Honokiol Metabolites Study in Rat Kidney Employing UHPLC-Q-TOF/MS and 13C Stable Isotope Labeling

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• 作者：Chunyan Wang (1) (2)
  Haoyu Ye (2)
  Minghai Tang (2)
  Li Wan (1)
  Neng Qiu (3)
  Xiaobin Li (1)
  Hairong Wang (1)
  Chunyu Wang (2)
  Lijuan Chen (2)
  
  1. School of Pharmacy ; Chengdu University of TCM ; The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine ; State Key Laboratory Breeding Base of Systematic Research ; Development and Utilization of Chinese Medicine Resources ; Chengdu ; 611137 ; China
  2. State Key Laboratory of Biotherapy ; West China Hospital ; West China Medical School ; Sichuan University ; Keyuan Road 4 ; Gaopeng Street ; Chengdu ; 610041 ; China
  3. Department of Bio-pharmaceutical Engineering ; School of Chemical Engineering ; Sichuan University ; Chengdu ; 610065 ; China
  
• 关键词：UHPLC ; Q ; TOF/MS ; Honokiol and 13C stable isotope ; Metabolites ; Rat kidney
• 刊名：Chromatographia
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：78
• 期：7-8
• 页码：507-514
• 全文大小：718 KB
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  3. Chang, KH, Yan, MD, Yao, CJ, Lin, PC, Lai, GM (2013) Honokiol-induced apoptosis and autophagy in glioblastoma multiforme cells. Oncol Lett 6: pp. 1435-1438
  4. Guillermo, RF, Santha, S, Stevens, J, Coughlin, E, Patel, P, Kaushik, RS, Dwivedi, C (2013) Honokiol inhibits tumor growth in a xenograft melanoma mice model and activates the apoptotic signaling pathway in vivo. Cancer Res.
  5. Steinmann, P, Walters, DK, Arlt, MJ, Banke, IJ, Ziegler, U, Langsam, B, Arbiser, J, Muff, R, Born, W, Fuchs, B (2012) Antimetastatic activity of honokiol in osteosarcoma. Cancer 118: pp. 2117-2127 CrossRef
  6. Nagalingam, A, Arbiser, J, Bonner, MY, Saxena, N, Sharma, D (2012) Honokiol, a promising small molecular weight natural agent, activates AMP-activated protein kinase in breast cancer cells via LKB1-dependent pathway and inhibits breast carcinogenesis. Cancer Res.
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  8. Li, W, Wang, Q, Su, Q, Ma, D, An, C, Ma, L, Liang, H (2014) Honokiol suppresses renal cancer cells鈥?metastasis via dual-blocking epithelial-mesenchymal transition and cancer stem cell properties through modulating miR-141/ZEB2 signaling. Mol Cells 37: pp. 383-388 CrossRef
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  21. B枚hmdorfer, M, Maier-Salamon, A, Taferner, B, Reznicek, G, Thalhammer, T, Hering, S, H眉fner, A, Sch眉hly, W, J盲ger, W (2011) In vitro metabolism and disposition of honokiol in rat and human livers. J Pharm Sci 100: pp. 3506-3516 CrossRef
  22. Liu, J, Tang, M, Lai, H, Dong, Y, Xie, C, Ye, H, Ma, L, Qiu, N, Li, Y, Cai, L, Chen, L (2013) Identification of metabolites of honokiol in rat urine using 13C stable isotope labeling and liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. J Chromatogr A 1295: pp. 48-56 CrossRef
  23. Lai, H, Tang, M, Liu, J, Dong, Y, Qiu, N, Li, S, Ma, L, Yang, J, Song, H, Zhang, Y, Peng, A, Chen, L (2013) Identification of honokiol metabolites in rats by the method of stable isotope cluster technique and ultra-high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. J Chromatogr B 931: pp. 157-163 CrossRef
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• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Analytical Chemistry
  Organic Chemistry
  Pharmacy
  Biochemistry
  Plant Sciences
  Measurement Science and Instrumentation
  
• 出版者：Vieweg Verlag
• ISSN：1612-1112

文摘

Kidneys are an important organ since they make a significant contribution to the metabolism and excretion of drugs in vivo. The aim of this study was to identity and tentatively elucidate honokiol metabolites in the rat kidney, after healthy rats were exposed to a 1:1 mixture of labeled 13C-honokiol and unlabeled honokiol, by ultra high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer platform. This platform is well known for its fast acquisition speed, superior sensitivity, high resolution, and excellent mass accuracy. Finally, a total of 19 metabolites belonging to phase II metabolites were identified tentatively by exact mass, and the fragmentation spectra of four metabolites are reported for the first reported time. Our results indicated that honokiol was metabolized via phase II biotransformation including sulfation, acetylation, glucuronidation and amino acid conjugation in rat kidney tissues. This is the first study focused on the honokiol biotransformation in the tissue of kidney, providing important details for a comprehensive standing of the metabolites of honokiol.