Advertisement

Frontiers of Medicine

, Volume 9, Issue 4, pp 457–467 | Cite as

Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum

  • Jiabo Wang
  • Zhijie Ma
  • Ming Niu
  • Yun Zhu
  • Qingsheng Liang
  • Yanling Zhao
  • Jingyuan Song
  • Zhaofang Bai
  • Yaming Zhang
  • Ping Zhang
  • Na Li
  • Yakun Meng
  • Qi Li
  • Lushan Qin
  • Guangju Teng
  • Junling Cao
  • Baosen Li
  • Shilin Chen
  • Yonggang Li
  • Zhengsheng Zou
  • Honghao Zhou
  • Xiaohe Xiao
Research Article

Abstract

Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury (DILI) in the United States. However, reliable methods to identify the DILI causality of some herbs, such as Heshouwu (dried root of Polygonum multiflorum), remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% (9/40) and 30.6% (45/147) of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% (19/20) of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin (heavy metals, pesticides, and mycotoxins) contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.

Keywords

Polygonum multiflorum Chinese herbal medicine drug-induced liver injury pharmacognosy metabolomics stilbene 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

11684_2015_417_MOESM1_ESM.pdf (330 kb)
Supplementary material, approximately 330 KB.

References

  1. 1.
    Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ; Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014; 109(7): 950–966, quiz 967CrossRefPubMedGoogle Scholar
  2. 2.
    Danan G, Benichou C. Causality assessment of adverse reactions to drugs—I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993; 46(11): 1323–1330CrossRefPubMedGoogle Scholar
  3. 3.
    Maria VAJ, Victorino RMM. Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis. Hepatology 1997; 26(3): 664–669CrossRefPubMedGoogle Scholar
  4. 4.
    Rockey DC, Seeff LB, Rochon J, Freston J, Chalasani N, Bonacini M, Fontana RJ, Hayashi PH; US Drug-Induced Liver Injury Network. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the Roussel-Uclaf causality assessment method. Hepatology 2010; 51(6): 2117–2126PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Rochon J, Protiva P, Seeff LB, Fontana RJ, Liangpunsakul S, Watkins PB, Davern T, McHutchison JG; Drug-Induced Liver Injury Network (DILIN). Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury. Hepatology 2008; 48(4): 1175–1183PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Barritt AS, Lee J, Hayashi PH. Detective work in drug-induced liver injury: sometimes it is all about interviewing the right witness. Clin Gastroenterol Hepato, 2010, 8(7): 635–637CrossRefGoogle Scholar
  7. 7.
    de Smet PA. Herbal medicine in Europe—relaxing regulatory standards. N Engl J Med 2005; 352(12): 1176–1178CrossRefPubMedGoogle Scholar
  8. 8.
    Teschke R, Eickhoff A, Wolff A, Frenzel C, Schulze J. Herbal hepatotoxicity and WHO global introspection method. Ann Hepatol 2013; 12(1): 11–21PubMedGoogle Scholar
  9. 9.
    Teschke R, Bahre R, Genthner A, Fuchs J, Schmidt-Taenzer W, Wolff A. Suspected black cohosh hepatotoxicity—challenges and pitfalls of causality assessment. Maturitas 2009; 63(4): 302–314CrossRefPubMedGoogle Scholar
  10. 10.
    Teschke R. Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review. Menopause 2010; 17(2): 426–440CrossRefPubMedGoogle Scholar
  11. 11.
    Teschke R, Frenzel C, Schulze J, Eickhoff A. Spontaneous reports of primarily suspected herbal hepatotoxicity by Pelargonium sidoides: was causality adequately ascertained? Regul Toxicol Pharmacol 2012; 63(1): 1–9CrossRefPubMedGoogle Scholar
  12. 12.
    Teschke R, Schmidt-Taenzer W, Wolff A. USP suspected herbal hepatotoxicity: quality of causality assessment is more important than quantity of counted cases, not vice versa. Pharmocoepidemiol Drug Saf 2012; 21(3): 336–338CrossRefGoogle Scholar
  13. 13.
    Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003; 425(6954): 191–196CrossRefPubMedGoogle Scholar
  14. 14.
    Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, e SY, Lamming DW, Pentelute BL, Schuman ER, Stevens LA, Ling AJ, Armour SM, Michan S, Zhao H, Jiang Y, Sweitzer SM, Blum CA, Disch JS, Ng PY, Howitz KT, Rolo AP, Hamuro Y, Moss J, Perni RB, Ellis JL, Vlasuk GP, Sinclair DA. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 2013; 339(6124): 1216–1219PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, Criollo A, Galluzzi L, Malik SA, Vitale I, Michaud M, Madeo F, Tavernarakis N, Kroemer G. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis 2010; 1(1): e10PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Wang JB, Xiao XH, Du XX, Zou ZS, Song HB, Guo XX. Identification and early diagnosis for traditional Chinese medicineinduced liver injury based on translational toxicology. Zhongguo Zhong Yao Za Zhi 2014; 39(1): 5–9 (in Chinese)PubMedGoogle Scholar
  17. 17.
    Wang J, Zou Z, Zhao Y, Qin L, Li Q, Ma Z, Du X, Xiao X. Metabonomic biomarkers for drug-induced liver injury in rats and humans: better than alanine aminotransferase? Hepatology 2013; 58 (4): A379–A380Google Scholar
  18. 18.
    Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev 2007; 16(6): 1246–1252CrossRefPubMedGoogle Scholar
  19. 19.
    Xiaojing W, Liang Z, Chen HB, Zhao Z, Li P. Identification of Daqingye and Banlangen including crude drugs and decoction dregs from three plant species by normal light and fluorescence microscopy. Microsc Res Tech 2013; 76(8): 774–782CrossRefPubMedGoogle Scholar
  20. 20.
    Chen S, Xu J, Liu C, Zhu Y, Nelson DR, Zhou S, Li C,Wang L, Guo X, Sun Y, Luo H, Li Y, Song J, Henrissat B, Levasseur A, Qian J, Li J, Luo X, Shi L, He L, Xiang L, Xu X, Niu Y, Li Q, Han MV, Yan H, Zhang J, Chen H, Lv A, Wang Z, Liu M, Schwartz DC, Sun C. Genome sequence of the model medicinal mushroom Ganoderma lucidum. Nat Commun 2012; 3: 913PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Qiu X, Zhang J, Huang Z, Zhu D, Xu W. Profiling of phenolic constituents in Polygonum multiflorum Thunb. by combination of ultra-high-pressure liquid chromatography with linear ion trap- Orbitrap mass spectrometry. J Chromatogr A 2013; 1292: 121–131CrossRefPubMedGoogle Scholar
  22. 22.
    The State Pharmacopoeia Commission of PR China. First Div., Appendix XID. Pharmacopoeia of the People’s Republic of China. Beijing: Chemical Industry Press, 2010: Appendix 67Google Scholar
  23. 23.
    Chen X, Bian Z, Hou H, Yang F, Liu S, Tang G, Hu Q. Development and validation of a method for the determination of 159 pesticide residues in tobacco by gas chromatography-tandem mass spectrometry. J Agric Food Chem 2013; 61(24): 5746–5757CrossRefPubMedGoogle Scholar
  24. 24.
    Dalton HR, Fellows HJ, Stableforth W, Joseph M, Thurairajah PH, Warshow U, Hazeldine S, Remnarace R, Ijaz S, Hussaini SH, Bendall RP. The role of hepatitis E virus testing in drug-induced liver injury. Aliment Pharmacol Ther 2007; 26(10): 1429–1435CrossRefPubMedGoogle Scholar
  25. 25.
    Davern TJ, Chalasani N, Fontana RJ, Hayashi PH, Protiva P, Kleiner DE. Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury. Gastroenterology, 2011, 141: 1665–1672 e1–9PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Zachou K, Muratori P, Koukoulis GK, Granito A, Gatselis N, Fabbri A, Dalekos GN, Muratori L. Review article: autoimmune hepatitis — current management and challenges. Aliment Pharmacol Ther 2013; 38(8): 887–913CrossRefPubMedGoogle Scholar
  27. 27.
    Wang JB, Pu SB, Sun Y, Li ZF, Niu M, Yan XZ, Zhao YL, Wang LF, Qin XM, Ma ZJ, Zhang, YM, Li BS, Luo SQ, Gong M, Sun YQ, Zou ZS, Xiao XH. Metabolomic profiling of autoimmune hepatitis: the diagnostic utility of nuclear magnetic resonance spectroscopy. J Proteome Res 2014; 13(8): 3792–3801CrossRefGoogle Scholar
  28. 28.
    Coghlan ML, Haile J, Houston J, Murray DC, White NE, Moolhuijzen P, Bellgard MI, Bunce M. Deep sequencing of plant and animal DNA contained within traditional Chinese medicines reveals legality issues and health safety concerns. PLoS Genet 2012; 8(4): e1002657PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Gökmen MR, Cosyns JP, Arlt VM, Stiborová M, Phillips DH, Schmeiser HH, Simmonds MS, Cook HT, Vanherweghem JL, Nortier JL, Lord GM. The epidemiology, diagnosis, and management of aristolochic acid nephropathy: a narrative review. Ann Intern Med 2013; 158(6): 469–477CrossRefPubMedGoogle Scholar
