Anti-obese and Blood Flow Improvement Activities of Ginseng Berry on the 45%Kcal High Fat Diet Supplied Mouse
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Objectives : The present study investigated the anti-obese and blood flow improvement activities of aqueous extracts of ginseng berry (GBe) on the mild diabetic obese mice as compared with metformin. Methods : After end of 56 days of continuous oral administrations of GBe 150, 100 and 50 mg/kg, or metformin 250 mg/kg, anti-obese and blood flow improvement effects - the changes of body weights, body and abdominal fat density by in live dual-energy x-ray absorptionmetry (DEXA), tail bleeding time, prothrombin time (PT), activated partial thromboplastin time (aPTT), serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) levels, aorta and serum cyclic guanosine monophosphate (cGMP), nitric oxide (NO) and endothelin (ET)-1 levels, aorta phosphorylated PI3K (pPI3K), phosphorylated Akt (pAkt) and phosphorylated p38 MAPK (pp38 MAPK) levels were systemically analyzed. In addition, aorta vascular dilation and constriction related gene mRNA expressions - PI3K, Akt, eNOS, p38 MAPK and ET-1 were also analyzed by realtime RT-PCR. Results : The obesity and related blood flow impairment, induced by 84 days of continuous HFD supply, were significantly inhibited by 56 days of continuous oral treatment of GBe 150, 100 and 50 mg/kg, dose-dependently, and they also dramatically normalized the changes of the aorta vascular dilation and constriction related gene mRNA expressions, also dose-dependently. Especially, GBe 150 mg/kg constantly showed favorable inhibitory activities against type II diabetes related obesity and vascular disorders through PI3K/Akt pathway and p38 MAPK mediated cGMP, NO and ET-1 expression modulatory activities, as comparable to those of metformin 250 mg/kg in HFD mice. Conclusion : By assessing the key parameters for anti-obese and blood flow improvement activities on the HFD-induced mild diabetic obese mice, the present work demonstrated that GBe 150, 100 and 50 mg/kg showed favorable anti-obese and blood flow improvement effects in HFD-induced type II diabetic mice, through PI3K/Akt pathway and p38 MAPK mediated cGMP, NO and ET-1 expression modulatory activities.
Abstract
Objectives : The present study investigated the anti-obese and blood flow improvement activities of aqueous extracts of ginseng berry (GBe) on the mild diabetic obese mice as compared with metformin. Methods : After end of 56 days of continuous oral administrations of GBe 150, 100 and 50 mg/kg, or metformin 250 mg/kg, anti-obese and blood flow improvement effects - the changes of body weights, body and abdominal fat density by in live dual-energy x-ray absorptionmetry (DEXA), tail bleeding time, prothrombin time (PT), activated partial thromboplastin time (aPTT), serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) levels, aorta and serum cyclic guanosine monophosphate (cGMP), nitric oxide (NO) and endothelin (ET)-1 levels, aorta phosphorylated PI3K (pPI3K), phosphorylated Akt (pAkt) and phosphorylated p38 MAPK (pp38 MAPK) levels were systemically analyzed. In addition, aorta vascular dilation and constriction related gene mRNA expressions - PI3K, Akt, eNOS, p38 MAPK and ET-1 were also analyzed by realtime RT-PCR. Results : The obesity and related blood flow impairment, induced by 84 days of continuous HFD supply, were significantly inhibited by 56 days of continuous oral treatment of GBe 150, 100 and 50 mg/kg, dose-dependently, and they also dramatically normalized the changes of the aorta vascular dilation and constriction related gene mRNA expressions, also dose-dependently. Especially, GBe 150 mg/kg constantly showed favorable inhibitory activities against type II diabetes related obesity and vascular disorders through PI3K/Akt pathway and p38 MAPK mediated cGMP, NO and ET-1 expression modulatory activities, as comparable to those of metformin 250 mg/kg in HFD mice. Conclusion : By assessing the key parameters for anti-obese and blood flow improvement activities on the HFD-induced mild diabetic obese mice, the present work demonstrated that GBe 150, 100 and 50 mg/kg showed favorable anti-obese and blood flow improvement effects in HFD-induced type II diabetic mice, through PI3K/Akt pathway and p38 MAPK mediated cGMP, NO and ET-1 expression modulatory activities.
