13 MATERIA MEDICA

Boneset in Dyspesia and Febrile Infections Francis Brinker, ND

Distribution and description Canada, and differentiation can be difficult (Locock Boneset ( perfoliatum L.) is a widespread 1990). Former Latin synonyms for this species are E. native in the eastern and central United States and connatum, E. glandulosum, and E. viginicum Canada. It ranges from Nova Scotia to Florida and west (Woerdenbag 1993). The species name “perfoliatum” to Texas and North Dakato. It can be found growing in describes how the attach to each other around low damp soil over large areas and in thickets. Due to its the stem, making the stem appear to pierce through association with swampy places, its early use by Native them (Mundy 1905). Common names used included Americans for malaria seemed most appropriate (Foster thoroughwort, thorough-stem, and crosswort & Duke 1990, Locock 1990). (Anon. 1918). “Thorough” in this context likewise The opposite, lanceolate and perfoliate leaves are means “passing through”, another term describing the long, wrinkled, and hairy underneath, turning dull gray stem and the leaves, as crosswort likely also addresses Francis Brinker has after the flowers appear. A hardy perennial that grows this conjunction. taught botanical from 1-4 feet high, it has a large, flat, terminal cluster of Of the common names applied to this plant, medicine at both National College of greyish white to pale purplish flowers that appears from boneset is now more typically familiar to modern Naturopathic Medicine July to August and persist until frost, typically in herbalists. This name refers to its use for febrile and Southwest College October. The leaves turn a dull gray after the flowers conditions with characteristic aching of the bones. of Naturopathic appear. The recently picked leaves and flowering tops are Indian sage was another name used by European settlers Medicine and currently the parts normally used for medicine. An infusion of who used it to induce a sweat for in fevers. The plant has serves as an Assistant 2-4 grams of the recently harvested parts was the popular also been known as ague weed. Wooster Beach, the father Clinical Professor in form to use both by indigenous peoples and in Anglo of Eclecticism, called it “vegetable antimony,” using it as the College of folk medicine as a diaphoretic, analgesic, emetic, and/or a replacement for the toxic mineral drug antimony Medicine at the laxative. In addition, the tincture, fluid extract, and tartrate, or tartar emetic (Locock 1990, Mundy 1905, University of Arizona. Specific Medicine were employed by Eclectics and other Powers 1928). Dr. Brinker has written doctors for fevers in endemic and epidemic infections Several Composite family were also called numerous articles and (Foster & Duke 1990, Hall 1974, Locock 1990, Mundy boneset and in the early 20th century were occasionally books on medicinal 1905, Powers 1928). misrepresented as the preferred species. Though their herbs, including Complex Herbs – flowers bore a general resemblance, the leaves were Complete Medicines, completely unalike. One was Eupatorium ageratoides, The Eclectic Eupatorium perfoliatum is a member of the also known as white snake-root, an herb that was Dispensatory of (Composite) family of plants. The genus takes its name diuretic, diaphoretic and antispasmodic. Another was Botanical Therapeutics, from the ancient king Mithridates Eupator of Pontus Gnaphalium polycephalum, called sweet-scented life- Herb Contraindications who is believed to have used one of these species in his everlasting, Indian posy, or old-field balsam, due to its and Drug Interactions, famous poisoning-prevention formula. As many as very fragrant aroma. Its infusion or decoction was used and The Toxicology of 26 different species grow in the American northeast near as a cold and flu remedy (Anon. 1918). Botanical Medicine.

