Eupatorium cannabinum / Koninginnekruid / Leverkruid

In de naam van... koninginnekruid

Een plant met blauw bloed. Het koninginnekruid, ook wel bekend onder de naam leverkruid. Geen zeldzame plant, want overdadig groeiend langs voedselrijke beekjes overal ten lande. Ook geen plant die we nog veel gebruiken, maar wel een vaste plant met een oude reputatie. Dus toch de moeite waard.

De oorsprong van de naam van deze plant moeten we in Duitsland zoeken. En dan stuiten we al gelijk op een merkwaardige vergissing. Want het koninginnekruid blijkt niets met een koningin van doen te hebben, maar meer met een keizerin. Om precies te zijn keizerin Cunegonda, de echtgenote van Hendrik de Heilige. Omdat zij een klooster stichtte werd zij na haar dood, zo omstreeks 1030, heilig verklaard. Dat kon blijkbaar niet verhinderen dat taalbarbaren Cunegonda, Kunigunde verbasterden tot 'Königin', dat wij weer braaf in koningin vertaalden. In de apothekersboeken werd het Herba Sanctae Kunigundae genoemd.

Mithridates Eupator
Toch heeft het koninginnekruid wel degelijk iets vorstelijk. Zijn wetenschappelijke naam is namelijk afgeleid van de naam van een koning Mithridates Eupator die zo'n 100 jaar voor Christus regeerde over Pontus, een koninkrijk in Klein-Azië. Hij lag regelmatig in de clinch met de Romeinen, maar had ook vele vijanden in zijn eigen rijk. En die vijanden bedienden zich veelal van allerlei giftige drankjes en poedertjes om van Eupator af te komen. Derhalve verdeelde deze vorst zijn kostbare tijd tussen het bestrijden van Romeinse legioenen en het bestuderen van kruiden. Dat die studie diepgaand genoemd mag worden, blijkt wel uit het gegeven dat hij allerlei giftige drankjes niet aan slaven voorzette, maar zelf opdronk. Denk nu niet dat deze Eupator een verlicht despoot was, die de leuze 'vrijheid, gelijkheid, broederschap' hoog in het vaandel had staan en daarom zijn slaven menslievend behandelde. Nee, op deze manier hoopte hij immuun te worden tegen allerlei giftige stoffen. En het hielp. Want op een gegeven ogenblik geraakte de koning in conflict met oa zijn zoon, waardoor onder diens leiding een grote opstand uitbrak. Eupator probeerde zichzelf dan van het leven te beroven. Wat hem niet lukte, zelfs niet met de zwaarste vergiften. Uiteindelijk vroeg hij een van zijn lijfwachten, hem dan maar uit zijn lijden te verlossen. Voor het zwaard bleek de vorst niet immuun.




Eupatorium cannabinum L., commonly known as hemp-agrimony is a robust perennial herbaceous plant of the Asteraceae family and the only species of the Eupatorium genus found in Europe occurring also throughout North Africa and Asia [1]. E. cannabinum has long been used for medicinal purposes being referred to by Greeks and Romans as well by the medieval Persian physician Aviccena, for what is also known as Eupatorium of Aviccena, and later by the Portuguese Renaissance pioneer in tropical medicine, Garcia da Orta (1563) [2]. Presently, hemp-agrimnony is used in both Chinese [3] and Indian [4] traditional medicine as well as in natural medicine in western countries [5] with very diverse therapeutic indications including influenza-like illnesses [6], hypertension [3, 4, 6] and as an anti-tumour agent [4]. E. cannabinum extracts has been previously characterized and reveal the presence of sesquiterpenes [7], pyrrolizidine alkaloids [3, 8] as well as several phenolic compounds [9, 10].