  30. 30.
    Ma J, Zheng L, Deng T, Li CL, He YS, Li HJ, Li P. Stilbene glucoside inhibits the glucuronidation of emodin in rats through the down-regulation of UDP-glucuronosyltransferases 1A8: application to a drug-drug interaction study in Radix Polygoni Multiflori. J Ethnopharmacol 2013; 147(2): 335–340CrossRefPubMedGoogle Scholar
  31. 31.
    Wu X, Chen X, Huang Q, Fang D, Li G, Zhang G. Toxicity of raw and processed roots of Polygonum multiflorum. Fitoterapia 2012; 83 (3): 469–475CrossRefPubMedGoogle Scholar
  32. 32.
    Murias M, Luczak MW, Niepsuj A, Krajka-Kuzniak V, Zielinska- Przyjemska M, Jagodzinski PP, Jäger W, Szekeres T, Jodynis- Liebert J. Cytotoxic activity of 3,3',4,4',5,5'-hexahydroxystilbene against breast cancer cells is mediated by induction of p53 and downregulation of mitochondrial superoxide dismutase. Toxicol In Vitro 2008; 22(5): 1361–1370CrossRefPubMedGoogle Scholar
  33. 33.
    Ünsalan O, Kus N, Jarmelo S, Fausto R. Trans- and cis-stilbene isolated in cryogenic argon and xenon matrices. Spectrochim Acta A Mol Biomol Spectrosc 2015: 136(A): 81–94CrossRefPubMedGoogle Scholar
  34. 34.
    Lin CM, Singh SB, Chu PS, Dempcy RO, Schmidt JM, Pettit GR, Hamel E. Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study. Mol Pharmacol 1988; 34(2): 200–208PubMedGoogle Scholar
  35. 35.
    Siles R, Ackley JF, Hadimani MB, Hall JJ, Mugabe BE, Guddneppanavar R, Monk KA, Chapuis JC, Pettit GR, Chaplin DJ, Edvardsen K, Trawick ML, Garner CM, Pinney KG. Combretastatin dinitrogen-substituted stilbene analogues as tubulin- binding and vascular-disrupting agents. J Nat Prod 2008; 71(3): 313–320CrossRefPubMedGoogle Scholar
  36. 36.
    Sun J, Huang X, Wu H, Huang F. HPLC/IT-MS analysis of glycosides in radix Polygoni multiflori. Nat Prod Res Dev 2009; 21: 806–812Google Scholar
  37. 37.
    Navarro VJ, Lucena MI. Hepatotoxicity induced by herbal and dietary supplements. Semin Liver Dis 2014; 34(2): 172–193CrossRefPubMedGoogle Scholar
  38. 38.
    Verma S, Thuluvath PJ. Complementary and alternative medicine in hepatology: review of the evidence of efficacy. Clin Gastroenterol Hepatol 2007; 5(4): 408–416CrossRefPubMedGoogle Scholar
  39. 39.
    Wu X, Chen X, Huang Q, Fang D, Li G, Zhang G. Toxicity of raw and processed roots of Polygonum multiflorum. Fitoterapia 2012; 83 (3): 469–475CrossRefPubMedGoogle Scholar
  40. 40.
    la Porte C, Voduc N, Zhang G, Seguin I, Tardiff D, Singhal N, Cameron DW. Steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet 2010; 49(7): 449–454CrossRefPubMedGoogle Scholar
  41. 41.
    Crowell JA, Korytko PJ, Morrissey RL, Booth TD, Levine BS. Resveratrol-associated renal toxicity. Toxicol Sci 2004; 82(2): 614–619CrossRefPubMedGoogle Scholar
  42. 42.
    Popat R, Plesner T, Davies F, Cook G, Cook M, Elliott P, Jacobson E, Gumbleton T, Oakervee H, Cavenagh J. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol 2013; 160(5): 714–717CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Jiabo Wang
    • 1
  • Zhijie Ma
    • 1
    • 2
  • Ming Niu
    • 1
  • Yun Zhu
    • 1
    • 5
  • Qingsheng Liang
    • 3
  • Yanling Zhao
    • 1
  • Jingyuan Song
    • 4
  • Zhaofang Bai
    • 1
  • Yaming Zhang
    • 1
  • Ping Zhang
    • 5
  • Na Li
    • 1
  • Yakun Meng
    • 1
  • Qi Li
    • 1
  • Lushan Qin
    • 1
  • Guangju Teng
    • 3
  • Junling Cao
    • 6
  • Baosen Li
    • 3
  • Shilin Chen
    • 4
  • Yonggang Li
    • 7
  • Zhengsheng Zou
    • 3
  • Honghao Zhou
    • 8
  • Xiaohe Xiao
    • 5
  1. 1.China Military Institute of Chinese Medicine302 Military HospitalBeijingChina
  2. 2.Beijing Friendship HospitalCapital Medical UniversityBeijingChina
  3. 3.Diagnosis and Treatment Center for Non-infectious Diseases302 Military HospitalBeijingChina
  4. 4.Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  5. 5.Integrative Medical Center302 Military HospitalBeijingChina
  6. 6.Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina
  7. 7.Diagnosis and Treatment Center of Western and Chinese Medicine for Liver Diseases302 Military HospitalBeijingChina
  8. 8.Institute of Clinical PharmacologyCentral South UniversityChangshaChina

Personalised recommendations