Mutterkraut

Zusammenfassung

Anfang der Siebzigerjahre des letzten Jahrhunderts wurde in einer englischen Zeitung über die heilende Wirkung von Mutterkraut (Tanacetum parthenium, Asteraceae) bei Migräne berichtet. In der Folge wurden die Chemie und Pharmakologie dieser traditionellen Heilpflanze intensiv beforscht und klinische Studien durchgeführt. Als Wirksubstanz steht Parthenolid im Fokus, ein Sesquiterpenlacton mit hoher biologischer Aktivität, die sich durch eine exocyclische Doppelbindung im Lactonring erklären lässt. Weitere 34 Sesquiterpenlactone wurden in der Droge nachgewiesen, außerdem verschiedene lipophile Flavonoide sowie ein ätherisches Öl mit ca. 50 Komponenten und (S)-(-)-Campher, trans-Chrysanthenylacetat und Camphen als Hauptkomponenten. Die Ergebnisse der klinischen Studien waren sehr unterschiedlich und konnten die Wirksamkeit als Migräneprophylaktikum nicht überzeugend bestätigen, sodass Mutterkraut den Sprung zum Arzneimittel noch nicht endgültig geschafft hat, obwohl die pharmakologische Datenlage vielversprechend ist. Mutterkrautextrakte und/oder Parthenolid greifen in verschiedene Vorgänge des Entzündungsgeschehens ein, wodurch sich die Wirkung bei Migräne und Arthritis erklären lässt. In Bezug auf die Wirkung von Mutterkraut wird auch das Zusammenspiel verschiedener Inhaltsstoffe der Droge diskutiert sowie die möglichen toxikologischen Eigenschaften, Nebenwirkungen und Interaktionen.

Summary

In the early 1970s an English newspaper reported on the successful use of feverfew (Tanacetum parthenium, Asteraceae) for migraine, initiating intensive chemical and pharmacological studies of this traditional herb. Attention was focused on parthenolid, a sesquiterpene lactone with high biological activity. It is held responsible for the anti-migraine effect of feverfew. 34 further sesquiterpene lactones were identified in the herb as well as several lipophilic flavonoids and an essential oil with about 50 components, (S)-(-)-camphor, trans-chrysanthenyl acetate and camphene being the major components. The clinical trials for treatment of migraine were not really convincing which prevented feverfew from achieving the status of an herbal medicinal product. But promising pharmacological data do exist: Extracts of feverfew and/or parthenolid were shown to interfere in several inflammatory processes which may explain their effects on migraine and arthritis. Nevertheless toxicology, side effects and interactions of the herb must be discussed.

Schlüsselwörter

Mutterkraut - Tanacetum parthenium (L.) Schultz Bip. - Asteraceae - Parthenolid - Migräne - Pharmakologie - klinische Studien

Key words

Feverfew - Tanacetum parthenium (L.) Schultz Bip. - Asteraceae - parthenolid - migraine - pharmacology - clinical trials