Sesquiterpenes were found to be a major fraction (43.3%) of essential oil from E. cannabinum aerial parts [11], being eupatoriopicrin the main component [7]. Eupatoriopicrin has been associated with induction DNA damage in Ehrlich ascites tumour [12] as well as with cytostatic activity and both in vitro and in vivo tumour growth inhibition properties in Lewis lung carcinoma and FIG 26 fibrosarcoma [13].

Pyrrolizidine alkaloids are generally associated with genotoxicity and tumourigenic activities [14], however the isomers intermedine and lycopsamine indentified in E. cannabinum have low genotoxic potency [15] and lycopsamine was shown to be non-tumourigenic in rats [16]. Additionally the phenolic compounds identified in this plant have been described to have anti-inflammatory [9], anti-parasitary [17], as well as anti-proliferative effects in several cell lines [18]. In particular, jaceosidin cytotoxic effects have been demonstrated in normal and cancer endometrial cells [19] and hispidulin was shown to efficiently inhibit growth of gastric cancer cells [20] and liver carcinoma cells without significant toxic effect in normal liver cells [21].

Although the effects of specific components of Eupatorium cannabinum L. extracts have been described, the cellular effects of the full extracts have not, until now, been investigated. Thus, here different concentrations of Eupatorium cannabinum L. ethanolic extract (EcEE) were evaluated on the colon cancer cell line HT29. Moreover we also analyzed its interactions with the synthetic phenolic compound bisphenol A (BPA) as well as with the chemotherapeutic agent Doxorubicin (DOX). Human exposure to BPA is considered generalized in the common population and its adverse health effects are the focus of intense investigation [22, 23]. On the other hand, DOX is a commonly used chemotherapeutic agent to which cell resistance can emerge [24, 25]. Plant constituents are a major source of bioactive compounds and several plants have been investigated aiming to identify potential synergistic effects with DOX (reviewed in [26]).

References

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2. da Orta G. Colloquies on the simples & drugs of India; translated with an introduction and index by Sir Clements Markham. London, United Kingdom: Henry Sotheran; 1913.
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4. Roeder E, Wiedenfeld H. Plants containing pyrrolizidine alkaloids used in the traditional Indian medicine-including ayurveda. Pharmazie. 2013;68:83–92. [PubMed]
5. Kozel C. Guía de medicina natural Vol II Plantas medicinales. Barcelona, Spain: Ediciones Omedin; 1982.
6. Jaric S, Popovic Z, Macukanovic-Jocic M, Djurdjevic L, Mijatovic M, Karadzic B, Mitrovic M, Pavlovic P. An ethnobotanical study on the usage of wild medicinal herbs from Kopaonik Mountain (Central Serbia) J Ethnopharmacol. 2007;111:160–175. doi: 10.1016/j.jep.2006.11.007. [PubMed] [Cross Ref]
7. Rucker G, Schenkel EP, Manns D, Mayer R, Hausen BM, Heiden K. Allergenic sesquiterpene lactones from Eupatorium cannabinum L. and Kaunia rufescens (Lund ex de Candolle) Nat Toxins. 1997;5:223–227. doi: 10.1002/(SICI)1522-7189(1997)5:6<223::AID-NT1>3.0.CO;2-R. [PubMed] [Cross Ref]
8. Boppre M, Colegate SM, Edgar JA, Fischer OW. Hepatotoxic pyrrolizidine alkaloids in pollen and drying-related implications for commercial processing of bee pollen. J Agric Food Chem. 2008;56:5662–5672. doi: 10.1021/jf800568u. [PubMed] [Cross Ref]
9. Chen JJ, Tsai YC, Hwang TL, Wang TC. Thymol, benzofuranoid, and phenylpropanoid derivatives: anti-inflammatory constituents from Eupatorium cannabinum. J Nat Prod. 2011;74:1021–1027. doi: 10.1021/np100923z. [PubMed] [Cross Ref]
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20. Yu CY, Su KY, Lee PL, Jhan JY, Tsao PH, Chan DC, Chen YL. Potential Therapeutic Role of Hispidulin in Gastric Cancer through Induction of Apoptosis via NAG-1 Signaling. Evid Based Complement Alternat Med. 2013;2013:518301. [PMC free article] [PubMed]
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33. Harun FB, Syed Sahil Jamalullail SM, Yin KB, Othman Z, Tilwari A, Balaram P. Autophagic cell death is induced by acetone and ethyl acetate extracts from Eupatorium odoratum in vitro: effects on MCF-7 and vero cell lines. ScientificWorldJournal. 2012;2012:439479. doi: 10.1100/2012/439479. [PMC free article][PubMed] [Cross Ref]
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Eupatorium cannabinum. Wasserdost (-hanf). Compositae.

