동과자 에탄올 추출물이 비알코올성 지방간 세포 모델에 미치는 효과
Effects of Ethanol Extract of Benincasa Seeds on the Experimental Cellular Model of Nonalcoholic Fatty Liver Disease
2
조회
0
다운로드
6
인용
0
참고문헌
키워드
초록
Objectives : In this study, we investigated the effect and the underlying mechanism of ethanol extract of Benincasa Seeds on a cellular model of non-alcoholic fatty liver disease (NAFLD) established by treating HepG2 cells with palmitate. Methods : We evaluated ethanol extract of Benincasa Seeds (EEBS) for their hepatic lipid-lowering potential in fatty acid overloaded HepG2 cells. After incubation in palmitate containing media with or without EEBS, intracellular neutral lipid accumulation were quantified by Nile Red staining. We also investigated the effect of EEBS on lipogenesis and β-oxidation. LXRα-dependent SREBP-1c activation, expression of lipogenic genes, and expression of β-oxidation related genes were determined with or without pretreatment of EEBS. Results : EEBS significantly attenuated palmitate-induced intracellular neutral lipid accumulation in HepG2 cells. EEBS suppressed fatty acid synthesis by inhibiting LXRα-dependent SREBP-1c activation. EEBS also repressed SREBP-1c mediated induction of lipogenic genes, including ACC, FAS, and SCD-1. But, EEBS had no effect on β-oxidation related CPT-1 and PPARα gene expression. Conclusions : Our study suggestes that EEBS has an efficacy to decrease hepatic lipid accumulation, and this effect was mediated by inhibiting LXRα-SREBP-1c pathway that leads to expression of lipogenic genes and heatic steatosis. Therefore, the Benincasa seeds may be a potential clinical application for treatment of this chronic liver disease.
Abstract
Objectives : In this study, we investigated the effect and the underlying mechanism of ethanol extract of Benincasa Seeds on a cellular model of non-alcoholic fatty liver disease (NAFLD) established by treating HepG2 cells with palmitate. Methods : We evaluated ethanol extract of Benincasa Seeds (EEBS) for their hepatic lipid-lowering potential in fatty acid overloaded HepG2 cells. After incubation in palmitate containing media with or without EEBS, intracellular neutral lipid accumulation were quantified by Nile Red staining. We also investigated the effect of EEBS on lipogenesis and β-oxidation. LXRα-dependent SREBP-1c activation, expression of lipogenic genes, and expression of β-oxidation related genes were determined with or without pretreatment of EEBS. Results : EEBS significantly attenuated palmitate-induced intracellular neutral lipid accumulation in HepG2 cells. EEBS suppressed fatty acid synthesis by inhibiting LXRα-dependent SREBP-1c activation. EEBS also repressed SREBP-1c mediated induction of lipogenic genes, including ACC, FAS, and SCD-1. But, EEBS had no effect on β-oxidation related CPT-1 and PPARα gene expression. Conclusions : Our study suggestes that EEBS has an efficacy to decrease hepatic lipid accumulation, and this effect was mediated by inhibiting LXRα-SREBP-1c pathway that leads to expression of lipogenic genes and heatic steatosis. Therefore, the Benincasa seeds may be a potential clinical application for treatment of this chronic liver disease.
