花椒提取物调节固醇和脂多糖诱导的胆固醇积聚

doi:10.5246/jcps.2012.06.074

花椒提取物调节固醇和脂多糖诱导的胆固醇积聚

吴婷婷, 侯爱君, 洪臻怡, 朱依谆^*

1. 复旦大学药学院药理教研室, 上海 201203
2. 复旦大学药学院生药教研室, 上海 201203

收稿日期:2012-05-16 修回日期:2012-08-10 出版日期:2012-10-25 发布日期:2012-10-25
通讯作者: 朱依谆*

Extracts of Zanthoxylum bungeanum regulate cholesterol accumulation induced by sterols and LPS in vitro and in vivo

Tingting Wu, Aijun Hou, Zhenyi Hong, Yizhun Zhu^*

1. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
2. Department of Pharmacognosia, School of Pharmacy, Fudan University, Shanghai 201203, China

Received:2012-05-16 Revised:2012-08-10 Online:2012-10-25 Published:2012-10-25
Contact: Yizhun Zhu*

摘要/Abstract

摘要：

本研究旨在通过体内和体外实验探索花椒的石油醚、乙酸乙酯和正丁醇萃取物调节固醇类物质和脂多糖诱导的胆固醇积聚。通过测定总酚含量萃取物和DPPH清除率评价萃取物的抗氧化活性。在体外我们用25-羟胆固醇+胆固醇诱导HepG2细胞, 经PE、EtOAc、BuOH 预处理之后, 发现细胞总胆固醇含量和ApoB的分泌降低, SREBP2、HMGCR和ACAT的表达下调的同时CYP27A1、ABCA1和LDLR的表达上调。在体内我们用腹腔注射LPS诱导C57BL/6小鼠产生炎症, 血清TNF-α水平和促炎因子mRNA的检测结果发现EtOAc和BuOH组分有抗炎的作用。另外, BuOH萃取物能降低肝脏总胆固醇含量, 提高LXR-α、ABCA1的mRNA表达。通过活性追踪分离, 我们从EtOAc和BuOH两个组分中分离得到β-谷甾醇、芝麻素、桉脂素和syringaresinol-β-D-glucoside 4个化合物。

关键词: 花椒, 胆固醇代谢, 固醇, LPS, HepG2细胞, C57BL/6小鼠

Abstract: In this investigation, the effects of PE, EtOAc, and BuOH fractions from Zanthoxylum bungeanum on cholesterol accumulation induced by sterols and LPS were determined in vitro and in vivo. HepG2 cells induced by 25-hydroxychoelsterol and cholesterol were employed as cell model. After treatment with PE, EtOAC, or BuOH fractions, cellular total cholesterol and apolipoprotein B secretion were significantly reduced. In addition, compared with control group, expressions of SREBP2, HMGCR, and ACAT decreased, while CYP27A1, ABCA1, and LDLR levels increased. Cholesterol accumulation was also induced in C57BL/6 mice by LPS and the mice were used as the animal model. Determination of serum TNF-α level and hepatic mRNA expression of TNF-α, IL-6, iNOS, COX-2 revealed that EtOAc and BuOH fractions had anti-inflammatory effects. Furthermore, hepatic total cholesterol was reduced, accompanied by the elevation of LXR-α and ABCA1 gene expression in BuOH fraction treated mice. Since EtOAc and BuOH fractions were found active, bioassay-guided isolation was performed and β-sitosterol, eudesmin, sesamin and syringaresinol-β-D-glucoside were isolated from the fractions.

Key words: Zanthoxylum bungeanum, Cholesterol metabolism, Sterols, LPS, HepG2, C57BL/6

中图分类号:

R962.1

Supporting:

Foundation item: National Science and Technology Major Project (Grant No. 2012ZX09501001-003).
^*Corresponding author. Tel.: 86-21-54237077

吴婷婷, 侯爱君, 洪臻怡, 朱依谆^*. 花椒提取物调节固醇和脂多糖诱导的胆固醇积聚[J]. , DOI: 10.5246/jcps.2012.06.074.

Tingting Wu, Aijun Hou, Zhenyi Hong, Yizhun Zhu^*. Extracts of Zanthoxylum bungeanum regulate cholesterol accumulation induced by sterols and LPS in vitro and in vivo [J]. , DOI: 10.5246/jcps.2012.06.074.