Botanical name: Eupatorium cannabinum
Name: Eupatórium cannabínum L. Gemeiner Wasserdost, Wasserhanf, Hanfartiges Kunigundenkraut. Französisch: Eupatoire, à feuilles de chanvre, herbe de Sainte Cunégonde, chanvrin, origan de marais; englisch: Waterhemp, thoroughwort, hemp-agrimony, water-mandlin, sweet-mandlin; italienisch: Canapa aquatica; dänisch: Hampagtig Hjortetröst; polnisch: Sadziec, Konopnica; russisch: Poskonnik; schwedisch: Hampfloks; tschechisch: Konopáč; sadeč; ungarisch: Vizikender.
Namensursprung: Eupatorium war im Altertum der Name für den Odermennig Agrimonia eupatoria L., welcher nach dem König Mithridates Eupator von Pontus, der ihn gegen Leberleiden gebraucht haben soll, benannt worden ist; cannabinum ist eine Ableitung aus dem griechisch-lateinischen cannabis wegen der Ähnlichkeit der Laubblätter mit dem Hanf. Auf dieselbe Ähnlichkeit nehmen auch die deutschen Namen Wasserdost und Wasserhanf Bezug.
Volkstümliche Bezeichnungen: Nach der hl. Kunigunde heißt die Pflanze Kunigundenkraut. Andere Benennungen sind noch: Routlafekraut (Baden), Grundheil (Oberharz), Brand-Chrut (gegen brandige Geschwüre) (Glarus), brune Dosten (Oberharz), Blauwetterkühl (Baden).
Botanisches: Die 150 cm hohe, ausdauernde Pflanze mit aufrechtem, bis zum Blütenstand einfachen, kurzhaarigen, rauhbeblätterten Stengel besitzt handförmig geteilte Blätter mit lanzettlich zugespitzten, ungleich grob gesägten Abschnitten, kleine schmutzig-rote Blüten in einer dichten, schirmförmigen Doldentraube. Die protrandrischen Blüten werden von zahlreichen Insekten besucht. - Der Wasserhanf ist an feuchten Waldstellen, in Schluchten, an Ufern, mitunter auch an Dungstellen in Eurasien und Afrika zu finden und wächst meist gesellig. Blütezeit: Juli bis September.
Geschichtliches und Allgemeines:

Der Wasserhanf war schon den alten griechischen Ärzten ein bekanntes Mittel. Die Samen und Blätter, mit Wein genommen, dienten gegen Ruhr und Erkrankungen der Leber, ebenso gegen den Biß giftiger Schlangen. Als Salbe wurden die Blätter zur Heilung hartnäckiger Geschwüre benutzt. Die mittelalterlichen Väter der Botanik, die die Pflanze Kunigundenkraut, Wasserdost, Hirsenklee benennen, empfehlen ähnliche Verwendungsarten. So leistet der Wasserdost nach L. Fuchs (Basel 1543) gute Dienste gegen Erkrankungen der Leber und Milz, bei Vergiftungen, als Wundmittel, Emmenagogum und Diuretikum. Ferner sollte der Rauch des getrockneten Krautes alle giftigen Würmer vertreiben. H. Bock schreibt u. a., daß angeschossene, verwundete Hirsche das Kraut fressen, um sich zu heilen. Ich prüfte die Wirkung von neun verschiedenen Arten von Düngung auf die Entwicklung des ätherischen Öles in der Pflanze. Die ungedüngten Pflanzen hatten den höchsten Prozentgehalt von 0,36%. Durch die Düngung sank er herab bis auf 0,16%.

