Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-24T16:25:52.813Z Has data issue: false hasContentIssue false
  • English
  • Français

Analysis of herbal teas made from the leaves of comfrey (Symphytum officinale): reduction of N-oxides results in order of magnitude increases in the measurable concentration of pyrrolizidine alkaloids

Published online by Cambridge University Press:  02 January 2007

Nicholas H Oberlies ,
Nam-Cheol Kim ,
Dolores R Brine ,
Bradley J Collins ,
Robert W Handy ,
Charles M Sparacino ,
Mansukh C Wani  and
Monroe E Wall
Nicholas H Oberlies*
Affiliation:
Natural Products Laboratory, RTI International, PO Box 12194, Research Triangle Park, NC 27709, USA
Nam-Cheol Kim
Affiliation:
Natural Products Laboratory, RTI International, PO Box 12194, Research Triangle Park, NC 27709, USA Lovelace Respiratory Research Institute, Albuquerque, NM, USA
Dolores R Brine
Affiliation:
Health Sciences Unit, RTI International, Research Triangle Park, NC, USA
Bradley J Collins
Affiliation:
National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
Robert W Handy
Affiliation:
Health Sciences Unit, RTI International, Research Triangle Park, NC, USA
Charles M Sparacino
Affiliation:
Health Sciences Unit, RTI International, Research Triangle Park, NC, USA
Mansukh C Wani
Affiliation:
Natural Products Laboratory, RTI International, PO Box 12194, Research Triangle Park, NC 27709, USA
Monroe E Wall
Affiliation:
Natural Products Laboratory, RTI International, PO Box 12194, Research Triangle Park, NC 27709, USA
*
*Corresponding author: Email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objectives:

To determine the relative quantities of two hepatotoxic pyrrolizidine alkaloids, symphytine and echimidine, in teas prepared from comfrey leaves (Symphytum officinale), and to determine the potential contribution of the N-oxide forms of these alkaloids to levels of the parent alkaloids.

Design:

Comfrey leaves were purchased from three commercial sources and used to prepare tea in a manner consistent with the methods used by consumers. An extraction scheme was devised for extraction of the alkaloids, and a gas chromatographic method was developed to quantify the two major alkaloids, symphytine and echimidine. Recognising that the N-oxide derivatives of these alkaloids have also been identified in comfrey preparations, chemical reduction was applied to determine the total quantities of the alkaloids as free bases and as N-oxide derivatives.

Results:

The concentration of symphytine and echimidine varied considerably between teas prepared from leaves purchased from the different vendors of plant material. Moreover, a much higher concentration of symphytine was found in the tea when steps were included to reduce N-oxides prior to analysis. The treatment of pure symphytine with hot water did not generate the N-oxide derivative de novo.

Conclusions:

Since the pyrrolizidine alkaloids are known to be hepatotoxic, consumption of herbal teas made from comfrey leaves may be ill-advised. The concentration of pyrrolizidine alkaloids in such teas may be underestimated substantially unless the concentration of N-oxides is taken into consideration.

Keywords

ComfreyPyrrolizidineN-oxideSymphytum officinaleSymphytineEchimidine
Type
Research Article
Information
Public Health Nutrition , Volume 7 , Issue 7 , October 2004 , pp. 919 - 924
Copyright
Copyright © The Authors 2004