Literatur

• 1 Berry MI. Feverfew faces the future.  Pharm J. 1984;  232 611-614
• 2 Groenewegen WA, Knight DW, Heptinstall S. Progress in the medicinal chemistry of the herb feverfew.  In: Ellis GP, Luscombe DK (ed.): Progress in Medicinal Chemistry  Amsterdam: Elsevier. 1992;  29 217-238
• 3 Knight DW. Feverfew: chemistry and biological activity.  Nat Prod Rep. 1995;  12 271-276
• 4 Heptinstall S, Awang DVC. Ferverfew: A Review of its history, its biological and medical properties, and the status of commercial preparations of the herb. In: Lawson LD, Bauer R (ed.): Phytomedicines of Europe. ACS Symposiums Series 691, Washington DC: American Chemical Society 1998: 158-175
• 5 Awang DVC, Leung AY. Feverfew (Tanacetum parthenium). In: Coates PM (ed.): Encyclopedia of Dietary Supplements. New York: Marcel Dekker 2006: 211-217
• 6 Pharmacopée Francaise. Xième edition Paris 2000
• 7 British Herbal Pharmacopoeia; 4th edition;. Scientific Committee of the Herbal Medicine Association 1996
• 8 Martindale's Pharmacopoeia; Reynolds, J.E.F., 30th edition;. Royal Pharmaceutical Society: London 1996
• 9 Mutterkraut - Tanaceti herba. Europäisches Arzneibuch - Pharmacopoeia Europaea 2005
• 10 Wichtl M. Teedrogen und Phytopharmaka. 4. Aufl. Stuttgart: Wiss. Verlagsgesellschaft 2002: 668-669
• 11 Tanaceti Parthenii Herba - Fewerfew. In: European Scientific Cooperative on Phytotherapy (ed.) ESCOP Monographs, 2. edition. Stuttgart; London: Thieme 2003: 492-498
• 12 Awang DVC. Feverfew effective in migraine prevention.  HerbalGram. 1998;  42 18
• 13 Herout V, Soucek M, Sorm F. Parthenolide, another sesquiterpenic lactone with a tenmembered ring. Chem & Ind 1959: 1069-1070
• 14 Govindachari TR, Joshi BS, Kamat VN. Structure of parthenolid.  Tetrahedron. 1965;  21 1509-1519
• 15 Bawdekar AS, Kelkar GR, Bhattacharyya SC. Terpenoids. LXXXIX. Absolute configuration of parthenolide. Tetrahedron Lett 1966: 1225-1227
• 16 Quick A, Rogers D. Crystal and molecular structure of parthenolide [4,5-epoxygermacra-1(10),11(13)-dien-12,6-olactone].  J Chem Soc, Perkin Trans. 2;  1976 465-469
• 17 Bohlmann F, Zdero C. Naturally occurring terpene derivatives; Part 454: Sesquiterpene lactones and other constituents from Tanacetum parthenium.  Phytochemistry. 1982;  21 2543-2549
• 18 Romo J, RomodeVivar A, Trevino R. et al. . Constituents of Artemisia and Chrysanthemum species. Structures of chrysartemins A and B.  Phytochemistry. 1970;  9 1615-1621
• 19 Todorova MN, Evstatieva LN. Comparative study of Tanacetum species growing in Bulgaria.  Zeitschr Naturforsch C: J Biosci. 2001;  56 506-512
• 20 Williams CA, Hoult JRS, Harborne JB. A biologically active lipophilic flavonol from Tanacetum parthenium.  Phytochemistry. 1995;  38 267-270
• 21 Williams CA, Harborne JB, Geiger H. et al. . The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties [Erratum to document cited in CA131:142071].  Phytochemistry. 1999;  52 1181-1182
• 22 Williams CA, Harborne JB, Eagles J. Variations in lipophilic and polar flavonoids in the genus Tanacetum.  Phytochemistry. 1999;  52 1301-1306
• 23 Long C, Sauleau P, David B. et al. . Bioactive flavonoids of Tanacetum parthenium revisited.  Phytochemistry. 2003;  64 567-569
• 24 Ravid U, Putievsky E, Katzir I. Determination of the enantiomeric composition of (1R)(+)- and (1S)(-)-camphor in essential oils of some Lamiaceae and Compositae herbs.  Flav Fragr J. 1993;  8 225-228