Wirkung

Leonhart Fuchs (Fuchs, New-Kreuterbuch, Basel 1543.) rühmt schon 1543 die vielseitige Heilkraft der Pflanze. Hieronymus Bock (Bock, Kreutterbuch, 1565, S. 181.) lobt sie als "sehr düglich, alle versehrung zu heylen". Er hält das Kunigundenkraut für ein die Manneskraft stärkendes Mittel.
Seine blutreinigende, zerteilende, expektorierende, emmenagoge und diuretische Kraft wird von Matthiolus (Matthiolus, New-Kreuterbuch, 1626, S. 351.) hervorgehoben, der ihm auch gute Wirkung bei verstopfter Leber und Milz, Ikterus und Hydrops, langwierigen Fiebern, äußerlich bei Wunden und Räude zuschreibt.
Ähnliche Indikationen sind auch Weinmann (Weinmann, J. W., Phytanthoza iconographia, Regensburg 1737, Bd. 2, S. 422.) bekannt.
Wie Boerhaave (Boerhaave, zit. b. v. Haller, Medicin. Lexicon, 1755, S. 618.) behauptet, heilten sich die Torfgräber, wenn sie geschwollene Füße hatten, lediglich mit Wasserdost.
Osiander (Osiander, Volksarzneymittel, S. 257.) führt die Pflanze gegen Skorbut an.
Nach Schulz (Schulz, Wirkg. u. Anwendg. d. dtsch. Arzneipfl., 1929, S. 258.) soll das Kraut diuretische und purgierende Eigenschaften haben und mit der Wurzel bei Menostase, chronischem Ekzem und Intermittens gebraucht werden.
Janson (Janson, ärztliche Sammelblätter 1937, S. 155.) gibt eine Mischung aus Wasserhanf, Ehrenpreis und Schlehenblüten als abführenden und stoffwechselanregenden Tee an.
Auch schweißtreibende, brechenerregende (Dragendorff, Die Heilpfl. d. versch. Völker u. Zeiten, S. 660.) und gallensekretionsfördernde (Kroeber, Das neuzeitliche Kräuterbuch, S. 376.) Wirkung wird ihm zugesprochen.
Schon um die Mitte des 19. Jahrhunderts wurde auf die vermutlich analoge Wirkung von Eupatorium cannabinum und Eupatorium perfoliatum hingewiesen (Aschenbrenner, Die neueren Arzneimittel und Arzneizubereitungsformen, S. 130, Erlangen 1851.).
Über die Inhaltsstoffe ist noch wenig bekannt. Nach älteren Untersuchungen (Wehmer, Die Pflanzenstoffe, S. 1215.) enthält das Kraut bitteres Eupatorin (Amorph. Alkaloid oder Glykosid?), dessen Vorhandensein von Kroeber (Vgl. 9.) allerdings bezweifelt wird, und Inulin (Fischer, H., Beitr. Biol. d. Pflanzen 1898, 8, 86.). Saponin konnte nicht nachgewiesen werden (Nach eigenen Untersuchungen.). Bei Untersuchungen über Toxingehalt wurden mittlere Mengen von ausfällbarem Eiweiß von mittlerer Giftigkeit gefunden (Vgl. 14).).

