草莓提取物对脂肪酸合酶及脂肪细胞的抑制作用

doi:10.7523/j.issn.2095-6134.2010.6.006

摘要/Abstract

摘要：

脂肪酸合酶(FAS)是治疗肥胖症的潜在靶点.实验测定表明,草莓果肉渣及草莓叶的乙醇提取物再经乙酸乙酯萃取的有效组分对FAS具有强抑制作用,且分别对FAS的底物丙二酸单酰辅酶A、乙酰辅酶A呈非竞争性和竞争性抑制.经HPLC-MS分析,槲皮素和鞣花酸可能是草莓有效组分中起主要作用的物质.草莓叶及果肉渣乙酸乙酯提取组分均可有效抑制3T3-L1前脂肪细胞中脂滴积累,且呈剂量依赖性.实验结果对于研究草莓在防治肥胖症的应用上可能具有重要价值.

关键词: 脂肪酸合酶, 草莓, 抑制剂, 抑制动力学, 减肥

Abstract:

Fatty acid synthase (FAS) has been considered as a potential new therapeutic target for obesity. In the present study we show that the components of both strawberry ( Fragaria ananassa Duch) fruit dreg and strawberry leaves that extracted with 50% ethanol and partitioned by ethyl acetate are potent FAS inhibitors. The ethyl acetate fractions of strawberry fruit dregs (SF-AE) show noncompetitive inhibition with the substrate Mal-CoA, while the ethyl acetate fractions of strawberry leaves (SL-AE) show competitive inhibition with Ac-CoA. Based on the HPLC-MS analysis, we conclude that ellagic acid and quercetin are the efficient components. SF-AE and SL-AE could reduce lipids accumulation in 3T3-L1 preadipocyte with dose-dependence. These results may be of great value for application of strawberry extracts to obesity prevention and cure.

Key words: fatty acid synthase, strawberry, inhibitor, kinetic assay, anti-obesity

中图分类号:

R285.5

刘晓鑫, 田维熙, 马晓丰. 草莓提取物对脂肪酸合酶及脂肪细胞的抑制作用[J]. 中国科学院大学学报, 2010, 27(6): 768-777.

LIU Xiao-Xin, TIAN Wei-Xi, MA Xiao-Feng. Inhibitory effects of strawberry extracts on animal fatty acid synthase[J]. , 2010, 27(6): 768-777.

参考文献

[1] Tian W X. The control of animal fat level and fatty acid synthase activity
[J]. Chemistry of Life, 1994, 14: 1-5 (in Chinese). 田维熙.动物的体脂水平和脂肪酸合成酶活性的调控
[J].生命的化学,1994,14(1):1-5.

[2] Li M, Shi Y, Tian W X. Factors influencing the levels of fatty acid synthase complex activity in fowl
[J]. Biochem Mol Biol Int, 1999, 47(1): 63-69.

[3] Tian W X, Dong Y, Quan H,et al. The dependence of fat level of hen on activity of fatty acid synthase in lever on different ages
[J]. Chinese Biochemical Journal, 1996, 12: 234-236 (in Chinese). 田维熙,董妍,权晖,等.不同生长期蛋鸡的体脂水平和肝脏脂肪酸合成酶活性的关系
[J].生物化学杂志,1996,12(2):234-236.

[4] Loftus T M, Jaworsky D E, Frehywot G L, et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors
[J]. Science, 2000, 288(5475): 2379-2381.

[5] Flier J S. The adipocyte: storage depot or node on the energy information superhighway?
[J]. Cell, 1995, 80(1): 15-18.

[6] Rosen E D. Molecular mechanisms of adipocyte differentiation
[J]. Ann Endocrinol (Paris), 2002. 63(1): 79- 82.

[7] Schmid B, Rippmann J F, Tadayyon M, et al. Inhibition of fatty acid synthase prevents preadipocyte differentiation
[J]. Biochem Biophys Res Commun, 2005, 328(4): 1073-1082.

[8] Daniel E M, Stoner G D. The effects of ellagic acid and 13-cis-retinoic acid on N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats
[J]. Cancer Lett, 1991, 56(2): 117-124.

