Skip to main content
Log in

An application of target profiling analyses in the hepatotoxicity assessment of herbal medicines: comparative characteristic fingerprint and bile acid profiling of Senecio vulgaris L. and Senecio scandens Buch.-Ham

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

The toxicity assessment of herbal medicines is important for human health and appropriate utilization of these medicines. However, challenges have to be overcome because of the complexity of coexisting multiple components in herbal medicines and the highly interconnected organismal system. In this study, a target profiling approach was established by combining the characteristic fingerprint analysis of herbal chemicals with potential toxicity through a precursor ion scan-based mass spectroscopy and the target profiling analysis of biomarkers responsible for the toxicity. Through this newly developed approach, the comparative hepatotoxicity assessment of two herbal medicines from the same genus, Senecio vulgaris L. and Senecio scandens Buch.-Ham, was performed. Significant differences were found between the two species in their chemical markers (i.e., pyrrolizidine alkaloids) and biomarkers (i.e., bile acids) responsible for their toxicities. This result was consistent with the conventional toxicity assessment conducted by histopathological examination and clinical serum index assay on experimental animal models. In conclusion, this study provided a new approach for the hepatotoxicity assessment of herbal medicines containing pyrrolizidine alkaloids, which are widely distributed in various herbal medicines. The target profiling approach may shed light on the toxicity assessment of other herbal medicines with potential toxicity.

The comparative hepatotoxicity assessment of two herbal medicines, Senecio vulgaris L. (SV) and Senecio scandens Buch.-Ham (SS), was performed by combining the characteristic fingerprint analysis of toxic chemical markers (i.e. pyrrolizidine akaloids) through a precursor ion scan-based mass spectroscopy and the target profiling analysis of toxic biomarkers (i.e. bile acids). It was found that SV was highly hepatotoxic as they contained higher concentration of toxic chemicals, which induced significant changes in the bile acid profile by the transcriptional regulation of their synthesis, excretion, and uptake

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

Access this article

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
Fig. 6

Similar content being viewed by others

References

  1. Lv W, Piao JH, Jiang JG (2012) Expert Opin Drug Saf 11:985–1002

    Article  CAS  Google Scholar 

  2. Abdualmjid RJ, Sergi C (2013) J Pharm Pharm Sci 16:376–404

    Google Scholar 

  3. Vanherwegham JL, Depierreux M, Tielemans C, Abramowicz D, Dratwa M, Jadoul M, Richard C, Vandervelde D, Verbeelen D, Vanhaelen-Fastre R (1993) Lancet 341:387–391

    Article  Google Scholar 

  4. Ernst E (2003) Can J Cardiol 19:818–827

    CAS  Google Scholar 

  5. Chan TYK, Tam HP, Lai CK, Chan AYW (2005) Ther Drug Monit 27:53–57

    Article  Google Scholar 

  6. Seeff LB (2007) Clin Liver Dis 11:577–596

    Article  Google Scholar 

  7. Jordan SA, Cunningham DG, Marles RJ (2010) Toxicol Appl Pharmacol 243:198–216

    Article  CAS  Google Scholar 

  8. Shaw D (2010) Planta Med 76:2012–2018

    Article  CAS  Google Scholar 

  9. Efferth T, Kaina B (2011) Curr Drug Metab 12:989–996

    Article  CAS  Google Scholar 

  10. Ma B, Li N, Lin G (2012) Curr Drug Metab 13:652–658

    Article  CAS  Google Scholar 

  11. Chang WT, Thissen U, Ehlert KA, Koek MM, Jellema RJ, Hankemeier T, Van der Greef J, Wang M (2006) Planta Med 72:458–467

    Article  CAS  Google Scholar 

  12. Zhang Y, Li F, Huang F, Xie G, Wei R, Chen T, Liu J, Zhao A, Jia W (2014) J Sep Sci 37:731–737

    Article  CAS  Google Scholar 

  13. Roeder E (1995) Pharmazie 50:83–98

    CAS  Google Scholar 

  14. Roeder E (2000) Pharmazie 55:711–726

    CAS  Google Scholar 

  15. International Programme on Chemical Safety (1988) Pyrrolizidine alkaloids. Environmental health criteria 80.WHO, Geneva

  16. Xiong AZ, Yang L, He YQ, Zhang F, Wang J, Han H, Wang CH, Bligh SWA, Wang ZT (2009) Rapid Commun Mass Spectrom 23:3907–3916

    Article  CAS  Google Scholar 

  17. Zhou Y, Li N, Choi FF, Qiao CF, Song JZ, Li SL, Liu X, Cai ZW, Fu PP, Lin G, Xu HX (2010) Anal Chim Acta 681:33–40

    Article  CAS  Google Scholar 

  18. Ruan J, Li N, Xia Q, Fu PP, Peng S, Ye Y, Lin G (2012) J Mass Spectrom 47:331–337

    Article  CAS  Google Scholar 

  19. Qi M, Xiong AZ, Geng F, Yang L, Wang ZT (2012) J Sep Sci 35:1470–1478

    Article  CAS  Google Scholar 

  20. Ji S, Wang Q, Qiao X, Guo HC, Yang YF, Bo T, Xiang C, Guo DA, Ye M (2014) J Pharm Biomed Anal 90:15–26

    Article  CAS  Google Scholar 

  21. International Programme on Chemical Safety (1989) Pyrrolizidine alkaloids health and safety guide. Health and safety guide no. 26. WHO, Geneva