참고문헌 (85)
- Wendel AA, "Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob", ob mice, 2008, pp.49(1), 98~106
- Tilg H, "Adipocytokines: mediators linking adipose tissue, inflammation and immunity", Nature reviews Immunology, 6(10), pp.772~783 (2006)[DOI]
- James PT, "The Worldwide Obesity Epidemic", Obesity Research, 9(Suppl 4), pp.228S~233S (2001)[DOI]
- Zimmet P, "The burden of type 2 diabetes: are we doing enough?", Diabetes & metabolism, 29(4), pp.6S9~6S18 (2003)
- Kunitomi M, "Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men", International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 26(3), pp.361~369 (2002)[DOI]
- Hida K, "Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity", Proceedings of the National Academy of Sciences of the United States of America, 102(30), pp.10610~10615 (2005)
- Zhou M, "Shen-Yuan-Dan Capsule Inhibiting Inflammatory Reaction by Regulating Insulin Receptor Substrate 1", PI3K, NF-kB Signaling Pathway in Apoliprotein E Knockout Mice Fed with a High-Fat Diet, pp.Acta Cardiologica Sinica, 2017[DOI]
- Lloyd-Jones D, "Heart disease and stroke statistics -2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee", Circulation, 119(3), pp.480~486 (2009)[DOI]
- Kao YT, "Arterial Stiffness Index and Coronary Artery Plaques in Patients with Subclinical Coronary Atherosclerosis", Acta Cardiologica Sinica, 31(1), pp.59~65 (2015)
- Xie W, "MicroRNA-27 Prevents Atherosclerosis by Suppressing Lipoprotein Lipase-Induced Lipid Accumulation and Inflammatory Response in Apolipoprotein E Knockout Mice", PloS one, 11(6), pp.e0157085~ (2016)[DOI]
- Glass CK, "Atherosclerosis. the road ahead", Cell, 104(4), pp.503~516 (2001)[DOI]
- Tabas I, "Apoptosis and plaque destabilization in atherosclerosis: the role of macrophage apoptosis induced by cholesterol", Cell death and differentiation, 11(Suppl 1), pp.S12~S16 (2004)[DOI]
- Pennings M, "Regulation of cholesterol homeostasis in macrophages and consequences for atherosclerotic lesion development", FEBS letters, 580(23), pp.5588~5596 (2006)[DOI]
- Kadowaki T, "Adiponectin and adiponectin receptors", Endocrine reviews, 26(3), pp.439~451 (2005)[DOI]
- Lorenzi M, "Pathobiology of endothelial and other vascular cells in diabetes mellitus. Call for data", Diabetes, 40(6), pp.653~659 (1991)[DOI]
- Cohen RA, "Dysfunction of vascular endothelium in diabetes mellitus", Circulation, 87(5S), pp.V67~V76 (1993)
- Oelze M, "Nebivolol inhibits superoxide formation by NADPH oxidase and endothelial dysfunction in angiotensin II-treated rats", Hypertension, 48(4), pp.677~684 (2006)[DOI]
- Oelze M, "Vasodilatorstimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric oxide", cGMP signaling and endothelial dysfunction, 2000, pp.87(11), 999~1005
- Jay D, "Oxidative stress and diabetic cardiovascular complications", Free radical biology & medicine, 40(2), pp.183~192 (2006)[DOI]
- Oelze M, "The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetesinduced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity", PloS one, 9(11), pp.e112394~ (2014)[DOI]
- Attele AS, "Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component", Diabetes, 51(6), pp.1851~1858 (2002)[DOI]
- Wang CZ, "Steamed American ginseng berry: ginsenoside analyses and anticancer activities", Journal of agricultural and food chemistry, 54(26), pp.9936~9942 (2006)[DOI]