• 25 Pooter HL De, Vermeesch J, Schamp NM. The essential oils of Tanacetum vulgare L. and Tanacetum parthenium (L.) Schultz-Bip.  J Essent Oil Res. 1989;  1 9-13
• 26 Hendriks H, Bos R, Woerdenbag HJ. The essential oil of Tanacetum parthenium (L.) Schultz-Bip.  Flav Fragr J. 1996;  11 367-371
• 27 Lawrence BM. Progress in essential oils: Feverfew oil and extract.  Perfum Flavor. 1999;  24 54-56
• 28 Johnson ES. Feverfew, a Traditional Herbal Remedy for Migraine and Arthritis. London: Sheldon Press 1984
• 29 Johnson ES. Patients who chew chrysanthemum leaves.  MIMS Magazine. 1983;  32
• 30 Johnson ES, Kadam NP, Hylands DM. et al. . Efficacy of feverfew as prophylactic treatment of migraine.  Br Med J. 1985;  291 569-573
• 31 Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention.  Lancet. 1988;  2 189-192
• 32 Pittler MH, Ernst E. Feverfew for preventing migraine. Update of: Cochrane Database Syst Rev. 2000;(3):CD002286. Cochrane database of systematic reviews 2004
• 33 Pfaffenrath V, Diener HC, Fischer M. et al. . The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis - a double-blind, multicentre, randomized placebo-controlled dose-response study.  Cephalalgia. 2002;  22 523-532
• 34 Diener HC, Pfaffenrath V, Schnitker J. et al. . Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention - a randomized, double-blind, multicentre, placebo-controlled study.  Cephalalgia. 2005;  25 1031-1041
• 35 Cady RK, Schreiber CP, Beach ME. et al. . Gelstat Migraine (sublingually administered feverfew and ginger compound) for acute treatment of migraine when administered during the mild pain phase.  Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2005;  11 65-69
• 36 Shrivastava R, Pechadre JC, John GW. Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis. A prospective, open-label study.  Clin Drug Investig. 2006;  26 287-296
• 37 Pattrick M, Heptinstall S, Doherty M. Feverfew in rheumatoid arthritis: a double blind, placebo controlled study.  Ann Rheumatic Diseases. 1989;  48 547-549
• 38 Collier HOJ, Butt NM, McDonald-Gibson WJ. et al. . Extract of feverfew inhibits prostaglandin biosynthesis.  Lancet. 1980;  2 922-923
• 39 Makheja AM, Bailey JM. The active principle in feverfew.  Lancet. 1981;  2 1054
• 40 Makheja AN, Bailey JM. A platelet phospholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium).  Prostaglandins Leukot Med. 1982;  8 653-660
• 41 Thakkar JK, Sperelaki N, Pang D. et al. . Characterization of phospholipase A2 activity in rat aorta smooth muscle cells.  Biochim Biophys Acta. 1983;  750 134-140
• 42 Lösche W, Groenewegen WA, Krause S. et al. . Effects of an extract of feverfew (Tanacetum parthenium) on arachidonic acid metabolism in human blood platelets.  Biomed Biochim Acta. 1988;  47 241-243
• 43 Keery RJ, Lumley P. Br J Pharmacol.  1986;  89 834P
• 44 Capasso F. The effect of an aqueous extract of Tanacetum parthenium L. on arachidonic acid metabolism by rat peritoneal leucocytes.  J Pharm Pharmacol. 1986;  38 71-72
• 45 Pugh WJ, Sambo K. Prostaglandin synthetase inhibitors in feverfew.  J Pharm Pharmacol. 1988;  40 743-745
• 46 Heptinstall S, White A, Williamson L. et al. . Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes.  Lancet. 1985;  1 1071-1074
• 47 Lösche W, Michel E, Heptinstall S. et al. . Inhibition of the behaviour of human polynuclear leukocytes by an extract of Chrysanthemum parthenium.  Planta Med. 1988;  54 381-384
• 48 Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in vitro.  J Pharm Pharmacol. 1990;  42 553-557
