trans isomers found in Acorus tatarinowii Schott, were tested for their potential ability to modulate the expression and function of P-gp in Caco-2 cells. MTT assays revealed that both α-asarone and β-asarone significantly enhanced the vincristine-induced cytotoxicity to cells. β-Asarone was the most potent. Flow cytometry showed that α- and β-asarone increased Rhodamine 123 (Rh123) uptake and inhibited Rh123 efflux in Caco-2 cells in a concentration-dependent manner. Furthermore, P-gp expression and P-gp mRNA in cells were decreased by exposure to α- and β-asarone. In addition, β-asarone increased the inhibition of P-gp activity in cells more than α-asarone. Thus, α- and β-asarone effectively reversed MDR by inhibiting P-gp function and expression." />
Reversing P-glycoprotein-mediated multidrug resistance in vitro by α-asarone and β-asarone, bioactive cis-em class="a-plus-plus">trans isomers from
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  • 作者:Xue Meng (1)
    Sha Liao (1)
    Xueyan Wang (2)
    Shixiang Wang (1)
    Xinfeng Zhao (1)
    Pu Jia (1)
    Weijing Pei (2)
    Xiaopu Zheng (3)
    Xiaohui Zheng (1) (2)
  • 关键词:α ; Asarone ; β ; Asarone ; Caco ; 2 cells ; Cytotoxicity ; Flow cytometry ; Multidrug resistance ; P ; glycoprotein
  • 刊名:Biotechnology Letters
  • 出版年:2014
  • 出版时间:April 2014
  • 年:2014
  • 卷:36
  • 期:4
  • 页码:685-691
  • 全文大小:246 KB
  • 参考文献:1. Chaudhary PM, Mechetner EB, Roninson IB (1992) Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes. Blood 80:2735-739
    2. Chen H, Li WG, Zhang XB, Wang L, Xu TL, Wu DZ, Li Y (2013) Alpha-asarone from / Acorus gramineus alleviates epilepsy by modulating A-type gaba receptors. Neuropharmacology 65:1-1 CrossRef
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    9. Lee B, Choi Y, Kim H, Kim SY, Hahm DH, Lee HJ, Shim I (2003) Protective effects of methanol extract of / Acori graminei rhizoma and / Uncariae ramulus et Uncus on ischemia-induced neuronal death and cognitive impairments in the rat. Life Sci 74:435-50 CrossRef
    10. Liu J, Li C, Xing G, Zhou L, Dong M, Geng Y, Li X, Li J, Wang G, Zou D, Niu Y (2010) Beta-asarone attenuates neuronal apoptosis induced by beta amyloid in rat hippocampus. Yakugaku Zasshi 130:737-46 shi.130.737" target="_blank" title="It opens in new window">CrossRef
    11. Lucia MB, Cauda R, Landay AL, Malorni W, Donelli G, Ortona L (1995) Transmembrane P-glycoprotein (P-gp/P-170) in HIV infection: analysis of lymphocyte surface expression and drug-unrelated function. AIDS Res Hum Retrovir 11:893-01 CrossRef
    12. Okamura N, Hirai M, Tanigawara Y, Tanaka K, Yasuhara M, Ueda K, Komano T, Hori R (1993) Digoxin–cyclosporin A interaction: modulation of the multidrug transporter P-glycoprotein in the kidney. J Pharmacol Exp Ther 266:1614-619
    13. Tan B, Piwnica-Worms D, Ratner L (2000) Multidrug resistance transporters and modulation. Curr Opin Oncol 12:450-58 CrossRef
    14. Wang EJ, Casciano CN, Clement RP, Johnson WW (2001) Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun 289:580-85 CrossRef
    15. Wu QD, Fang YQ, Chen YZ, Kuan ZS, Wang SY, He YP (2005) Protective eEffects of volatile oil of / Acorus tatarinowii Schott and / β-asarone on cardiovascular system. Tradit Chin Drug Res Clin Pharmacol 4:244-47
    16. Yang K, Wu J, Li X (2008) Recent advances in the research of P-glycoprotein inhibitors. Biosci Trends 2:137-46
    17. Yang Y, Wang SX, Fang MF, Yang LJ, Meng X, Zheng XH (2012) Modulation of P-glycoprotein by benzaldehyde, vanillin and / β-asarone. Chin Tradit Pat Med 7:1364-366
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    19. Zuo HL, Yang FQ, Zhang XM, Xia ZN (2011) Separation of cis-and trans-asarone from / Acorus tatarinowii by preparative gas chromatography. J Anal Methods Chem 2012:1- CrossRef
  • 作者单位:Xue Meng (1)
    Sha Liao (1)
    Xueyan Wang (2)
    Shixiang Wang (1)
    Xinfeng Zhao (1)
    Pu Jia (1)
    Weijing Pei (2)
    Xiaopu Zheng (3)
    Xiaohui Zheng (1) (2)

    1. College of Life Sciences, Northwest University, No. 229, Taibai Northern Road, Mail Box 195#, Xi’an, 710069, China
    2. Key Lab for New Drugs Research of TCM in Shenzhen, Shenzhen, 518057, China
    3. First Hospital of Medical College, Xi’an Jiaotong University, Xi’an, 710061, China
  • ISSN:1573-6776
文摘
P-Glycoprotein (P-gp), an ATP-binding cassette transporter, plays an important role in multidrug resistance (MDR). α-Asarone and β-asarone, bioactive cis-em class="a-plus-plus">trans isomers found in Acorus tatarinowii Schott, were tested for their potential ability to modulate the expression and function of P-gp in Caco-2 cells. MTT assays revealed that both α-asarone and β-asarone significantly enhanced the vincristine-induced cytotoxicity to cells. β-Asarone was the most potent. Flow cytometry showed that α- and β-asarone increased Rhodamine 123 (Rh123) uptake and inhibited Rh123 efflux in Caco-2 cells in a concentration-dependent manner. Furthermore, P-gp expression and P-gp mRNA in cells were decreased by exposure to α- and β-asarone. In addition, β-asarone increased the inhibition of P-gp activity in cells more than α-asarone. Thus, α- and β-asarone effectively reversed MDR by inhibiting P-gp function and expression.

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