- 배혜민, "Inhibitory Effects of Ginsenoside Re Isolated from Ginseng Berry on Histamine and Cytokine Release in Human Mast Cells and Human Alveolar Epithelial Cells", Journal of Ginseng Research, 36(4), pp.369~374 (2012), 고려인삼학회
- Lee DI, "Ginsenoside-free molecules from steam-dried ginseng berry promote ethanol metabolism: an alternative choice for an alcohol hangover", Journal of food science, 79(7), pp.C1323~C1330 (2014)[DOI]
- Dey L, "Anti-diabetic and anti-obese effects of ginseng berry extract: comparison between intraperitoneal and oral administrations", The American journal of Chinese medicine, 30(4), pp.645~647 (2002)[DOI]
- Xie JT, "Effects of American ginseng berry extract on blood glucose levels in ob", ob mice, 2002, pp.30(2-3), 187~194
- Xie JT, "American ginseng berry juice intake reduces blood glucose and body weight in ob", ob mice, 2007, pp.72(8), S590~S594
- Wang W, "In vitro anti-cancer activity and structure-activity relationships of natural products isolated from fruits of Panax ginseng", Cancer chemotherapy and pharmacology, 59(5), pp.589~601 (2007)[DOI]
- Shao ZH, "Antioxidant effects of American ginseng berry extract in cardiomyocytes exposed to acute oxidant stress", Biochimica et biophysica acta, 1670(3), pp.165~171 (2004)[DOI]
- Mehendale SR, "Chronic pretreatment with American ginseng berry and its polyphenolic constituents attenuate oxidant stress in cardiomyocytes", European journal of pharmacology, 553(1-3), pp.209~214 (2006)[DOI]
- Xie JT, "Antioxidant effects of ginsenoside Re in cardiomyocytes", European journal of pharmacology, 532(3), pp.201~207 (2006)[DOI]
- Zhang SC, "The anti-stress effect of saponins extracted from panax ginseng fruit and the hypophyseal-adrenal system", Yao xue xue bao = Acta pharmaceutica Sinica, 16(11), pp.860~863 (1981)
- Sena Lee, "Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48", 80, 2014, pp.38(2), 89~96[DOI]
- 김민희, "The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet", Journal of Ginseng Research, 41(2), pp.120~126 (2017), 고려인삼학회[DOI]
- Choi JS, "Blood glycemia-modulating effects of melanian snail protein hydrolysates in mice with type II diabetes", International journal of molecular medicine, 39(6), pp.1437~1451 (2017)[DOI]
- Kim MR, "Anti-obesity effects of yellow catfish protein hydrolysate on mice fed a 45% kcal high-fat diet", International journal of molecular medicine, 40(3), pp.784~800 (2017)[DOI]
- van Haare J, "Metformin and sulodexide restore cardiac microvascular perfusion capacity in diet-induced obese rats", Cardiovascular diabetology, 16(1), pp.47~ (2017)[DOI]
- Lee JE, "Fermentation of Green Tea with 2% Aquilariae lignum Increases the Anti-Diabetic Activity of Green Tea Aqueous Extracts in the High Fat-Fed Mouse", Nutrients, 7(11), pp.9046~9078 (2015)[DOI]
- 구세광, "Antithrombotic activities of sulforaphane via inhibiting platelet aggregation and FIIa", FXa, 2014, pp.37(11), 1454~1463[DOI]
- 윤은경, "Antitcoagulant and antiplatelet activities of scolymoside", BMB Reports, 48(10), pp.577~582 (2015), 생화학분자생물학회
- Barton M, "Obesity is associated with tissuespecific activation of renal angiotensin-converting enzyme in vivo: evidence for a regulatory role of endothelin", Hypertension, 35(1), pp.329~336 (2000)[DOI]
- Adiarto S, "Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by leptin", Biochemical and biophysical research communications, 353(3), pp.623~627 (2007)[DOI]
