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

doi:10.5246/jcps.2012.06.074

Abstract

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

CLC Number:

R962.1

Supporting:

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.

References

[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.