  22. Dai N, Yu YC, Ren TH, Wu JG, Jiang Y, Shen LG, Zhang J (2007) World J Gastroenterol 13:1628–1631

    Article  Google Scholar 

  23. Altaee MY, Mahmood MH (1998) East Mediterr Health J 4:142–148

    Google Scholar 

  24. Kakar F, Akbarian Z, Leslie T, Mustafa ML, Watson J, van Egmond HP, Omar MF, Mofleh J (2010) J Toxicol 2010:313280

    Article  Google Scholar 

  25. Bane A, Seboxa T, Mesfin G, Ali A, Tsegaye YW, Tensae MG, Selassie S, Haile T (2012) Eth Med J 50:9–16

    Google Scholar 

  26. Lewis CJ (2001) U.S. Food and Drug Administration Web site. http://www.fda.gov/Food/RecallsOutbreaksEmergencies/SafetyAlertsAdvisories/ucm111219.htm. Accessed 6 July 6 2001

  27. State Pharmacopoeia Commission of the P. R. China (2010) Pharmacopoeia of the People’s Republic of China 2010. China Medicinal Science and Technology Press, Beijing

    Google Scholar 

  28. Lessard P, Wilson WD, Olander HJ, Rogers QR, Mendel VE (1986) Am J Vet Res 47:1776–1780

    CAS  Google Scholar 

  29. Mendel VE, Witt MR, Gitchell BS, Gribble DN, Rogers QR, Segall HJ, Knight HD (1988) Am J Vet Res 49:572–578

    CAS  Google Scholar 

  30. Sutherland RJ, Deol HS, Hood PJ (1992) Vet Clin Pathol 21:51–56

    Article  Google Scholar 

  31. Yan CC, Huxtable RJ (1995) Toxicol Appl Pharmacol 130:132–139

    Article  CAS  Google Scholar 

  32. Xiong AZ, Yang F, Fang LX, Yang L, He YQ, Wan YY, Xu Y, Qi M, Wang XL, Yu K, Tsim KW, Wang ZT (2014) Chem Res Toxicol 27(5):775–786

    Article  CAS  Google Scholar 

  33. Chen J, Deng W, Wang J, Shao Y, Ou M, Ding M (2013) Int J Gynaecol Obstet 1:5–8

    Article  Google Scholar 

  34. Lake AD, Novak P, Shipkova P, Aranibar N, Robertson D, Reily MD, Lu Z, Lehman-McKeeman LD, Cherrington NJ (2013) Toxicol Appl Pharmacol 2:132–140

    Article  Google Scholar 

  35. Yang L, Xiong AZ, He YQ, Wang ZY, Wang CH, Wang ZT, Li W, Yang L, Hu ZB (2008) Chem Res Toxicol 21:2280–2288

    Article  CAS  Google Scholar 

  36. Yang F, Xu Y, Xiong AZ, He YQ, Yang L, Wan YJY, Wang ZT (2012) J Ethnopharmacol 144:599–604

    Article  CAS  Google Scholar 

  37. Ortiz Cansado A, Crespo Valadés E, Morales Blanco P, Sáenz de Santamaría J, González Campillejo JM, Ruiz Téllez T (1995) Gastroenterol Hepatol 18:413–416

    CAS  Google Scholar 

  38. Vilar JH, García M, Cabrera P (2000) Gastroenterol Hepatol 23:285–286

    CAS  Google Scholar 

  39. Li SL, Lin G, Fu PP, Chan CL, Li M, Jiang ZH, Zhao ZZ (2008) Rapid Commun Mass Spectrom 22:591–602

    Article  CAS  Google Scholar 

  40. Zhang F, Wang CH, Wang W, Chen LX, Ma HY, Zhang CF, Zhang M, Bligh SW, Wang ZT (2008) Phytochem Anal 19:25–31

    Article  CAS  Google Scholar 

  41. Jones AJ, Culvenor CCJ, Smith LW (1982) Aust J Chem 35(6):1173–1178

    Article  CAS  Google Scholar 

  42. Segall HJ, Dallas TL (1983) Phytochemistry 22(5):1271–1273

    Article  CAS  Google Scholar 

  43. Zalkow LH, Asibal CF, Glinski JA, Bonetti SJ, Gelbaum LT, VanDerveer D, Powis G (1988) J Nat Prod 51(4):690–702

    Article  CAS  Google Scholar 

  44. Witte L, Ernsta L, Wrayb V, Hartmann T (1992) Phytochemistry 31(3):1027–1028

    Article  CAS  Google Scholar 

  45. Noorwala M, Mohammad F, Ahmad V, Sener B, Ergun F, Deliorman D (2000) Fitoterapia 71(5):618–620

    Article  CAS  Google Scholar 

  46. Xiong AZ, Yang L, Ji LL, Wang ZY, Yang XJ, Chen Y, Wang XL, Wang CH, Wang ZT (2012) Metabolomics 8:614–623

    Article  CAS  Google Scholar 

  47. Wiklund S, Johansson E, Sjöström L, Mellerowicz EJ, Edlund U, Shockcor JP, Gottfries J, Moritz T, Trygg J (2008) Anal Chem 80:115–122

