4.2. Medical plants of the family Asteraceae containing pyrrolizidine alkaloids.
<numbers in (bold) refer to Fig. 8.>
4.2.1. Eupatorium cannabinum L.
Hemp agrimony, Thoroughwort (ger. Kunigundenkraut, Wasserdost, fr. Eupatoire chanvrine, it. Canape aquatica), is a widespread plant in Europe which preferentially grows on humid soils and brook edges. The aerial, flowering parts are used as immunostimulating agent in cases of influenza infections, as a remedy against obstipation and for decreasing the cholesterol level as well as a diuretic. In these parts of the plant the unsaturated alkaloids intermedine (4), lycopsamine (5), amabiline (17), supinine (18), rinderine (22), and echinatine (23) were detected in different concentrations [141-146]. A continued use, e.g. for the purpose of decreasing the cholesterol level, should be renounced.
4.2.2. Adenostyles alliariae (Gouan) Kern
Grey adenostyl (ger. Grauer Alpendost, fr. Adénostyle alliaire), is widespread in the countries of the Alps where it grows preferentially in the region of the timber-line. Until the beginning of this century it was used by the inhabitants of the Alps as a pectoral tea and as such was relatively important. It contains the alkaloids senecionine (40), seneciphylline (45) and spartioidine (46), the total alkaloid content being ca. 0.02% and thus relatively high [147-150]. Recently, a heavy liver disease (venoocclusive disease) in an infant caused by erroneous ingestion of grey adenostyl instead of coltsfoot was reported .
4.2.3. Emilia sonchifolia (L.) DC.
Emilia herb (ger. Emilienkraut), is a medicinal plant widespread in the south of China. It is used there in folk medicine as antipyretic, as a remedy against influenza and grippal dysentery and analgetic. Following Tyrolian physician Leonhard Hohenegg, this herb is praised as a particularly effective remedy against fever, influenza, cough, and bronchitis in lay medicine . Emilia herb contains senkirkine (52) and doronine (54) in a total concentration of up to 0.2% . Application of the amounts of this herb recommended by Hohenegg would inevitably result in intoxication.
4.2.4. Petasites hybridus (L.) PH Gaertn., B. Mey & Scherb. (syn. P. officinalis Moench)
Pestilence-wort, Butter bur, Colts food (ger. Pestwurz, Grosser Huflattich, fr. Pétasite vulgaire, it. Cavo laccio, Petastite, Tussilagine maggiore), occurs in Central Europe. Its distribution extends from Denmark up to North and West Asia. It preferentially grows on river banks and brooks. The leaves and roots of this plant and preparations thereof are applied in cases of nervous and painful spasmodic stages of different genesis in the gastro-intestinal tract, liver, gallbladder and pancreas diseases, with headache, respiratory tract disease, and for the promotion of sleep. Besides the alkaloids senecionine (40), integerrimine (41), senkirkine (52), the dried root drug contains trances of petasitenine (57), neopetasitenine (58), the nontoxic alkaloids neoplatyphylline (49), isotussilagine (68), and tussilagine (70) in a total amount of 1 to 100 mg per kilogram, the leaf drug contains less than one tenth of this amount [154-156]. According to the BGA the root-stock may be applied as therapeutic agent in the treatment of acute convulsive pain in the region of the abdomen. The daily dose administered must not contain more than 1 mg of the alkaloids or alkaloid N-oxides and the duration of application is limited to four to six weeks per year .
4.2.5. Petasites spurius (Retz) RCHB
Spurious pestilence-wort (ger. Filziger Pestwurz, fr. Pétasite bâtard, Petit Taconnet), grows on the sandy river-banks of the Elbe, Saale, Havel, Oder, and Spree. In Europe its distribution area extends from Denmark, South Sweden, South Poland to Central Russia. In the Baltic Sea countries mentioned the rhizome was or is still used internally as a cough remedy. In addition to the toxic senkirkine (52) with a concentration of ca. 0.007% also the nontoxic alkaloids farfugine (31), isotussilagine (68), isotussilaginine (69), and tussilagine (70) were detected in this plant . An internal intake cannot be recommended.
4.2.6. Senecio aureus L.
Golden ragwort, Squaw weed, Life root, Stinking Willie (ger. Gold-Kreuzkraut, fr. Seneçon d'or, it. Senecione aureono) is widely distributed in North America and Canada where it grows on humid river-bank meadows. Already the Red Indians cultivated this ragwort as medicinal plant in many ways. Today it is still used by the aborigines as a remedy against injuries, internally as diaphoretic, diuretic and emmenagogue. The Red Indian wives today ingest high doses of this drug both for acceleration of the the course of labor and abortion. In Europe, especially in Germany, it is administered in homeopathy as mother tincture and as dilutions down to D3 in the case of hemorrhage of various kinds of genesis in gynecology. The drug contains the alkaloids floridanine (53), otosenine (55) and florosenine (56) in a total concentration of 0.02% [158, 159]. The presence of senecionine could not be confirmed . According to the regulations of the BGA golden ragwort is allowed to be applied internally for therapeutic purposes in humans only in concentrations from D6 on.