Verwendung in der Volksmedizin außerhalb des Deutschen Reiches (nach persönlichen Mitteilungen):

Polen: Die Wurzel als Diuretikum bei Nierenleiden.
Ungarn: Gegen Milz- und Leberleiden, Gelbsucht, Fieber und als Diuretikum; äußerlich gegen Krätze.
Anwendung in der Praxis auf Grund der Literatur und einer Rundfrage:

Eupatorium wirkt als Blutreinigungsmittel bei Erkrankungen der Leber, Galle und Milz und wird, in gleicher Weise wie Eupatorium perfoliatum, bei grippösen und intermittierenden Fiebern angewandt.
Recht häufig wird es als Diuretikum bei Hydrops, insbesondere bei beginnender Aszites und bei Ödemen der Füße sowie als Purgans (in größeren Dosen) verordnet. Ferner wird es bei Erkrankungen der Atmungsorgane wie Pneumonie, chronischer Bronchitis, Tussis und Schnupfen, auch Stockschnupfen, gegeben. Bei Schnupfen und Stockschnupfen läßt man mit Erfolg dil. D 3 inhalieren.
Äußerlich (das zerquetschte Kraut oder das "Teep" als Breiumschlag) leistet es gute Dienste bei Geschwülsten, Quetschungen und Exanthemen.
Angewandter Pflanzenteil:

Matthiolus empfiehlt das Kraut.
Nach v. Haller wurden hauptsächlich die Blätter, ferner die Wurzel gebraucht.
Geiger gibt das Kraut und die Wurzel, Herba et Radix Eupatorii seu Cannabis aquaticae, als früher offizinell an.
Schulz kennt die Verwendung der Blätter, des Krautes und der Wurzel. Zörnig, Hager und Thoms erwähnen das blühende Kraut.
Zur Herstellung der Präparate eignet sich das frische blühende Kraut (Sammelzeit: Juli bis August), demgemäß wird auch das "Teep" hergestellt. Die homöopathische Urtinktur nach dem HAB. hat den gleichen Ausgangsstoff (§ 3).

Dosierung:
Übliche Dosis:
4-5 g des Wurzelpulvers als Cholagogum und Purgans (Leclerc);
2 Teelöffel voll (= 2 g) zum kalten Auszug täglich.
½ Teelöffel der Frischpflanzenverreibung "Teep" drei- bis viermal täglich.
(Die "Teep"-Zubereitung ist auf 50% Pflanzensubstanz eingestellt.)
In der Homöopathie:
dil. D 1, dreimal täglich 10 Tropfen.
Maximaldosis:
Nicht festgesetzt.
Rezepte:
Bei Leber-, Milz- und Gallenstauungen und Hydrops:
Rp.:
Hb. Eupatorii cannabini conc. . . . 30 (= Wasserdostkraut)
D.s.: 2 Teelöffel voll mit 2 Glas Wasser kalt ansetzen, 8 Stunden ziehen lassen und tagsüber trinken.
(Teezubereitung: Der Extraktgehalt des im Verhältnis 1: 10 bereiteten Tees beträgt 1,6% gegenüber 2% bei kalter Zubereitung. Der Aschengehalt des Extraktes beträgt heiß 0,38% und kalt 0,46%. Geschmacklich scheint der heiß bereitete Tee allerdings etwas bitterer zu schmecken. Ein Ansatz 1:100 dürfte die Grenze dessen darstellen, was man noch trinken kann. Die Peroxydasereaktion ist negativ. 
1 Teelöffel voll wiegt 1 g. Der Tee wird auf Grund dieser Ergebnisse zweckmäßig kalt unter Verwendung von etwa 1 Teelöffel voll auf 1 Teeglas bereitet.).
Rezepturpreis ad chart. etwa -.41 RM.
Lehrbuch der Biologischen Heilmittel, 1938, was written by Dr. Med. Gerhard Madaus.



Planta Med. 1989 Apr;55(2):127-32.
Choleretic and hepatoprotective properties of Eupatorium cannabinum in the rat.
Lexa A, Fleurentin J, Lehr PR, Mortier F, Pruvost M, Pelt JM.
According to our results, the traditional therapeutic indications of Eupatorium cannabinum L., choleretic and hepatoprotective effects, have been widely demonstrated. An aqueous extract induces hypercholeresis in the rat, the site of bile formation is canalicular in origin and both bile acid-dependent and bile acid-independent flows could be stimulated; the extract possesses anti-necrotic properties against carbon tetrachloride-induced hepatotoxicity, reducing widely the plasma GPT level in pretreated rats.

