© Borgis - Postępy Fitoterapii 2/2007, s. 109-113
*Radosław J. Ekiert
Harmful constituents of herbs
Krakowskie Zakłady Zielarskie „Herbapol” w Krakowie S.A.
Prezes Zarządu: mgr inż. Alina Lekstan
Herbs are used by humans as medicines and spices for thousands years. They are used in prophylaxis and treat of many disorders. Till today, because of the availability, they form the base of medicinal systems in many countries. Despite herbs are generally considered to be safe, many of them contain harmful constituents. These compounds belong to the different chemical groups and exert different adverse effects. It is important to be conscious which herbs posses harmful potential and avoid adverse reactions.
The problem of medicines side effects becomes an essential matter after thalidomide disaster. The interest has been also focused on medicinal herbs. Many scientists have undertaken efforts to assess herbs safety and to identify hazardous substances of plant origin. Consequently the knowledge about poisonous substances is much better now. There are some elaborations that try to gather these data. We can mention among others „Adverse effects of herbal drugs” (1) and „Herbal medicines. A guide for health care professionals” (2). Health authorities (e.g. EMEA), which are very interested in the problem, issue documents concerning herbs safety too. This review tries to sum up shortly all these numerous, important informations.
The compounds comprised by herbs, which possess hazardous potential belong to many chemical groups. Among others they are anthranoids, cardiac glycosides, furanocoumarins, proteins, resins, saponins and constituents of essential oils. There is also a big, differentiated group of alkaloids. A lot of them are serious poisons, which can lead to death after ingestion even in miligram amount.
The constituents mentioned above cause many different adverse effects (Table 1). The most common are; hepatotoxicity, nephrotoxicity, mutagenicity, carcinogenicity and allergic reactions. The effects are usually dose-dependent with exclusion to hypersensitivity reactions which can be caused even by a trace amount of allergen.
Table 1. List of the most important harmful constituents occurring in herbs.
|Harmful constituents||Main Families/ Herbs||Adverse effects|
|Alkaloids||almost in all plant families, especially in Apocynaceae, Papaveraceae, Fabaceae and Ranunculaceae||miscellaneous effects, e.g. neurotoxicity, hepatotoxicity, cytotoxicity|
|Alkylphenols||Ginkgo biloba||allergen reactions|
|Amino acids||Blighia sapida, Medicago sativa||teratogenic, erythematosus syndrome|
|Anthranoids||Polygonaceae, Rhamnaceae, Rubiaceae, Scrophulariaceae and Liliaceae||mutagenecity, minerals depletion|
|Aristolochic acid||Aristolochiaceae||nephrotoxicity, genotoxicity|
|Cardiac glycosides||Scrophulariaceae, Ranunculaceae, Liliaceae, Apocynaceae||cardiotoxicity|
|Coumarin||Melilotus sp., Asperula odorata||neurotoxicity, hepatotoxicity|
|Cyanogenetic glycosides||Rosaceae||inhibiting of hemoglobin|
|Essential oils components (phenols, terpens)||Apiaceae, Asteraceae, Lamiaceae||miscellaneous actions, e.g. genotoxicity, hepatotoxicity, carcinogenicity, allergen reactions|
|Lectins||Viscum album, Phytolacca americana||haemagglutination|
|Oxalates||Polygonaceae, Oxalidaceae||oral and kidney injuries|
|Polyacetylenes||Cicuta virosa, Aethusa cynapium||neurotoxicity|
|Proteins||Ricinus communis, Viscum album||cytotoxicity, cardiotoxicity, gastrointestinal tract irritation|
|Resins||Podophyllum peltatum, Croton tiglium, Euphorbiaceae||gastrointestinal tract irritation, carcinogenicity|
|Saponins||Phytolacca americana||gastrointestinal tract irritation|
Harmful constituents and adverse effects
Almost all alkaloids exert a strong physiological effect. Many of them act in miligram doses and it is easy to overdose them. The most common alkaloid plants are: Atropa belladonna (atropine), Cephaelis ipecacuanha (emetine, cephaeline), Datura stramonium (hyoscyamine, atropine, scopolamine), Ephedra sinica (ephedrine), Hyoscyamus niger (hyoscyamine, scopolamine, atropine), Pausinystalia yohimbe (yohimbine), Rauwolfia serpentina (reserpine), Aconitum sp. (aconitine), Berberis vulgaris (berberine), Claviceps purpurea (ergot-alkaloids), Strychnos-nux vomica (strychnine) and Vinca minor containing a group of indole alkaloids (3). Benzophenanthridine alkaloids (e.g. chelidonine) comprised in prickly ash and bloodroot have exhibited cytotoxic action on animals (2). Sparteine is a cardiac depressant, lobeline cause nausea, vomiting and diarrhoea. Many others, like solanine, tomatine, solasonine, coniine, anagyrine, cytisine can exert hazardous effect too (4).