References

1Tyler, VE. The Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies, 3rd ed. New York: Pharmaceutical Products Press, 1992.Google Scholar
2Betz, JM, Eppley, RM, Taylor, WC, Andrzejewski, D. Determination of pyrrolizidine alkaloids in commercial comfrey products (Symphytum sp.). Journal of Pharmaceutical Sciences 1994; 83: 649–53.CrossRefGoogle ScholarPubMed
3Stickel, F, Seitz, HK. The efficacy and safety of comfrey. Public Health Nutrition 2000; 3: 501–8.CrossRefGoogle ScholarPubMed
4Bisset, NG, Wichtl, M. Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis. Stuttgart/Boca Raton, FL: Medpharm Scientific Publishers/CRC Press, 1994.Google Scholar
5American Herbal Products Association, McGuffin M. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997.Google Scholar
6Mattocks, AR, White, INH. The conversion of pyrrolizidine alkaloids to N-oxides and to dihydropyrrolizine derivatives by rat-liver microsomes in vitro. Chemico-Biological Interactions 1971; 3: 383–96.CrossRefGoogle ScholarPubMed
7Mattocks, AR. Acute hepatotoxicity and pyrrolic metabolites in rats dosed with pyrrolizidine alkaloids. Chemico-Biological Interactions 1972; 5: 227–42.CrossRefGoogle ScholarPubMed
8Mattocks, AR. Hepatotoxic effects due to pyrrolizidine alkaloid N-oxides. Xenobiotica 1971; 1: 563–5.CrossRefGoogle ScholarPubMed
9White, INH, Mattocks, AR. Some factors affecting the conversion of pyrrolizidine alkaloids to N-oxides and to pyrrolic derivatives in vitro. Xenobiotica 1971; 1: 503–5.CrossRefGoogle ScholarPubMed
10Williams, DE, Reed, RL, Kedzierski, B, Dannan, GA, Guengerich, FP, Buhler, DR. Bioactivation and detoxication of the pyrrolizidine alkaloid senecionine by cytochrome P-450 enzymes in rat liver. Drug Metabolism and Disposition 1989; 17: 387–92.Google ScholarPubMed
11Williams, DE, Reed, RL, Kedzierski, B, Ziegler, DM, Buhler, DR. The role of flavin-containing monooxygenase in the N-oxidation of the pyrrolizidine alkaloid senecionine. Drug Metabolism and Disposition 1989; 17: 380–6.Google ScholarPubMed
12Mattocks, AR, Bird, I. Pyrrolic and N-oxide metabolites formed from pyrrolizidine alkaloids by hepatic microsomes in vitro: relevance to in vivo hepatotoxicity. Chemico-Biological Interactions 1983; 43: 209–22.CrossRefGoogle ScholarPubMed
13Mattocks, AR. Chemistry and Toxicology of Pyrrolizidine Alkaloids. London/Orlando, FL: Academic Press, 1986.Google Scholar
14Molyneux, RJ, Johnson, AE, Olsen, JD, Baker, DC. Toxicity of pyrrolizidine alkaloids from riddell groundsel (Senecio riddellii) to cattle. American Journal of Veterinary Research 1991; 52: 146–51.CrossRefGoogle ScholarPubMed
15Huxtable, RJ. Human health implications of pyrrolizidine alkaloids and herbs containing them. In: Cheeke, PR, ed. Toxicants of Plant Origin. Boca Raton, FL: CRC Press, 1989; 41–86.Google Scholar
16Bach, N, Thung, SN, Schaffner, F. Comfrey herb tea-induced hepatic veno-occlusive disease. American Journal of Medicine 1989; 87: 97–9.CrossRefGoogle ScholarPubMed
17Kumana, CR, Ng, M, Lin, HJ, Ko, W, Wu, PC, Todd, D. Herbal tea induced hepatic veno-occlusive disease: quantification of toxic alkaloid exposure in adults. Gut 1985; 26: 101–4.CrossRefGoogle ScholarPubMed
18Ridker, PM, Ohkuma, S, McDermott, WV, Trey, C, Huxtable, RJ. Hepatic venocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements. Gastroenterology 1985; 88: 1050–4.CrossRefGoogle ScholarPubMed
19Weston, CF, Cooper, BT, Davies, JD, Levine, DF. Veno-occlusive disease of the liver secondary to ingestion of comfrey. British Medical Journal (Clinical Research Edition) 1987; 295: 183.CrossRefGoogle ScholarPubMed
20Yeong, ML, Swinburn, B, Kennedy, M, Nicholson, G. Hepatic veno-occlusive disease associated with comfrey ingestion. Journal of Gastroenterology and Hepatology 1990; 5: 211–4.CrossRefGoogle ScholarPubMed
21McDermott, WV, Ridker, PM. The Budd–Chiari syndrome and hepatic veno-occlusive disease. Archives of Surgery 1990; 125: 525–7.CrossRefGoogle ScholarPubMed