4.2.7. Senecio bicolor (Wild.) Tod. ssp. cineraria (syn. S. cineraria DC., syn. Cineraria maritima L.)
Dusty miller, cineraria ragwort, silver groundsel (ger. Cineraria-Kreuzkraut, Aschenkraut, fr. Seneçon cineraire) grows in the Mediterranean areas and is cultivated in Europe as ornamental plant. Extracts of the flowering herb are administered as eye drops in the treatment of corneal clouding, cataracts and conjunctivitis especially in the southern EU countries (Portugal). In the flowering plants senecionine (40), retrorsine (42), seneciphylline (45), otosenine (55), jaconine (60), and jacobine (61) were detected in a total concentration of 0.9% [161-167]. According to the regulations of the BGA in the Federal Republic of Germany eye drops are allowed to be applied externally as a homeopathic pharmaceutical with a degree of potency of D4 .
4.2.8. Senecio doronicum L.
Doronic ragwort (ger. Gamswurz-Kreuzkraut, fr. Seneçon Doronic, it. Cardonella) grows on lime soils in the Alps. Infusions of the flower-head were used by the inhabitants of the Alps as a remedy against asthma. The flowering plants contain the alkaloids doronenine (66) and bulgarsenine (67) [168, 169]. Administration of the doronic ragwort as a remedy against asthma is regarded as obsolete.
4.2.9. Senecio jacobaea L.
Tansy ragwort, European ragwort, (ger. Jakobs-Kreuzkraut, fr. Seneçon Jacobèe, it. Jacobea) is widespread in Europe. Until the beginning of this century it was used as antispasmodic, emmenagogue and in gynecology in cases of functional amenorrhea. Tansy ragwort contains a large number of PAs. The total alkaloid content amounts to 0.2 to 0.3% of the dry weight of the flowering plants. The following alkaloids were isolated from the plant: senecivernine (39), senecionine (40), integerrimine (41), retrorsine (42), usaramine (43), 21-hydroxyintegerrimine (44), seneciphylline (45), spartioidine (46), riddelline (47), jacoline (59), jaconine (60), jacobine (61), jacozine (62), (Z)-erucifoline (63), (E)-erucifoline (64), and acetylerucifoline (65) [170-190]. In short- and long-term tests performed on mice and rats the intake of both the powdered drug and extracts caused acute toxic and carcinogenic effects [191-193]. In the Ames test ingestion of an alkaloid extract gave rise to a mutagenic effect . Of course, this medicinal plant should not be used.
4.2.10. Senecio nemorensis L. ssp. fuchsii C. Gmel. (S. nemorensis L. ssp. fuchsii Celak.), and S. nemorensis ssp. nemorensis (S. nemorensis ssp. jacquinianus (RCHB.) Celak.)
Both subspecies Fuchsii ragwort (ger. Fuchs-Kreuzkraut, fr. Seneçon de Fuchs), and Nemorensis ragwort, (ger. Hain-Kreuzkraut, fr. Seneçon de Jaquin), are closely related to each other, thus allowing formation of hybrids. The distribution area of fuchsii ragwort extends from Central Europe via the northern parts of the Balkan to Caucasia. It frequently grows in forests of the montaneous regions and moreover up to an altitude of 2000 m. Nemorensis ragwort occurs throughout the European-Siberian areas up to a maximum height of 1500 m. The two herbs are applied as hemostyptic agents both in dentistry and gynecology. Recently they have also been recommended and applied as hypoglycemic agents in cases of hypertension and diabetes. Fuchsii and nemorensis ragwort contain besides the open-chain PAs of the unsaturated retronecine and saturated platynecine type such as 7- and 9-angeloylretronecine (32, 33), 7-senecioylretronecine (34), triangularine (35), fuchsisenecionine (37), and sarracine (38) also macrocyclic 12- and 13-membered, saturated and unsaturated alkaloids. These include platyphylline (48), nemorensine (51), bulgarsenine (67), senecionine (40), retroisosenine (50), doronenine (66), and the N-oxides of these in very different concentrations [195-202]. The medicinal effect is ascribed to the nontoxic, saturated alkaloids fuchsisenecionine and bulgarsenine which represent the largest proportion of the alkaloids. In a toxicologic long-term test on rats ingestion of a commercial dried drug containing besides the nontoxic major alkaloid fuchsisenecionine in a concentration of 0.37% the toxic senecionine in a concentration of 0.007% caused a dose-dependent hepatotoxic and carcinogenic effect. This effect is attributed to senecionine . An alkaloid mixture of the same concentration displayed weak mutagenic effects [203, 204]. As hemostyptic agent only extracts of Senecio nemorensis ssp. fuchsii should be administered because in these extracts the portion of toxic alkaloids is much lower than that in S. nemorensis ssp. nemorensis. The portion of toxic alkaloids of the retronecine type such as senecionine, retroisosenine, and doronenine should therefore be less than 1 mg. Diabetics who frequently had taken ragwort tea for several years in order to support their therapy should not use such extracts because of the health risks associated with their ingestion. The BGA generally considers a medicinal application of fuchsii ragwort and nemorensis ragwort no longer justified .
