmitoleic acid ; peroxisome proliferator-activated receptors ; quantitative polymerase chain reaction ; rats ; reporter genes ; staining ; toluidine blue ; traditional medicine ; transcriptional activation ; triacylglycerols ; tumor necrosis factor-alpha
    Sprache Englisch
    Erscheinungsverlauf 2017-0104
    Umfang p. 204-213.
    Erscheinungsort Elsevier Ireland Ltd
    Dokumenttyp Artikel
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2016.11.020
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  2. Artikel: Effect of Gangjihwan on hepatic steatosis and inflammation in high fat diet-fed mice

    Roh, Jong Seong / Haerim Lee / Heejung Yang / Jeongjun Kim / Jonghoon Lim / Michung Yoon / Soon Shik Shin / Yooshik Yoon

    Journal of ethnopharmacology. 2017 July 12, v. 206

    2017  

    Abstract: Gangjihwan (DF), a polyherbal drug composed of Ephedra intermedia Schrenk et C. A. Mayer (Ephedraceae), Lithospermum erythrorhizon Siebold et Zuccarini (Borraginaceae), and Rheum palmatum L. (Polygonaceae), is used to treat obesity in local Korean ... ...

    Abstract Gangjihwan (DF), a polyherbal drug composed of Ephedra intermedia Schrenk et C. A. Mayer (Ephedraceae), Lithospermum erythrorhizon Siebold et Zuccarini (Borraginaceae), and Rheum palmatum L. (Polygonaceae), is used to treat obesity in local Korean clinics. The constituents of DF have traditionally been reported to exert anti-obesity and anti-nonalcoholic fatty liver disease (NAFLD) effects. Thus, we investigated the effects of DF on obesity and NAFLD and the underlying mechanisms.DF was extracted with water (DF-FW), 30% ethyl alcohol (DF-GA30), or 70% ethyl alcohol (DF-GA70). The chemical profile of DF was monitored using high performance liquid chromatography (HPLC)-ultraviolet analysis. The effects of DF on indices of obesity and NAFLD in high fat diet (HFD)-fed C57BL/6J mice and HepG2 cells were examined using quantitative real-time polymerase chain reaction, Oil red O staining, hematoxylin-eosin staining, toluidine blue staining, and immunohistochemistry.The presence of ephedrine, pseudoephedrine, aloe-emodin, and emodin in DF was determined by 3D chromatography using HPLC. Administration of DF-GA70 to HFD-fed obese mice decreased body weight, epididymal adipose tissue mass, and epididymal adipocyte size. DF-GA70 reduced serum levels of free fatty acids and triglycerides. All three DF extracts lowered serum alanine transaminase levels, hepatic lipid accumulation, and infiltration of macrophages, with the largest effects observed for DF-GA70. DF-GA70 increased mRNA levels of fatty acid oxidation genes and decreased mRNA levels of genes for lipogenesis and inflammation in the liver of obese mice. Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, whereas all three DF extracts inhibited lipid accumulation. DF-GA70 also altered the expression of lipolytic and lipogenic genes in HepG2 cells.These results indicate that DF inhibits obesity and obesity-induced severe hepatic steatosis and inflammation without any adverse effects and that these effects may be mediated by regulation of the hepatic expression of lipid metabolism and inflammatory genes. These findings suggest that DF is a safe and efficient anti-obesity and anti-nonalcoholic steatohepatosis drug.
    Schlagwörter adipocytes ; adipose tissue ; adverse effects ; alanine transaminase ; animal disease models ; beta oxidation ; blood serum ; emodin ; Ephedra ; ephedrine ; epididymis ; ethanol ; fatty liver ; free fatty acids ; genes ; high fat diet ; high performance liquid chromatography ; human cell lines ; inflammation ; lipogenesis ; Lithospermum erythrorhizon ; liver ; macrophages ; messenger RNA ; mice ; obesity ; oleic acid ; palmitoleic acid ; pseudoephedrine ; quantitative polymerase chain reaction ; Rheum palmatum ; staining ; toluidine blue ; traditional medicine ; triacylglycerols
    Sprache Englisch
    Erscheinungsverlauf 2017-0712
    Umfang p. 315-326.
    Erscheinungsort Elsevier B.V.
    Dokumenttyp Artikel
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2017.06.008
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  3. Artikel: The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice

    Lim, Jonghoon / Birang Jeong / Haerim Lee / Heejung Yang / Jeongjun Kim / Jiwon Ahn / Joonseong Jang / Michung Yoon / Soon Shik Shin / Yonghyun Park

    Journal of ethnopharmacology. 2018 Oct. 28, v. 225

    2018  

    Abstract: The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents ... ...