- Li T, "Effects of spinach nitrate on insulin resistance, endothelial dysfunction markers and inflammation in mice with high-fat and high-fructose consumption", Food & nutrition research, 60, pp.32010~ (2016)[DOI]
- Lowry OH, "Protein measurement with the Folin phenol reagent", The Journal of biological chemistry, 193(1), pp.265~275 (1951)
- Hogan MF, "Markers of Islet Endothelial Dysfunction Occur in Male B6.BKS(D)-Leprdb", J Mice and May Contribute to Reduced Insulin Release, 2017, pp.158(2), 293~303
- Schmittgen TD, "Analyzing realtime PCR data by the comparative CT method", Nature protocols, 3(6), pp.1101~1108 (2008)[DOI]
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the <TEX>$2^{-DDCt}$<", TEX> Method, 2001, pp.25(4), 402~408
- Kim CM, "Red-koji fermented red ginseng ameliorates high fat diet-induced metabolic disorders in mice", Nutrients, 5(11), pp.4316~4332 (2013)[DOI]
- Kang SJ, "Fermentation with Aquilariae Lignum enhances the anti-diabetic activity of green tea in type II diabetic db", db mouse, 2014, pp.6(9), 3536~3571
- Mitchell M, "Adipokines: implications for female fertility and obesity", Reproduction, 130(5), pp.583~597 (2005)[DOI]
- Mazur-Bialy AI, "Beneficial Effect of Voluntary Exercise on Experimental Colitisin Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers", Nutrients, 9(4) (2017)
- Anfossi G, "Platelet dysfunction in central obesity", Nutrition, metabolism, and cardiovascular diseases : NMCD, 19(6), pp.440~449 (2009)[DOI]
- Mertens I, "Obesity, haemostasis and the fibrinolytic system", Obesity reviews : an official journal of the International Association for the Study of Obesity, 3(2), pp.85~101 (2002)[DOI]
- Nagai N, "Obesity promotes injury induced femoral artery thrombosis in mice", Thrombosis research, 122(4), pp.549~555 (2008)[DOI]
- Rosito GA, "Association between obesity and a prothrombotic state: the Framingham Offspring Study", Thrombosis and haemostasis, 91(4), pp.683~689 (2004)
- Lyon CJ, "Minireview: adiposity, inflammation, and atherogenesis", Endocrinology, 144(6), pp.2195~2200 (2003)[DOI]
- Chen L, "Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia", Frontiers in physiology, 9, pp.197~ (2018)[DOI]
- Valenta I, "Impact of Obesity and Bariatric Surgery on Metabolism and Coronary Circulatory Function", Current Cardiology Reports, 16(1), pp.433~ (2013)
- Tousoulis D, "Inflammatory and thrombotic mechanisms in coronary atherosclerosis", Heart, 89(9), pp.993~997 (2003), British Cardiac Society[DOI]
- Kaye SM, "Obesityrelated derangements of coagulation and fibrinolysis: a study of obesitydiscordant monozygotic twin pairs", Obesity, 20(1), pp.88~94 (2012)[DOI]
- Kaji N, "Shortened blood coagulation times in genetically obese rats and dietinduced obese mice", The Journal of veterinary medical science, 75(9), pp.1245~1248 (2013)[DOI]
- Yamamoto Y, "The effect of the long term aspirin administration on the progress of atherosclerosis in apoE-", - LDLR-, Thrombosis research, pp.2010, 125(3)[DOI]
- Xie W, "Free fatty acids inhibit TM-EPCR expressionthrough JNK pathway: an implication for the development of the prothrombotic state in metabolic syndrome", Journal of thrombosis and thrombolysis, 34(4), pp.468~474 (2012)[DOI]
- Chen H, "Physicochemical properties and antioxidant capacity of 3 polysaccharides from green tea, oolong tea, and black tea", Journal of food science, 74(6), pp.C469~C474 (2009)[DOI]