22Prakash, AS, Pereira, TN, Reilly, PEB, Seawright, AA. Pyrrolizidine alkaloids in human diet. Mutation Research 1999; 443: 53–67.CrossRefGoogle ScholarPubMed
23Awang, DVC, Dawson, BA, Fillion, J, Girad, M, Kindack, D. Echimidine content of commercial comfrey (Symphytum spp. – Boraginaceae). Journal of Herbs, Spices and Medicinal Plants 1993; 2: 21–34.CrossRefGoogle Scholar
24Huxtable, RJ, Luthy, J, Zweifel, U. Toxicity of comfrey–pepsin preparations. New England Journal of Medicine 1986; 315: 1095.Google ScholarPubMed
25Kim, N-C, Oberlies, NH, Brine, DR, Handy, RW, Wani, MC, Wall, ME. Isolation of symlandine from the roots of common comfrey (Symphytum officinale) using countercurrent chromatography. Journal of Natural Products 2001; 64: 251–3.CrossRefGoogle ScholarPubMed
26Couet, CE, Crews, C, Hanley, AB. Analysis, separation, and bioassay of pyrrolizidine alkaloids from comfrey (Symphytum officinale). Natural Toxins 1996; 4: 163–7.CrossRefGoogle ScholarPubMed
27Culvenor, CCJ, Edgar, JA, Frahn, JL, Smith, LW. The alkaloids of Symphytum × uplandicum (Russian comfrey). Australian Journal of Chemistry 1980; 33: 1105–13.CrossRefGoogle Scholar
28Edgar, JA, Roeder, E, Molyneux, RJ. Honey from plants containing pyrrolizidine alkaloids: a potential threat to human health. Journal of Agricultural and Food Chemistry 2002; 50: 2719–30.CrossRefGoogle Scholar
29Robbers, JE, Tyler, VE. Tylers Herbs of Choice: The Therapeutic Use of Phytomedicinals. Binghamton, NY: Haworth Herbal Press, 1999.Google Scholar
30Huizing, HJ, Gadella, TWJ, Kliphuis, E. Chemotaxonomical investigations of the Symphytum officinale polyploid complex and S. asperum (Boraginaceae): the pyrrolizidine alkaloids. Plant Systematics and Evolution 1982; 140: 279–92.CrossRefGoogle Scholar
31Gu, Z-M, Zhou, D, Lewis, NJ, Wu, J, Johnson, HA, McLaughlin, JL, et al. Quantitative evaluation of annonaceous acetogenins in monthly samples of paw paw (Asimina triloba) twigs by liquid chromatography/electrospray ionization/tandem mass spectrometry. Phytochemical Analysis 1999; 10: 32–8.3.0.CO;2-D>CrossRefGoogle Scholar
32Johnson, HA, Gordon, J, McLaughlin, JL. Monthly variations in biologic activity of Asimina triloba. In: Janick, J, ed. Progress in New Crops: Proceedings of the Third National Symposium. Alexandria, VA: ASHS Press, 1996; 609–13.Google Scholar
33Santos-Gomes, PC, Fernandes-Ferreira, M. Organ- and season-dependent variation in the essential oil composition of Salvia officinalis L. cultivated at two different sites. Journal of Agricultural and Food Chemistry 2001; 49: 2908–16.CrossRefGoogle ScholarPubMed
34Mannina, L, Patumi, M, Proietti, N, Bassi, D, Segre, AL. Geographical characterization of Italian extra virgin olive oils using high-field 1H NMR spectroscopy. Journal of Agricultural and Food Chemistry 2001; 49: 2687–96.CrossRefGoogle Scholar
35Zeng, L, Zhang, R-Y, Tong, M, Lou, Z-C. Determination of nine flavonoids and coumarins in licorice root by high performance liquid chromatography. Journal of Chromatography 1990; 512: 247–54.CrossRefGoogle Scholar
36Johnson, AE, Molyneux, RJ, Merrill, GB. Chemistry of toxic range plants. Variation in pyrrolizidine alkaloid content of Senecio, Amsinckia, and Crotalaria species. Journal of Agricultural and Food Chemistry 1985; 33: 50–5.CrossRefGoogle Scholar
37Mattocks, AR. Toxic pyrrolizidine alkaloids in comfrey. Lancet 1980; 2: 1136–7.CrossRefGoogle ScholarPubMed
38Molyneux, RJ, Johnson, AE. Extraordinary levels of production of pyrrolizidine alkaloids in Senecio riddellii. Journal of Natural Products 1984; 47: 1030–2.CrossRefGoogle ScholarPubMed
39Roitman, JN. Comfrey and liver damage. Lancet 1981; 1: 944.CrossRefGoogle ScholarPubMed
40Roeder, E. Medicinal plants in China containing pyrrolizidine alkaloids. Pharmazie 2000; 55: 711–26.Google Scholar
41Ridker, PM, McDermott, WV. Comfrey herb tea and hepatic veno-occlusive disease. Lancet 1989; 1: 657–8.CrossRefGoogle ScholarPubMed