    Abstract The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia.This study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved.C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice.Mice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid β-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD.These results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.
    Schlagwörter adipocytes ; adipose tissue ; alanine transaminase ; animal disease models ; anti-obesity agents ; beta oxidation ; blood serum ; collagen ; Ephedra sinica ; epididymis ; fatty acids ; fatty liver ; food consumption ; free fatty acids ; gene expression ; genes ; high fat diet ; immunohistochemistry ; insulin resistance ; low fat diet ; mast cells ; metabolic diseases ; mice ; muscles ; obesity ; quantitative polymerase chain reaction ; Rheum palmatum ; Saccharina japonica ; traditional medicine ; triacylglycerols
    Sprache Englisch
    Erscheinungsverlauf 2018-1028
    Umfang p. 31-41.
    Erscheinungsort Elsevier B.V.
    Dokumenttyp Artikel
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2018.06.034
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  4. Artikel: The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6J mice

    Woo, Sangee / Jeongjun Kim / Michung Yoon / Min-Young Kim / Miso Yoon / Soon Shik Shin / Yeonhee Hong

    Journal of ethnopharmacology. 2016 Feb. 03, v. 178

    2016  

    Abstract: Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. ... ...

    Abstract Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from M. officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy.ALS-L1023 was prepared by a two-step organic solvent fractionation from M. officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches.ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice.These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.
    Schlagwörter adipocytes ; adipogenesis ; adipose tissue ; angiogenesis ; animal disease models ; dose response ; enzyme activity ; fractionation ; gene expression ; high fat diet ; hypertrophy ; in vivo studies ; lipids ; Melissa officinalis ; messenger RNA ; mice ; obesity ; reporter genes ; solvents ; therapeutics ; traditional medicine ; vascular endothelial growth factor A
    Sprache Englisch
    Erscheinungsverlauf 2016-0203
    Umfang p. 238-250.
    Erscheinungsort Elsevier Ireland Ltd
    Dokumenttyp Artikel
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2015.12.015
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  5. Artikel: Herbal composition Gambigyeongsinhwan (4) from Curcuma longa, Alnus japonica, and Massa Medicata Fermentata inhibits lipid accumulation in 3T3-L1 cells and regulates obesity in Otsuka Long-Evans Tokushima Fatty rats

    Sung Roh, Jong / Hyunghee Lee / Jeongjun Kim / Michung Yoon / Miso Yoon / Sangee Woo / Soon Shik Shin / Sun Dong Park

    Journal of ethnopharmacology. 2015 Aug. 02, v. 171

    2015  

    Abstract: Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal composition Gambigyeongsinhwan ( ... ...

    Abstract Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal composition Gambigyeongsinhwan (4) (GGH(4)) composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata.The effects of GGH(4) and the individual components on lipid accumulation in 3T3-L1 adipocytes and body weight gain in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined using Oil red O staining, hematoxylin and eosin staining, quantitative real-time PCR, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay.GGH(4), individual components, and an active principle of Curcuma longa curcumin inhibited lipid accumulation and mRNA levels of adipocyte-specific genes (PPARγ, aP2, and C/EBPα) in 3T3-L1 adipocytes compared with control cells. Treatment with GGH(4), the individual components or curcmumin increased mRNA levels of mitochondrial (CPT-1, MCAD, and VLCAD) and peroxisomal (ACOX and thiolase) PPARα target genes. GGH(4) and the individual components also increased PPARα reporter gene expression compared with control cells. These effects were most prominent in GGH(4)-treated cells. However, the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on adipogenesis. An in vivo study showed that GGH(4) decreased body weight gain, adipose tissue mass, and visceral adipocyte size with increasing mRNA levels of adipose tissue PPARα target genes in OLETF rats.These results demonstrate that GGH(4) has an antiobesity effects through the inhibition of adipocyte lipid accumulation, and this process may be mediated in part through adipose PPARα activation.
    Schlagwörter adipocytes ; adipogenesis ; adipose tissue ; Alnus japonica ; antagonists ; beta oxidation ; body weight changes ; Curcuma longa ; curcumin ; eosin ; gene expression ; hypertrophy ; in vivo studies ; lipids ; messenger RNA ; mitochondria ; obesity ; peroxisome proliferator-activated receptors ; quantitative polymerase chain reaction ; rats ; reporter genes ; staining ; traditional medicine ; transcriptional activation
    Sprache Englisch
    Erscheinungsverlauf 2015-0802
    Umfang p. 287-294.
    Erscheinungsort Elsevier Ireland Ltd
    Dokumenttyp Artikel
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2015.05.056
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  6. Artikel ; Online: Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

    Byung Young Park / Hyunghee Lee / Sangee Woo / Miso Yoon / Jeongjun Kim / Yeonhee Hong / Hee Suk Lee / Eun Kyu Park / Jong Cheon Hahm / Jin Woo Kim / Soon Shik Shin / Min-Young Kim / Michung Yoon

    PLoS ONE, Vol 10, Iss 11, p e

    2015  Band 0141612

    Abstract: It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, ... ...

    Abstract It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 630
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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