Pyrrolizidine alkaloids. A lot of herbs contain hepatotoxic unsaturated pyrrolizidine alkaloids. Some of them are used in phytotherapy; liferoot ( Senecio sp.), borage ( Borago officinalis) and comfrey ( Symphytum officinalis). A grate number of trials are performed for comfrey, they shown damage of liver in animals and humans (5, 6). At present comfrey can be only used externally on unbroken skin. Investigations with borage herb showed genotoxic, carcinogenic and hepatotoxic action. Pyrrolizidine alkaloids are also present in leaves of butterbur ( Petasites hybridus) and flowers and roots of Tussilago farfara (3).
Curare isoquinoline and indole alkaloids – tubocurarine and toxiferine C. It is worth to remember about tubocurarine, dimeric isoquinoline alkaloid, comprised in calabash curare – extract from bark, shoots and roots of same plants from Strychnos sp. and dimeric indole alkaloid – toxiferine C occuring in roots of plants in genus Chondrodendron (bamboo curare). The action of these alkaloids is based on strike skeletal muscles by inhibition of conductivity in motoric plate. It was used by South American Indian to the poisoning of arrows (7).
Ginkgo leaves contain alkylphenols; ginkgols and ginkgolic acids which are known irritants causing allergen reactions (8). Ginkgolic acids content is limited to a maximum of 5 ppm by German authorities (9).
Hypoglycin A, an amino acid from unripe Blighia sapida fruits, shown teratogenic effect in animal trials (10). Other substance – canavanine coming from Alfalfa can cause systemic lupus erythematosus syndrome.
Contained by Rubia tinctorum non laxative anthranoids posses mutagenic potential (11). It is worth to say that 1,8-anthranoids could be also dangerous. Long term use or abuse of these substances could lead to severe imbalance in homeostasis (12). The genotoxic effect is also suggested.
Beside alkylphenols there is also another harmful constituent in Ginkgo seeds and leaves, ginkgotoxin, a neurotoxin which is vitamin B6 analog. It is stated that the amounts in leaves is too small to exert an adverse effect (13).
Fruits of curly garden parsley ( Petroselinum crispum) contains apiole which is used as abotifatient (3). Apiole is also irritant and hepatotoxic, what is documented (14).
This compound could be named as the herb thalidomide. Since 1993 about 150 cases of severe nephropathy was reported. A disaster was caused by confusion, Aristolochia sp. was used instead of Stephania tetrandra because they both have the same Chinese name Fang Ji (15). Aristolochic acid, a strong carcinogen with genotoxicity potential (3,16) form hazardous DNA-adducts (17). Low levels of this compound is also found in Asarum sp. (1).
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1. De Smet P.A.G.M.: Adverse effects of herbal drugs (vol.1). Springer Verlag, Berlin 1992. 2. Newall C.A., Anderson L.A., Phillipson J.D.: Herbal Medicines. A guide for health-care professionals. The Pharmaceutical Press, London 1996. 3. EMEA/HMPC/246736/05. Public statement on "CPMP list of herbal drugs with serious risks, dated 1992”. EMEA, London 2005. 4. Henneberg M., Skrzydlewska E.: Zatrucia roślinami wyższymi i grzybami. PZWL, Warszawa 1984. 5. Ridker P.M., Ohkuma S., McDermott W.V. et al.: Hepatic venocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements. Gastroenterology 1985, 88,1050. 6. Weston C.F.M., Cooper B.T., Davies J.D. et al.: Veno-occlusive disease of the liver secondary to the ingestion of comfrey. Br. Med. J. 1987, 295, 183. 7. Kohlmünzer S.: Farmakognozja. Wydawnictwo Lekarskie PZWL, 2003. 8. Siegers C.P.: Cytotoxicity of alkylphenols from Ginkgo biloba. Phytomedicine 1999, 6, 281. 