Pharm Weekbl Sci. 1983 Dec 16;5(6):281-6.
Pyrrolizidine alkaloids, flavonoids and volatile compounds in the genus Eupatorium. Eupatorium cannabinum L., an ancient drug with new perspectives.
Hendriks H, Malingré TM, Elema ET.
Within the scope of a study of antitumour compounds in higher plants a survey is given concerning the presence of pyrrolizidine alkaloids, flavonoids and volatile compounds in Eupatorium species. Preliminary results of a phytochemical study of these compounds in E. cannabinum are also presented. From the results of a GC-MS analysis of an alkaloid extract from aerial parts of E. cannabinum the conclusion can be drawn, that the composition of pyrrolizidine alkaloids is more complicated than reported in literature. This is caused by the fact that different stereoisomers exist. The presence of at least two alkaloids with a molecular weight of 283 (supinine or isomers) and four alkaloids with a molecular weight of 299 (echinatine or isomers) could be shown. In subterranean plant material also other pyrrolizidine alkaloids are present. A great number of flavonoids, also as glycosides, have been shown in Eupatorium species, often in low quantities. Rutin, present in many Eupatorium species, could not be detected in subterranean parts of E. cannabinum. Relatively little attention has been paid to the analysis of volatile compounds (essential oils) of Eupatorium species. Thymol derivatives are often reported to be present in Eupatorium species. Thirty-five compounds could be detected by means of a GC-MS analysis in the essential oil of E. cannabinum about which no literature data were available.

BMC Complement Altern Med. 2014 Jul 24;14:264. doi: 10.1186/1472-6882-14-264.
Cytotoxicity of Eupatorium cannabinum L. ethanolic extract against colon cancer cells and interactions with Bisphenol A and Doxorubicin.
Ribeiro-Varandas E, Ressurreição F, Viegas W, Delgado M1.
BACKGROUND:
Eupatorium cannabinum L. has long been utilized in traditional medicine, however no information is available regarding cellular effects of full extracts. Here we assessed the effects of E. cannabinum ethanolic extract (EcEE) on the colon cancer line HT29. Potential interactions with bisphenol A (BPA) a synthetic phenolic compound to which humans are generally exposed and a commonly used chemotherapeutic agent, doxorubicin (DOX) were also evaluated.
METHODS:
HT29 cells were exposed to different concentrations (0.5 to 50 μg/ml) of EcEE alone or in combination with BPA or DOX. Cell viability was analyzed through resazurin assay. Gene transcription levels for NCL, FOS, p21, AURKA and bcl-xl were determined through qRT-PCR. Cytological analysis included evaluation of nuclear and mitotic anomalies after DAPI staining, immunodetection of histone H3 lysine 9 acetylation (H3K9ac) and assessment of DNA damage by TUNEL assay.
RESULTS:
Severe loss of HT29 cell viability was detected for 50 μg/ml EcEE immediately after 24 h exposure whereas the lower concentrations assayed (0.5, 5 and 25 μg/ml) resulted in significant viability decreases after 96 h. Exposure to 25 μg/ml EcEE for 48 h resulted in irreversible cell damage leading to a drastic decrease in cell viability after 72 h recovery in EcEE-free medium. 48 h 25 μg/ml EcEE treatment also induced alteration of colony morphology, H3K9 hyperacetylation, transcriptional up regulation of p21 and down regulation of NCL, FOS and AURKA, indicating reduced proliferation capacity. This treatment also resulted in drastic mitotic and nuclear disruption accompanied by up-regulation of bcl-xl, limited TUNEL labeling and nuclear size increase, suggestive of a non-apoptocic cell death pathway. EcEE/BPA co-exposure increased mitotic anomalies particularly for the lowest EcEE concentration, although without major effects on viability. Conversely, EcEE/DOX co-exposure decreased cell viability in relation to DOX for all EcEE concentrations, without affecting the DOX-induced cell cycle arrest.
CONCLUSIONS:
EcEE has cytotoxic activity on HT29 cancer cells leading to mitotic disruption and non-apoptotic cell death without severe induction of DNA damage. Interaction experiments showed that EcEE can increase BPA aneugenic effects and EcEE synergistic effects with DOX supporting a potential use as adjuvant in chemotherapeutic approaches.