参考文献

[1] Libby, P. Nature. 2002, 420, 868-874.
[2] Mullen, E.; Brown, R.M.; Osborne, T.F.; Shay, N.F. J. Nutr. 2004, 134, 2942-2947.
[3] Detmers, P.A.; Hernandez, M.; Mudgett, J.; Hassing, H.; Burton, C.; Mundt, S.; Chun, S.; Fletcher, D.; Card, D.J.; Lisnock, J.; Weikel, R.; Bergstrom, J.D.; Shevell, D.E.; Hermanowski-Vosatka, A.; Sparrow, C.P.; Chao, Y.S.; Rader, D.J.; Wright, S.D.; Pure, E. J. Immunol. 2000, 165, 3430-3435.
[4] Kuhlencordt, P.J.; Chen, J.; Han, F.; Astern, J.; Huang, P.L. Circulation. 2001, 103, 3099-3104.
[5] Barish, G.D.; Evans, R.M. TEM. 2004, 15, 158-165.
[6] Guo, T.; Deng, Y.X.; Xie, H.; Yao, C.Y.; Cai, C.C.; Pan, S.l.; Wang, Y.L. Fitoterapia. 2011, 82, 347-351.
[7] Pereira, S.S.; Lopes, L.S.; Marques, R.B.; Figueiredo, K.A.; Costa, D.A.; Chaves, M.H.; Almeida, F.R.C. J. Ethnopharmacol. 2010, 129, 227-231.
[8] Chu, C.Y.; Lee, H.J.; Chu, C.Y.; Yin, Y.F.; Tseng, T.H. Food Chem. Toxicol. 2009, 47, 1265-1271.
[9] Maxfield, F.R.; Tabas, I. Nature. 2005, 438, 612-621.
[10] Li, Q.; Liu, Z.; Guo, J.; Chen, J.; Yang, P.; Tian, J.; Sun, J.; Zong, Y.; Qu, S. Int. J. Mol. Med. 2009, 24, 459-464.
[11] Li, Y.; Schwabe, R.F.; DeVries-Seimon, T.; Yao, P.M.; Gerbod-Giannone, M.C.; Tall, A.R.; Davis, R.J.; Flavell, R.; Brenner, D.A.; Tabas, I. J. Biol. Chem. 2005, 280, 21763-21772.
[12] Dashti, N. J. Biol. Chem. 1992, 267, 7160-7169.
[13] Yee, W.L.; Wang, Q.; Agdinaoay, T.; Dang, K.; Chang, H.; Grandinetti, A.; Franke, A.A.; Theriault, A. Mol. Cell Biochem. 2002, 229, 85-92.
[14] Hardardottir, I.; Grunfeld, C.; Feingold, K.R. Curr. Opin. Lipidol. 1994, 5, 207-215.
[15] Feingold, K.R.; Hardardottir, I.; Memon, R.; Krul, E.J.; Moser, A.H.; Taylor, J.M.; Grunfeld, C. J. Lipid. Res. 1993, 34, 2147-2158.
[16] Feingold, K.R.; Spady, D.K.; Pollock, A.S.; Moser, A.H.; Grunfeld, C. J. Lipid. Res. 1996, 37, 223-228.
[17] Ainsworth, E.A.; Gillespie, K.M. Nat. Protoc. 2007, 2, 875-877.
[18] Wang, R.; Chen, P.; Jia, F.; Tang, J.; Ma, F. Int. J. Biol. Macromol. 2012, 50, 331-336.
[19] Wang, X.L.; Hay, A.E.; Matheeussen, A.; Gupta, M.P.; Hostettmann, K. Magn. Reson. Chem. 2011, 49, 184-189.
[20] Latip, J.; Hartley, T.G.; Waterman, P.G. Phytochemistry. 1999, 51, 107-110.
[21] Hsieh, T.J.; Lu, L.H.; Su, C.C. Biophys. Chem. 2005, 114, 13-20.
[22] Tanaka, M.; Jingami, H.; Otani, H.; Cho, M.; Ueda, Y.; Arai, H.; Nagano, Y.; Doi, T.; Yokode, M.; Kita, T. J. Biol. Chem. 1993, 268, 12713-12718.
[23] Osono, Y.; Woollett, L.A.; Herz, J.; Dietschy, J.M. J. Clin. Invest. 1995, 95, 1124-1132.
[24] Maron, D.J.; Fazio, S.; Linton, M.F. Circulation. 2000, 101, 207-213.
[25] Wellington, C.L.; Brunham, L.R.; Zhou, S.; Singaraja, R.R.; Visscher, H.; Gelfer, A.; Ross, C.; James, E.; Liu, G.; Huber, M.T.; Yang, Y.Z.; Parks, R.J.; Groen, A.; Fruchart-Najib, J.; Hayden, M.R. J. Lipid. Res. 2003, 44, 1470-1480.
[26] Edwards, P.A.; Kennedy, M.A.; Mak, P.A. Vasc. Pharmacol. 2002, 38, 249-256.
[27] Tam, S.P.; Mok, L.; Chimini, G.; Vasa, M.; Deeley, R.G. Am. J. Physiol. Cell Pharm. 2006, 291, 490-502.
[28] Chang, T.Y.; Chang, C.C.; Cheng, D. Annu. Rev. Biochem. 1997, 66, 613-638.
[29] Sammalkorpi, K.; Valtonen, V.; Kerttula, Y.; Nikkila, E.; Taskinen, M.R. Metabolism. 1988, 37, 859-865.
[30] Hardardottir, I.; Moser, A.H.; Fuller, J.; Fielding, C.; Feingold, K.; Grunfeld, C. J. Clin. Invest. 1996, 97, 2585-2592.
[31] Khovidhunkit, W.; Memon, R.A.; Feingold, K.R.; Grunfeld, C. J. Infect. Dis. 2000, 181, 462-472.
[32] Joseph, S.B.; Castrillo, A.; Laffitte, B.A.; Mangelsdorf, D.J.; Tontonoz, P. Nat. Med. 2003, 9, 213-219.
[33] Khovidhunkit, W.; Moser, A.H.; Shigenaga, J.K.; Grunfeld, C.; Feingold, K.R. J. Lipid Res. 2003, 44, 1728-1736.
[34] Hwang, S.L.; Kim, H.N.; Jung, H.H.; Kim, J.E.; Choi, D.K.; Hur, J.M.; Lee, J.Y.; Song, H.; Song, K.S.; Huh, T.L. Biochem. Biophys. Res. Commun. 2008, 377, 1253-1258.
[35] Ide, T.; Ashakumary, L.; Takahashi, Y.; Kushiro, M.; Fukuda, N.; Sugano, M. BBA. 2001, 1534, 1-13.