9. Blumenthal M., Busse W.R., Goldberg A. et al.: The Complete German Commission E Monographs-Therapeutic Guide to Herbal Medicines. American Botanical Council, Boston 1998. 10. De Smet P.A.G.M.: Health risks of herbal remedies. Drug Safety 1995. 13. 81. 11. Kawasaki Y., Goda Y., Yoshihira K.: The mutagenic constituents of Rubia tinctorum. Chem. Pharm. Bull. 1992, 40, 1504. 12. De Smet P.A.G.M.: Towards safer herbal medicines. The European Phytojournal, 1996. 13. Ansgar A., Klein M., Fiehe K. et al.: Occurrence of neurotoxic 4´-O-methylpyridoxine in Ginkgo biloba leaves, Ginkgo medications and Japanese Ginkgo food. Planta Med. 1996, 62, 548. 14. Tisserand R, Balacs T.: Essential oil safety. Edinburgh. Churchill Livingstone, 1995. 15. EMEA/HMPC/138381/2005. Public statement on the risk associated with the use of herbal products containing Aristolochia species. EMEA, London 2005. 16. Teuscher E., Lindequist U.: Biogene Gifte. Biologie-Chemie-Pharmakologie. Akademie-Verlag, Berlin 1988. 17. Nortier J.L., Martinez M.C., Schmeiser H.H. et al.: Urothelial carcinoma associated with the use of a Chinese herb ( Aristolochia fangchi). N. Engl. J. Med. 2000, 342, 1686. 18. EMEA/HMPC/139215/05. Public statement on the use of herbal medicinal products containing asarone. EMEA, London 2005. 19. Chandler R.F., Phillipson J.D., Anderson L.A.: Controversial laetrile. Pharm. J. 1984, 232-330. 20. EMEA/HMPC/137212/05. Public statement on the use of herbal medicinal products containing estragole. EMEA, London 2005. 21. Ljunggren B.: Severe phototoxic burn following celery ingestion. Arch .Dermatol. 1990, 126, 1334. 22. Boffa M.J., Gilmour E., Ead R.D.: Celery soup causing severe phototoxicity during PUVA therapy. Brit. J. Dermatol. 1996, 135, 330. 23. EMEA/HMPC/317913/2006. Reflection paper on the risk associated with furocoumarins contained in preparations of Angelica archangelica L. EMEA, London 2007. 24. Russmann S.: Kava hepatotoxicity. Ann Int. Med. 2001, 135, 68. 25. Geier F.P., Konstantinowicz T.: Kava treatment in patients with anxiety. Phytother. Res. 2004, 18, 297. 26. Anderson L.A., Phillipson J.D.: Mistletoe- the magic herb. Pharm. J. 1982, 229, 437. 27. EMEA/HMPC/138363/05. Public statement on the use of herbal medicinal products containing methyleugenol. EMEA, London 2005. 28. Gardner D.G.: Injury to the oral mucous membranes caused by the common houseplant, dieffenbachia. Oral Surg. Oral Med. Oral Pathol. 1994, 78, 631. 29. Lindsjo M.: Oxalate metabolism in renal stone disease with special reference to calcium metabolism and intestinal absorption. Scand. J. Urol. Nephrol. Suppl. 1989, 119, 1. 30. McGuffin M., Hobbs C., Upton R. et al.: American Herbal Products Association´s Botanical Safety Handbook. Boca Raton, CRC Press, USA 1997. 31. Kingsbury J.M.: Poisonous plants of the United States and Canada. Prentice-Hall Inc., 1964. 32. EMEA/HMPC/138386/05. Public statement on the use of herbal medicinal products containing pulegone and menthofuran. EMEA, London 2005. 33. Tyler V.E.: The Honest Herbal (3rd edn.). Howarth Press, New York 1993. 34. Baldwin C.A., Anderson L.A., Phillipson J.D.: What pharmacists should know about feverfew. Pharm. J. 1987, 239, 237. 35. Slifman N.R., Obermeyer W.R., Aloi B.K. et al.: Contamination of botanical dietary supplements by Digitalis lanata. N. Engl. J. Med. 1998, 339, 806. 36. Huang W.F., Wen K.C., Hsiao M.L.: Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J. Clin. Pharmacol. 1997, 37, 344. 37. Koh H.L., Woo S.O.: Chinese proprietary medicine in Singapore: regulatory control of toxic heavy metals and undeclared drugs. Drug Safety 2000, 23, 351. 38. Williamson E.M.: Drugs interactions between herbal and prescription medicines. Drug Safety 2003, 26, 1075. 39. Fugh-Berman A.: Herb-drug interactions. The Lancet 2000, 355, 134.