[9] Shiow Y W. Inhibitory effect on activator protein-1, nuclear factor-kappa B, and cell transformation by extracts of strawberries (Fragaria ananassa Duch)
[J]. Agra Food Chem, 2005, 53(10): 4187- 4193.

[10] Tian W X, Wang Y S, Hsu R Y. Affinity labeling of chicken liver fatty acid synthase with chloroacetyl-CoA and bromopyruvate
[J]. Biochim Biophys Acta, 1989, 998(3): 310-316.

[11] Tian W X, Jiang R F, Wu H B, et al. The substrate inhibition by NADPH and kinetics of fatty acid synthase from duck liver
[J]. Chinese Biochemical Journa1, 1994, 10(4): 413- 419 (in Chinese). 田维熙,蒋若帆,吴海斌,等.鸭肝脂肪酸合成酶的NADPH底物抑制及作用动力学
[J].生物化学杂志,1994,10(4):413- 419.

[12] Seeram N P, Adams L S. Blackberry, black raspberry, blue berry, red raspberry, and strawberry extracts inhubit growth and stimulate apoptosis of human cancer cells in vitro
[J]. J Agric Food Chem, 2006, 54(25): 9329-9339.

[13] Wulf J S, Rühmann S, Rego I, et al. Nondestructive application of laser-induced fluorescence spectroscopy for quantitative analyses of phenolic compounds in strawberry fruits (Fragaria ananassa)
[J]. Agric Food Chem, 2008, 56(9): 2875-2882.

[14] Kati H, Ilana R, Harri K, et al. Non-targeted analysis of spatial metabolite composition in strawberry (Fragaria ananassa) flowers
[J]. Phytochemistry, 2008, 69(13): 2463-2481.

[15] Wang Y Y, Jiang G B, Hu W Z, et al. Determination of vitamin C in strawberry by high performance liquid chromatography
[J]. Journal of Dalian University, 2006, 27(1): 21-22 (in Chinese). 王艳颖,姜国斌,胡文忠,等.高效液相色谱法测定草莓中维生素C含量
[J].大连大学学报,2006,27(1):21-22.

[16] Seeram N P, Lee R, Scheuller H S, et al. Identification of phenolic compounds in strawberries by liquid chromatography electrospray ionization mass spectroscopy
[J]. Food Chem, 2006, 97(1): 1-11.

[17] Vasco C, Riihinen K, Ruales J, et al. Phenolic compounds in rosaceae fruits from ecuador
[J]. J Agric Food Chem, 2009, 57 (4): 1204-1212.

[18] Mudnic I, Modun D, Brizic I, et al. Cardiovascular effects in vitro of aqueous extract of wild strawberry (Fragaria vesca, L.) leaves
[J]. Phytomedicine, 2009, 16(5): 462- 469.

[19] Vance D, Goldberg I,Mitsuhashi O, et al. Inhibition of fatty acid synthetases by the antibiotic cerulenin
[J]. Biochem Bhys Res Commun, 1972, 48(3): 649- 656.

[20] Wang X, Tian W X. Green tea epigallocatechin gallate: a natural inhibitor of fatty acid synthase
[J]. Biochem Biophys Res Commun, 2001, 288(5): 1200-1206.

[21] Hannum S M. Potential impact of strawberries on human health: a review of the science
[J]. Crit Rev Food Sci Nutr, 2004, 44(1): 1-17.

[22] Gil M I, Holcroft D M, Kader A A. Changes in strawberry anthocyanins and other polyphenols in response to carbon dioxide treatments
[J]. J Agric Food Chem, 1997, 45(5): 1662-1667.

[23] Cordenunsi B R, Genovese M I, Nascimento J R O, et al. Effects of temperature on the chemical composition and antioxidant activity of three strawberry cultivars
[J]. Food Chem, 2005, 91(1): 113-121.

[24] Maas J L, Galletta G J. Ellagic acid, an anticarcinogen in fruits, especially in strawberry
[J]. Hortscience, 1991, 26(1): 10.

[25] Li B H, Tian W X. Inhibitory effects of flavonoids on animal fatty acid synthase
[J]. J Biochem, 2004, 135(1): 85-91.