• 49 Hayes NA, Foreman JC. The activity of compounds extracted from feverfew on histamine release from rat mast cells.  J Pharm Pharmacol. 1987;  39 466-470
• 50 Williamson LM, Harvey DM, Sheppard KJ. et al. . Effect of feverfew on phagocytosis and killing of Candida guilliermondii by neutrophils.  Inflammation. 1988;  12 11-16
• 51 Johnson ES, Hylands PJ, Hylands DM. Eur Pat, EP 98 401 (G.B. Pat 1982; 82/14572).  CA. 1984;  100 197778-11977786
• 52 Barsby RW, Salan U, Knight DW. et al. . Feverfew extracts and parthenolide irreversibly inhibit vascular responses of the rabbit aorta.  J Pharm Pharmacol. 1992;  44 737-740
• 53 Hay AJ, Hamburger M, Hostettmann K. et al. . Toxic inhibition of smooth muscle contractility by plant-derived sesquiterpenes caused by their chemically reactive alpha-methylene butyrolactone functions.  Br J Pharmacol. 1994;  112 9-12
• 54 Barsby RW, Knight DW, McFadzean I. A chloroform extract of the herb feverfew blocks voltage-dependent potassium currents recorded from single smooth muscle cells.  J Pharm Pharmacol. 1993;  45 641-645
• 55 Voyno-Yasenetskaya TA, Lösche W, Groenewegen WA. et al. . Effects of an extract of feverfew on endothelial cell integrity and on cAMP in rabbit perfused aorta.  J Pharm Pharmacol. 1988;  40 501-502
• 56 Lösche W, Mazurov AV, Heptinstall S. et al. . An extract of feverfew inhibits interactions of human platelets with collagen substrates.  Thromb Res. 1987;  48 511-518
• 57 Jain NK, Kulkarni SK. Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats.  J Ethnopharmacol. 1999;  68 251-259
• 58 Groenewegen WA, Knight DW, Heptinstall S. Compounds extracted from feverfew that have antisecretory activity contain an alpha-methylene butyrolactone unit.  J Pharm Pharmacol. 1986;  38 709-712
• 59 Heptinstall S, Groenewegen WA, Knight DW. et al. .In: Current Problems in Neurology 4. Advances in Headache Research, Proceedings of the 6th International Migraine Symposium 1987. Clifford Rose, F. John Libbey and Co. Ltd.: London 129-134
• 60 Hewlett MJ, Begley MJ, Groenewegen WA. et al. . Sesquiterpene lactones from feverfew, Tanacetum parthenium: isolation, structural revision, activity against human blood platelet function and implications for migraine therapy.  J Chem Soc, Perkin Trans. 1;  1996 1979-1986
• 61 Marles JR, Pazos-Sanou L, Compadre CM. et al. . Sesquiterpene lactones revisited: Recent development in the assessment of biological activities and structure relationships.  Recent Adv Phytochem. 1995;  29 333-356
• 62 Marles RJ, Kaminski J, Arnason JT. et al. . A bioassay for inhibition of serotonin release from bovine platelets.  J Nat Prod. 1992;  55 1044-1056
• 63 Heptinstall S, Awang DVC, Dawson BA. et al. . Parthenolide content and bioactivity of feverfew (Tanacetum parthenium (L.) Schultz-Bip.). Estimation of commercial and authenticated feverfew products.  J Pharm Pharmacol. 1992;  44 391-395
• 64 Mittra S, Datta A, Singh SK. et al. . 5-Hydroxytryptamine-inhibiting property of feverfew: role of parthenolide content.  Acta Pharmacol Sinica. 2000;  21 1106-1114
• 65 Bejar E. Parthenolide inhibits the contractile responses of rat stomach fundus to fenfluramine and dextroamphetamine but not serotonin.  J Ethnopharmacol. 1996;  50 1-12
• 66 Hwang D, Fischer NH, Jang BC. et al. . Inhibition of the expression of inducible cyclooxygenase and proinflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases.  Biochem Biophys Res Comm. 1996;  226 810-818