Eupatorium perfoliatum / Boneset (is not Eupatorium cannabinum)

Botany
Boneset is a ubiquitous plant found growing in swamps, marshes, and shores from Canada to Florida and west to Texas and Nebraska. The plant is easily recognized by its long, tapering leaves that join each other around a single stout stem giving the impression of one long leaf pierced at the center by the stem. Hence its name perfolia, meaning “through the leaves.” The plant grows from July to October to a height of about 1 meter. It flowers in late summer with white blossoms that appear in small upright bunches. The entire plant is hairy and light green.

History
Boneset has been used as a charm and as a medicinal remedy for centuries by indigenous North Americans. As a charm, the root fibers were applied to hunting whistles with the belief that they would increase the whistle's ability to call deer. As an herbal remedy, American Indians used boneset as an antipyretic. 1 The early settlers used the plant to treat rheumatism, dropsy, dengue fever, malaria, pneumonia, and influenza. The name boneset was derived from the plant's use in the treatment of breakbone fever, a term describing the high fever that often accompanies influenza. 2 Boneset was official in the US Pharmacopeia from 1820 to 1900.

Chemistry
Boneset leaves and roots contain a variety of sesquiterpene lactones 3 , 4 as well as a number of sterols and triterpenes, including sitosterol and stigmasterol. 5 The flavonoids quercetin, kaempferol, and eupatorin and their glycosides also have been identified in the plant. 6 , 7 Boneset has not been shown to definitively contain alkaloids; however, 2 of 7 samples screened in 1 program tested positive. 8 A number of related species of Eupatorium have been shown to contain unsaturated pyrrolizidine alkaloids of the type that can cause serious liver damage. 9 More recently, acidic polysaccharides containing principally xylose and glucuronic acid have been elucidated. 10

Uses and Pharmacology
Based on data from early medical compendia, boneset is believed to have diuretic and laxative properties in small doses, while large doses may result in emesis and catharsis. 7 The “usual” dose of boneset was the equivalent of 2 to 4 g of plant administered as a fluid extract. When used as a household remedy, the plant has been taken as a tea ranging in concentration from 2 teaspoonfuls to 2 tablespoonfuls of crushed dried leaves and flowering tops steeped in a cup to a pint of boiling water. Boneset had been used by physicians to treat fever, but its use was supplanted by safer and more effective antipyretics. It is not known which components of boneset reduce fever or how effective the plant is as an antipyretic.

An ethanolic extract of the aboveground parts of the plant was found inactive in a carrageenan-induced rat paw model of inflammation. 11 The isolated polysaccharides and an extract of E. perfoliatum combined with other herbs have been shown to stimulate phagocytic activity in vitro by a carbon particle clearance technique. 12 , 13

Animal data
Research reveals no animal data regarding the use of boneset.

Clinical data
Compared with aspirin, a small double-blind clinical trial of a homeopathic preparation of boneset (N = 53) found the herbal treatment as effective in reducing symptoms of the common cold. 14 The ethanol extract of boneset leaves was shown to have modest antibacterial and cytotoxic activity; however, no fractionation to identify the constituents responsible for the activity was reported. 15

Dosage
There is no recent clinical evidence to guide dosage of boneset. Traditional use was at a dose of 2 g of leaves and flowers. Internal use should be tempered by the occurrence of hepatotoxic pyrrolizidine alkaloids in this plant.