4.2.11. Senecio vulgaris L.
Common ragwort, Common groundsel, Grindsel (ger. Gewöhnliches Kreuzkraut, fr. Seneçon vulgaire, it. Cardoncello), is widespread in the plains and mountains of Europe. In folk medicine it played a certain role as emmenagogue and in cases of functional amenorrhoea. Besides, it was applied similarly as Senecio jacobaea. Like the latter it contains an unusually large number of alkaloids up to a total content of 0.16% dry weight of the aerial whole drug. These alkaloids include senecionine (40), integerrimine (41), retrosine (42), usamarine (43), seneciphylline (45), spartoidine (46), riddelline (47), and the corresponding N-oxides [205-219]. But also in this case preparations of this ragwort should neither be recommended nor administered.
4.2.12. Tussilago farfara L.
Coltsfoot, Horsefoot (ger. Huflattich. fr. Pas d'âne, Tussilage, it. Farfaro) is an important medicinal plant not only in Europe and Asia but also in the USA and Canada. It either grows in the latter two countries or has been imported. For medicinal purposes flower buds, flowers, leaves, and roots are used. From time immemorial coltsfoot has been employed in cases of colds, asthma, influenza, gastro-enteritis, diarrhea, for metabolic stimulation, blood purification and externally for the treatment of wounds. Depending on its origin, the dry drug contains different amounts of senkirkine (52) ranging from 0.1 to 150 ppm, in some cases also 0.1 to 10 ppm of senecionine (40), besides the nontoxic alkaloids isotussilagine (68), isotussilaginine (69), tussilagine (70), and tussilaginine (71), usually in a total amount of <2 ppm [220-228]. Owing to the known hepatotoxicity and hepatocarcinogenicity of senkirkine and senecionine a Japanese working group performed a feeding experiment on rats for nearly two years. At nonphysiologic high dosage of dried flower buds hemangiosarcomas, hepatocellular adenomas and carcinomas could be detected .
In 1988, intoxication of an infant resulting in death was ascribed to coltsfoot . However, from the description of the case and the analysis of the tea mixture it was concluded that ingestion of coltsfoot was not the factor causing death. The tea mixture contained in addition to coltsfoot leaves also leaves and roots of pestilence-wort [230-232]. The BGA permits only leaves and tea mixtures the toxic PA content of which does not exceed 10 mg. With extracts and fresh plant-pressed juice the limiting value may be 1 mg. The period of application is confined to maximally six weeks a year .
<numbers in (bold red) refer to Fig. 8.>
Depending on the origin of the nectar collected by the bees, honey also contain PAs. In honey originating from Senecio jacobaea the alkaloids senecionine (40), seneciphylline (45), jacoline (59), jaconine (60), jacobine (61), and jacozine (62) were detected in a total concentration of 0.3 to 3.2 mg . From the honey of Senecio vernalis the alkaloids senecivernine (39), senecionine (40) and senkirkine (52) were isolated in a total concentration of ca. 0.5-1.0 mg . In honey from Echium plantagineum besides echimidine (13) as major component the alkaloids echiumine (30), uplandicine (8) as well as intermedine (4), lycopsamine (5), and the acetyl derivative (6, 7) of the latter two compounds were found in a total concentration of 0.27 to 0.95 mg . Macrocyclic PAs, mainly seneciphylline (45), could be detected in the concentration range of 30-70 mg/kg in a honey sample from the Alpine foothills region of Switzerland . Measurable concentrations of PAs must always be reckoned with in the case of large-area monocultures of PA-containing plants. In England, Scotland and Ireland honey from tansy ragwort is known and notorious for its strong aroma and bitter taste . This honey obviously also contains alkaloids. However, since honey is of minor importance as a staple food an intoxication may hardly occur.
Medicinal plants in Europe containing pyrrolizidine alkaloids was written by Prof. Dr. E. Röder and published in the journal "Pharmazie" 50 (1995), pages 83-98.