Skip to main content
SpringerLink
Log in

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

  • Original
  • Published:
Chromatographia Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Vaid M, Sharma SD, Katiyar SK (2010) Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis by targeting UVB-induced inflammatory mediators and cell cycle regulators: development of topical formulation. Carcinogenesis 31(11):2004–2011

    Article  CAS  Google Scholar 

  2. Chen L, Zhang Q, Yang G, Fan L, Tang J, Garrard I, Ignatova S, Fisher D, Sutherland IA (2007) Rapid purification and scale-up of honokiol and magnolol using high-capacity high-speed counter-current chromatography. J Chromatogr A 1142(2):115–122

    Article  CAS  Google Scholar 

  3. Chang KH, Yan MD, Yao CJ, Lin PC, Lai GM (2013) Honokiol-induced apoptosis and autophagy in glioblastoma multiforme cells. Oncol Lett 6(5):1435–1438

    CAS  Google Scholar 

  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. doi:10.1158/1538-7445

    Google Scholar 

  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(8):2117–2127

    Article  CAS  Google Scholar 

  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. doi:10.1158/1538-7445

    Google Scholar 

  7. Chilampalli S, Averineni R, Xie JS, Perumal O, Dwivedi C (2011) Development of honokiol for the prevention of UVB-induced skin tumor development. Cancer Res. doi:10.1158/1538-7445

    Google Scholar 

  8. Li W, Wang Q, Su Q, Ma D, An C, Ma L, Liang H (2014) Honokiol suppresses renal cancer cells’ metastasis via dual-blocking epithelial-mesenchymal transition and cancer stem cell properties through modulating miR-141/ZEB2 signaling. Mol Cells 37(5):383–388

    Article  CAS  Google Scholar 

  9. Scheepstra M, Nieto L, Hirsch AK, Fuchs S, Leysen S, Lam CV, in hetPanhuis L, van Boeckel CA, Wienk H, Boelens R, Ottmann C, Milroy LG, Brunsveld L (2014) A natural-product switch for a dynamic protein interface. Angew Chem Int Ed 53(25):6443–6448

    Article  CAS  Google Scholar 

  10. Wu JP, Zhang W, Wu F, Zhao Y, Cheng LF, Xie JJ, Yao HP (2010) Honokiol: an effective inhibitor of high-glucose-induced up regulation of inflammatory cytokine production in human renal mesangial cells. Inflamm Res 59(12):1073–1079

    Article  CAS  Google Scholar 

  11. Li D, Xue R, Li Z, Chen M, Jiang W, Huang C (2014) In vivo metabolism study of Timosapon in BIII in rat using HPLC-QTOF-MS/MS. Chromatographia 77(11–12):853–858

    Article  CAS  Google Scholar 

  12. Huang M, Choo LW, Ho PC (2008) Characterization of metabolites of meisoindigo in male and female rat kidney microsomes by high-performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 22(23):3835–3845

    Article  CAS  Google Scholar 

  13. Lohr JW, Willsky GR, Acara MA (1998) Renal drug metabolism. Pharmacol rev 50(1):107–142

    CAS  Google Scholar 

  14. Imaoka S, Nagashima K, Funae Y (1990) Characterization of three cytochrome P450s purified from renal microsomes of untreated male rats and comparison with human renal cytochrome P450. Arch Biochem Biophys 276(2):473–480

    Article  CAS  Google Scholar 

  15. Fraser DR, Kodicek E (1970) Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nutr Rev 39(5):215–218

    Article  Google Scholar 

  16. Fraser D, Kooh SW, Kind HP, Holick MF, Tanaka Y, DeLuca HF (1973) Pathogenesis of hereditary vitamin-D-dependent rickets: an inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1α,25-dihydroxyvitamin D. New Engl J Med 289(16):817–822

    Article  CAS  Google Scholar 

  17. Anders MW (1980) Metabolism of drugs by the kidney. Kidney Int 18(5):636–647

    Article  CAS  Google Scholar 

  18. Redegeld FA, Hofman GA, Noordhoek J (1988) Conjugative clearance of 1-naphthol and disposition of its glucuronide and sulfate conjugates in the isolated perfused rat kidney. J Pharmacol Exp Ther 244(1):263–267

    CAS  Google Scholar 

  19. Quebbemann AJ, Anders MW (1973) Renal tubular conjugation and excretion of phenol and p-nitropiienol in the chicken: differing mechanisms of renal transfer. J Pharmacol Exp Ther 184(3):695–708

    CAS  Google Scholar 

  20. Diamond GL, Quebbemann AJ (1981) In vivo quantification of renal sulfate and glucuronide conjugation in the chicken. Drug Metab Dispos 9(5):402–409

    CAS  Google Scholar 

  21. Böhmdorfer M, Maier-Salamon A, Taferner B, Reznicek G, Thalhammer T, Hering S, Hüfner A, Schühly W, Jäger W (2011) In vitro metabolism and disposition of honokiol in rat and human livers. J Pharm Sci 100(8):3506–3516

    Article  Google Scholar 

  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 1295:48–56

    Article  CAS  Google Scholar 

  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 931:157–163

    Article  CAS  Google Scholar 

  24. Dong Y, Tang M, Song H, Li R, Wang C, Ye H, Qiu N, Zhang Y, Chen L, Wei Y (2014) Characterization of metabolic profile of honokiol in rat feces using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and 13C stable isotope labeling. J Chromatogr B 953–954:20–29

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81374017 and 81402493).

Conflict of interest

There authors have declared no conflict of interest.

Author information

Author notes

    Authors and Affiliations

    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

      Chunyan Wang, Li Wan, Xiaobin Li & Hairong Wang

    2. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu, 610041, China

      Chunyan Wang, Haoyu Ye, Minghai Tang, Chunyu Wang & Lijuan Chen

    3. Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu, 610065, China

      Neng Qiu

    Authors
    1. Chunyan Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Haoyu Ye
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Minghai Tang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Li Wan
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Neng Qiu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xiaobin Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Hairong Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Chunyu Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Lijuan Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Minghai Tang.

    Additional information

    C. Wang and H. Ye contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (PDF 434 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Wang, C., Ye, H., Tang, M. et al. Honokiol Metabolites Study in Rat Kidney Employing UHPLC-Q-TOF/MS and 13C Stable Isotope Labeling. Chromatographia 78, 507–514 (2015). https://doi.org/10.1007/s10337-015-2859-1

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10337-015-2859-1

    Keywords

    Search

    Navigation