    Article  CAS  Google Scholar 

  48. Claudel R, Steals B, Kuipers F (2005) Arterioscler, Thromb, Vasc Biol 25:2020–2030

    Article  CAS  Google Scholar 

  49. Calkin AC, Tontonoz P (2012) Nat Rev Mol Cell Biol 13:213–224

    CAS  Google Scholar 

  50. Nicolaou M, Andress EJ, Zolnerciks JK, Dixon PH, Williamson C, Linton KJ (2012) J Pathol 226:300–315

    Article  CAS  Google Scholar 

  51. Wu XP, Chai J, Chen WS (2009) Acad J Sec Mil Med Univ 30:1398–1401

    CAS  Google Scholar 

  52. Abu-Hayyeh S, Papacleovoulou G, Lövgren-Sandblom A, Tahir M, Oduwole O, Jamaludin NA, Ravat S, Nikolova V, Chambers J, Selden C, Rees M, Marschall HU, Parker MG, Williamson C (2013) Hepatology 57:716–726

    Article  CAS  Google Scholar 

  53. Yang F, Huang X, Yi TS, Yen Y, Moore DD, Huang WD (2007) Cancer Res 67:863–867

    Article  CAS  Google Scholar 

  54. Pircher PC, Kitto JL, Petrowski ML, Tangirala RK, Bischoff ED, Schulman IG, Westin SK (2003) J Biol Chem 278(30):27703–27711

    Article  CAS  Google Scholar 

  55. Hadžić N, Bull LN, Clayton PT, Knisely AS (2012) World J Gastroenterol 18(25):3322–3326

    Google Scholar 

  56. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ (2000) Gastroenterology 118:422–430

    Article  CAS  Google Scholar 

  57. Cao J, Huang L, Liu Y, Hoffman T, Stieger B, Meier PJ, Vore M (2001) Hepatology 33:140–147

    Article  CAS  Google Scholar 

  58. Soroka CJ, Lee JM, Azzaroli F, Boyer JL (2001) Hepatology 33:783–791

    Article  CAS  Google Scholar 

  59. Teng S, Piquette-Miller M (2007) Br J Pharmacol 151:367–376

    Article  CAS  Google Scholar 

  60. Zollner G, Fickert P, Zenz R, Fuchsbichler A, Stumptner C, Kenner L, Ferenci P, Stauber RE, Krejs GJ, Denk H, Zatloukal K, Trauner M (2004) Hepatology 33:633–646

    Article  Google Scholar 

  61. Geier A, Dietrich CG, Gerloff T, Haendly J, Kullak-Ublick GA, Stieger B, Meier PJ, Matern S, Gartung C (2003) Biochim Biophys Acta 1609:87–94

    Article  CAS  Google Scholar 

  62. DeLeve LD, McCuskey RS, Wang X, Hu L, McCuskey MK, Epstein RB, Kanel GC (1999) Hepatology 29:1779–1791

    Article  CAS  Google Scholar 

  63. Lin G, Wang JY, Li N, Li M, Gao H, Ji Y, Zhang F, Wang H, Zhou Y, Ye Y, Xu HX, Zheng J (2011) J Hepatol 54:666–673

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the Program for Changjiang Scholars and Innovative Research Team in University (IRT1071), the National Nature Science Foundation of China (81222053), the Program for New Century Excellent Talents in University (NCET-12-1056), the Shanghai Nature Science Foundation (12ZR1450300), the Rising-Star Scholar Project of Shanghai Municipal Science and Technology Commission (12QH1402200), the Foundation for University Key Teacher of Shanghai Municipal Science and Technology (12CG50), the Foundation for University Young Teachers of Shanghai Municipal Education Commission (ZZSZY12014), the Hong Kong Scholars Program (XJ2012031), and the China Postdoctoral Science Foundation funded project (2012 T50451).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Li Yang or Zhengtao Wang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 171 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiong, A., Fang, L., Yang, X. et al. An application of target profiling analyses in the hepatotoxicity assessment of herbal medicines: comparative characteristic fingerprint and bile acid profiling of Senecio vulgaris L. and Senecio scandens Buch.-Ham. Anal Bioanal Chem 406, 7715–7727 (2014). https://doi.org/10.1007/s00216-014-8175-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-014-8175-z

Keywords

Navigation