Pregnancy/Lactation
Documented adverse effects, including cytotoxic constituents. 16 Avoid use.

Interactions
None well documented.

Adverse Reactions
Although few reports of adverse effects have been reported with the use of boneset, the FDA has classified this plant as an “Herb of Undefined Safety.”

Toxicology
The ingestion of large amounts of teas or extracts may result in severe diarrhea. The identification of pyrrolizidine alkaloids in related Eupatorium species is cause for concern until detailed phytochemical investigations are carried out on boneset. This class of alkaloids is known to cause hepatic impairment after long-term ingestion. While direct evidence for a hepatotoxic effect from boneset does not exist, there is sufficient evidence to indicate that any plant containing unsaturated pyrrolizidine alkaloids should not be ingested.

Bibliography
1. Erichsen-Brown C. Medicinal and Other Uses of North American Plants: A Historical Survey with Special Reference to the Eastern Indian Tribes . NY: Dover Press; 1989:262-264.
2. Bolyard JL. Medicinal Plants and Home Remedies of Appalachia . Springfield, IL: Thomas; 1981:59-60.
3. Bohlmann F, Mahanta PK, Suwita A, et al. Neue sesquiterpenelactone und andere inhaltstoffe aus vertretern der Eupatorium -gruppe. Phytochemistry . 1977;16:1973-1981.
4. Herz W, Kalyanaraman PS, Ramakrishnan G. Sesquiterpene lactones of Eupatorium perfoliatum . J Org Chem . 1977;42:2264-2271.
5. DomInguez XA, Gonzalez Quintanilla JA, Rojas P. Sterols and triterpenes from Eupatorium perfoliatum . Phytochemistry . 1974;13:673-674.
6. Wagner H, Iyengar MA, Hörhammer L. Flavonol-3-glucosides in eight Eupatorium species. Phytochemistry . 1972;11:1504-1505.
7. Herz W, Gibaja S, Bhat SV, Srinivasan A. Dihydroflavonols and other flavonoids of Eupatorium species. Phytochemistry . 1972;11:2859-2863.
8. Raffauf RF. Plant Alkaloids: A Guide to Their Discovery and Distribution . NY: Food Products Press; 1996:49-57.
9. Locock RA, Beal JL, Doskotch RW. Alkaloid constituents of Eupatorium serotinum . Lloydia . 1966;29:201-205.
10. Vollmar A, Schafer W, Wagner H. Immunologically active polysaccharides of Eupatorium cannabinum and Eupatorium perfoliatum . Phytochemistry . 1986;25:377-381.
11. Benoit PS, Fong HH, Svoboda GH, Farnsworth NR. Biological and phytochemical evaluation of plants. XIV. Antiinflammatory evaluation of 163 species of plants. Lloydia . 1976;39:160-171.
12. Wagner H, Proksch A, Riess-Maurer I, et al. Immunostimulating action of polysaccharides (heteroglycans) from higher plants [in German]. Arzneimittelforschung . 1985;35:1069-1075.
13. Wagner H, Jurcic K. Immunologic studies of plant combination preparations. In-vitro and in- vivo studies on the stimulation of phagocytosis [in German]. Arzneimittelforschung . 1991;41:1072-1076.
14. Gassinger CA, Wunstel G, Netter P. A controlled clinical trial for testing the efficacy of the homeopathic drug Eupatorium perfoliatum D2 in the treatment of common cold [in German]. Arzneimittelforschung . 1981;31:732-736.
15. Habtemariam S, Macpherson AM. Cytotoxicity and antibacterial activity of ethanol extract from leaves of a herbal drug, boneset ( Eupatorium perfoliatum ). Phytother Res . 2000;14:575-577.
16. Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals . London: Pharmaceutical Press; 1996.
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