- Sansbury BE, "Regulation of obesity and insulin resistance by nitric oxide", Free radical biology & medicine, 73, pp.383~399 (2014)[DOI]
- Rudyk O, "Examining a role for PKG Iaoxidation in the pathogenesis of cardiovascular dysfunction during diet-induced obesity", Free radical biology & medicine, 110, pp.390~398 (2017)[DOI]
- Yanagisawa M, "A novel potent vasoconstrictor peptide produced by vascular endothelial cells", Nature, 332(6163), pp.411~415 (1988)[DOI]
- Ishida F, "Suppressive effects of the endothelin receptor (ETA) antagonist BQ-123 on ET-1-induced reduction of lipoprotein lipase activity in 3T3-L1 adipocytes", Biochemical pharmacology, 44(7), pp.1431~1436 (1992)[DOI]
- Uchida Y, "Endothelin-1, but not endothelin-3, suppresses lipoprotein lipase gene expression in brown adipocytes differentiated in culture", European journal of pharmacology, 291(1), pp.33~41 (1995)[DOI]
- Parrinello G, "Central obesity and hypertension: the role of plasma endothelin", American journal of hypertension, 9(12), pp.1186~1191 (1996)[DOI]
- Tiret L, "The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people", Hypertension, 33(5), pp.1169~1174 (1999)[DOI]
- Muniyappa R, "Cardiovascular actions of insulin", Endocrine reviews, 28(5), pp.463~491 (2007)[DOI]
- Cardillo C, "Insulin stimulates both endothelin and nitric oxide activity in the human forearm", Circulation, 100(8), pp.820~825 (1999)[DOI]
- Zeng G, "Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells", Circulation, 101(13), pp.1539~1545 (2000)[DOI]
- Eringa EC, "Vasoconstrictor effects of insulin in skeletal muscle arterioles are mediated by ERK1", 2 activation in endothelium, 2004, pp.287(5), H2043~H2048
- Huang PL, "eNOS, metabolic syndrome and cardiovascular disease", Trends in endocrinology and metabolism: TEM, 20(6), pp.295~302 (2009)[DOI]
- Ko SH, "Hypertension management and microvascular insulin resistance in diabetes", Current hypertension reports, 12(4), pp.243~251 (2010)[DOI]
- Bourgoin F, "Endothelial and vascular dysfunctions and insulin resistance in rats fed a high-fat, highsucrose diet", American journal of physiology Heart and circulatory physiology, 295(3), pp.H1044~H1055 (2008)[DOI]
- Wang Y, "APPL1 counteracts obesity-induced vascular insulin resistance and endothelial dysfunction by modulating the endothelial production of nitric oxide and endothelin-1 in mice", Diabetes, 60(11), pp.3044~3054 (2011)[DOI]
- Li J, "The Protective Effect of Beraprost Sodium on Diabetic Cardiomyopathy through the Inhibition of the p38 MAPK Signaling Pathway in High-Fat-Induced SD Rats", International journal of endocrinology, 2014, pp.901437~ (2014)
- Chen S, "A role for p38 mitogen-activated protein kinase and c-myc in endothelin-dependent rat aortic smooth muscle cell proliferation", Hypertension, 47(2), pp.252~258 (2006)[DOI]
- Soldatos G, "Diabetic nephropathy: important pathophysiologic mechanisms", Diabetes research and clinical practice, 82(Suppl 1), pp.S75~S79 (2008)[DOI]
- Sato S, "Halofuginone prevents extracellular matrix deposition in diabetic nephropathy", Biochemical and biophysical research communications, 379(2), pp.411~416 (2009)[DOI]
- Carta L, "p38 MAPK is an early determinant of promiscuous Smad 2", 3 signaling in the aortas of fibrillin-1 (Fbn1)-null mice, 2009, pp.284(9), 5630~5636
- Wang Z, "Butein induction of HO-1 by p38 MAPK", Nrf2 pathway in adipocytes attenuates high-fat diet induced adipose hypertrophy in mice, 2017, pp.799, 201~210