• 67 Bork PM, Lienhard-Schmitz ML, Kuhnt M. et al. . Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB.  FEBS Lett. 2007;  402 85-90
• 68 Smolinski AT, Pestka JJ. Comparative effects of the herbal constituent parthenolide (feverfew) on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver.  J Inflamm (Lond). 2005;  2 6
• 69 Reuter U, Chiarugi A, Bolay H. et al. . Nuclear factor-kappaB as a molecular target for migraine therapy.  Ann Neurol. 2002;  54 507-516
• 70 Tassorelli C, Greco R, Morazzoni P. et al. . Parthenolide is the component of Tanacetum parthenium that inhibits nitroglycerin-induced Fos activation: studies in an animal model of migraine.  Cephalalgia. 2005;  25 612-621
• 71 Khan SI, Abourashed EA, Khan IA. et al. . Transport of parthenolide across human intestinal cells (Caco-2).  Planta Med. 2003;  69 1009-1012
• 72 Heptinstall S, Groenewegen WA, Spangenberg P. et al. . Extracts of feverfew may inhibit platelet behaviour via neutralization of sulfhydryl groups.  J Pharm Pharmacol. 1987;  39 459-465
• 73 Heptinstall S, Groenewegen WA, Spangenberg P. et al. . Inhibition of platelet behaviour by feverfew: a mechanism of action involving sulfhydryl group.  Folia Haematologica. 1988;  115 447-449
• 74 Weerdt CJ De, Bootsma HP, Hendriks H. Herbal medicines in migraine prevention.  Phytomedicine. 1996;  3 225-230
• 75 Barsby RW, Salan U, Knight DW. et al. . Feverfew and vascular smooth muscle: extracts from fresh and dried plants show opposing pharmacological profiles, dependent upon sesquiterpene lactone content.  Planta Med. 1993;  59 20-25
• 76 Sumner H, Salan U, Knight DW, Hoult JR. Inhibition of 5-lipoxygenase and cyclo-oxygenase in leukocytes by feverfew. Involvement of sesquiterpene lactones and other components.  Biochem Pharmacol. 1992;  43 2313-2320
• 77 Brown AM, Edwards CM, Davey MR. et al. . Pharmacological activity of feverfew (Tanacetum parthenium (L.) Schultz-Bip.): assessment by inhibition of human polymorphonuclear leukocyte chemiluminescence in vitro.  J Pharm Pharmacol. 2007;  49 558-561
• 78 Hoult JR, Pang L-H, Bland-Ward PA. et al. . Inhibition of leukocyte 5-lipoxygenase and cyclo-oxygenase but not constitutive nitric oxide synthase by tanetin, a novel flavonol derived from feverfew, Tanacetum parthenium.  Pharm Sci. 1995;  1 71-74
• 79 Hausen BM. Occupational contact allergy to feverfew Tanacetum parthenium (L.) Schultz-Bip.; Asteraceae. Dermatosen in Beruf und Umwelt.  Occupation and Environment. 1981;  29 18-21
• 80 Paulsen E, Andersen KE, Hausen BM. Sensitization and cross-reaction patterns in Danish Composite-allergic patients.  Contact Dermatitis. 2001;  45 197-204
• 81 Hausen BM, Osmundsen PE. Contact allergy to parthenolide in Tanacetum parthenium (L.) Schulz-Bip. (Feverfew, Asteraceae) and cross-reactions to related sesquiterpene lactone containing Compositae species.  Acta Dermato-Venereologica. 1983;  63 308-314
• 82 Christensen LP, Jakobsen HB, Paulsen E. et al. . Airborne Compositae dermatitis: Monoterpenes and no parthenolide are released from flowering Tanacetum parthenium (feverfew) plants.  Archiv Dermatol Res. 1999;  291 425-431
• 83 Paulsen E, Christensen LP, Andersen KE. Do monoterpenes released from feverfew (Tanacetum parthenium) plants cause airborne Compositae dermatitis?.  Contact Dermatitis. 2002;  47 14-18
• 84 Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction.  Rapid Commun Mass Spectr. 2004;  18 2273-2281