참고문헌 (34)
- Smith BW, "Non-alcoholic fatty liver disease", Crit Rev Clin Lab Sci, 48(3), pp.97~113 (2011)
- Marchesini G, "Association of nonalcoholic fatty liver disease with insulin resistance", Am J Med, 107(5), pp.450~455 (1999)
- Angulo P, "Nonalcoholic fatty liver disease", N Engl J Med, 346(16), pp.1221~1231 (2002)
- Sung TS, "Effect of Cnidi rhizoma boiling extract solution on enzyme and hormone of plasma, and liver in the fatted rats induced by high fat dietary", Korean J Food & Nutrition, 7(2), pp.108~113 (1994)
- 윤경수, "NASH 동물모델에서 인진청간탕과 인진사령산의 효과규명", 대한한방내과학회지, 30(2), pp.410~421 (2009), 대한한방내과학회
- 최미영, "加味生肝湯이 고지방식이로 유발된 지방간에 미치는 영향", 대한한방내과학회지, 30(2), pp.365~374 (2009), 대한한방내과학회
- 유재연, "지방산으로 유발된 비알코올지방간질환 실험모델에 미치는 生肝湯加味方의 효과", 대한한방내과학회지, 31(2), pp.331~345 (2010), 대한한방내과학회
- Wu JN, "An illustrated Chinese materia medica", pp.134~ (2005), Oxford University Press
- Nakashima M, "Nitric oxide-dependent hypotensive effects of wax gourd juice", J Ethnopharmacol, 138(2), pp.404~407 (2011)
- Huh J, "Donguibogam", pp.745~ (1999), Beobin Press
- Wang W, "Effect of haidonghua powder(HDHP) on hypothalamic obesity in rats", Zhongguo Zhong yao za zhi, 25(8), pp.490~492 (2000)
- Huang HY, "Antioxidant and angiotension-converting enzyme inhibition capacities of various parts of Benincasa hispida (wax gourd)", Die Nahrung, 48(3), pp.230~233 (2004)
- Patil RN, "Evaluation of antidiabetic and related actions of some Indian medicinal plants in diabetic rats", Asian Pac J Trop Med, 4(1), pp.20~23 (2011)
- Moon MK, "Effect of Benincasa hispida Cogniaux on high glucose-induced vascular inflammation of human umbilical vein endothelial cells", VASCULAR PHARMACOLOGY, 50, pp.116~122 (2009), ELSEVIER SCIENCE INC
- 박승하, "Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults", JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 21(1), pp.138~143, BLACKWELL PUBLISHING
- Marra F, "Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis", Trends Mol Med, 14(2), pp.72~81 (2008)
- Lewis GF, "Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes", Endocr Rev, 23(2), pp.201~229 (2002)
- Wahren J, "Turnover and splanchnic metabolism of free fatty acids and ketones in insulin- dependent diabetics at rest and in response to exercise", J Clin Invest, 73(5), pp.1367~1376 (1984)
- Chen G, "Central role for liver X receptor in insulin- mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver", Proc Natl Acad Sci U S A, 101(31), pp.11245~11250 (2004)
- Browning JD, "Molecular mediators of hepatic steatosis and liver injury", J Clin Invest, 114(2), pp.147~152 (2004)
- Pettinelli P, "Molecular mechanisms of steatosis in nonalcoholic fatty liver disease", Nutr Hosp, 26(3), pp.441~450 (2011)
- Bimakr M, "Optimization of Ultrasound-Assisted Extraction of Crude Oil from Winter Melon(Benincasa hispida) Seed Using Response Surface Methodology and Evaluation of Its Antioxidant Activity, Total Phenolic Content and Fatty Acid Composition", Molecules, 17(10), pp.11748~11762 (2012)
- Sabale V, "Formulation and in vitro evaluation of the topical antiageing preparation of the fruit of Benincasa hispida", J Ayurveda Integr Med, 2(3), pp.124~128 (2011)
- Qadrie ZL, "Antinociceptive and anti-pyretic activity of Benincasa hispida (thunb.) cogn. in Wistar albino rats", Pak J Pharm Sci, 22(3), pp.287~290 (2009)
- Mandal U, "Effect of different solvent extracts of Benincasa hispida T. on experimental hypochlorhydria in rat", J Adv Pharm Technol Res, 3(1), pp.41~46 (2012)
- Grover JK, "Extracts of Benincasa hispida prevent development of experimental ulcers", J Ethnopharmacol, 78(2), pp.159~164 (2001)
- Rachchh MA, "Gastroprotective effect of Benincasa hispida fruit extract", Indian J Pharmacol, 40(6), pp.271~275 (2008)
- Chandre R, "Clinical evaluation of Kushmanda Ghrita in the management of depressive illness", Ayu, 32(2), pp.230~233 (2011)
- Dhingra D, "Antidepressant-like activity of Benincasa hispida fruits in mice: Possible involvement of monoaminergic and GABAergic systems", J Pharmacol Pharmacother, 3(1), pp.60~62 (2012)
- Laffitte BA, "Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue", Proc Natl Acad Sci U S A, 100(9), pp.5419~5424 (2003)
- Repa JJ, "Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta", Genes Dev, 14(22), pp.2819~2830 (2000)
- Lee CH, "Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors", Endocrinology, 144(6), pp.2201~2207 (2003)
- Kersten S, "Peroxisome proliferator -activated receptor alpha mediates the adaptive response to fasting", J Clin Invest, 103(11), pp.1489~1498 (1999)
- McGarry JD, "Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes", Diabetes, 51(1), pp.7~18 (2002)