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Ague weed employed by Native Americans Schopf, M.D., noted in his Latin text its use by Indians Eupatorium perfoliatum is one of the first botanical for fever and cough. Benjamin Smith Barton, M.D., remedies to be introduced to the American colonists by professor of natural history and botany at the University the Indians. In this instance it was employed to treat the of Pennsylvania, indicated in 1798 that thoroughwort common malarial fever known as the ague. This remedy decoction was emetic and used by Indians for was used by the Indians for malaria so often that it intermittent fevers. James Thatcher, M.D., in 1810 became known as “ague weed” (Hall 1974, Mundy declared its sudorific, emetic, and purgative powers for 1905, Powers 1928). The leaves or the whole plant were fevers, taken as a decoction or as powdered leaves, infused, and the tea consumed as a treatment for ague though he believed the flowers were the most active. By and other fevers by a number of Indian tribes including 1814 the botanist Frederick Pursh found the whole plant the Cherokee, Delaware, Iroquois, Menominee, exceedingly bitter but effective in treating influenza and Mohegan, Nanticoke, Seminole, and Shinnecock other fevers (Anon. 1918). (Moerman 1998). In 1817 Jacob Bigelow, M.D., professor of materia In other debilitating circumstances such as colds, medica and botany at Harvard University, reported its the infusion was employed as a bitter tonic and a means usefulness for many cutaneous affections and for to increase sweating by the Cherokee, Mohegan, and intermittent and other fevers when taken as a dried herb Shinnecock, or simply taken as a tonic by the or its decoction. In 1818 William P.C. Barton, M.D., Rappahannock. The Indians, moreover, considered the professor of botany at the University of Pennsylvania, ...the infusion leaves and tops a powerful remedy for use internally or declared that “few plants of our country are more and decoction of locally in a variety of other conditions. The Meskwaki deserving of the attention of physicians than this.” He (Fox) drank as infusion of leaves and blossoms to expel found it an inestimable medicine is all cases of low boneset were long worms. It was a well-known emetic among the typhus with hot, dry skin when given every half hour to popular with Cherokee, Koasati, and Seminole and taken also a ensure diaphoresis and avoid emesis. The next year the American laxative by the Cherokee and Iroquois. Iroquois applied professor of clinical practice at the University of physicians for a poultice of the smashed plant for headaches. The Pennsylvania, N. Chapman, M.D., indicated boneset Chippewa (Ojibwa) made a poultice of the boiled tops was the most valuable of diaphoretics. The entire plant, colds and flu... for rheumatism, and applied the chewed plant locally for but especially the flowers, hardly ever failed in this regard rattlesnake bites (Moerman 1998). when used as a strong infusion. Used in early stages of The root was also utilized and preferred by some catarrhal affections, he reported how 30 years prior its tribes. The Meskwaki made a poultice of the root for efficacy in treating a type of influenza called “break bone snakebites. The roots or other parts of the plant were fever” led to its being given the enduring name boneset. used by the Iroquois and other tribes for lung, pleuritic, When given hot as an infusion or decoction, it is stomach, urinary tract, and menstrual pains. Iroquois diaphoretic, emetic, and diuretic, but as a cold decoction also decocted the root to help stop the liquor habit. its tonic effects predominate (Anon. 1918). It was Chippewa used the root to correct irregular included under the name thoroughwort in the primary menstruation (Moerman 1998). list of materia medica in the first edition of the Pharmacopoeia of the United States where it was also Early history of its commendation in designated as an official infusion (USP 1820). Euro-American medical literature For many decades white settlers also relied on this After being introduced to settlers by the natives, the plant as a popular remedy for malaria. Peruvian bark was infusion and decoction of boneset were long popular considered by physicians as the treatment of choice for with American physicians for colds and flu in spite of the malaria in the early 19th century. Quinine, isolated from disagreeable taste and nauseating effect. In one of the the bark in 1820, was a helpful refinement in making first published references on its use as an medicinal plant, this bitter remedy more acceptable to the public. In 1824 Manasseh Cutler wrote in 1784 of the infusion being Dr. John Sappington bought all of the quinine available used as a powerful emetic (Cutler 1903). In 1787 J.D. in Philadelphia and brought it back to Missouri in his

J AHG Journal of the American Herbalists Guild Volume 9 Number 1 15 MATERIA MEDICA

saddlebags. While accepted by many, the general efficacious. If taken in large quantities or in short populace in that area was slow to abandon the use of intervals it produced sudden vomiting. Giving emetic boneset. In 1844 in his book, Theory and Treatment of doses in break-bone fever appeared beneficial. In colds Fevers, he stated that boneset was one of the best and influenza with rheumatic components, it effectively indigenous substitutes when quinine was unavailable or relieved the discomfort in the limbs. As a rectal injection, in short supply in malarious districts (Hall 1974). it provided effective laxative results (Cook 1985). In 1828 the noted naturalist C.S. Rafinesque stated that boneset acts powerfully on the skin for obstinate cutaneous diseases. Otherwise, he confirms its use for fevers such as malaria, as an emetic when the warm decoction is given in large doses, and as a powerful tonic as a cold preparation. Only its nauseous and disagreeable taste prevented its general use (Anon. 1918). In two independent updates of the original USP, the Philadelphia 1st revision included thoroughwort herb in its primary list (USP 1831), while the New York 2nd edition noted the virtues of thoroughwort or boneset were extracted by water (USP 1830). Bowker’s Family Instructor of 1836 advised use of a strong tea drunk freely before going to bed to eliminate mild colds. The finely powdered leaves mixed with molasses were recommended as a gentle purge or, when steeped and drank cold, to correct the bile (Anon. 1918). The USPs of the mid-19th century continued to include the tops and leaves of thoroughwort in the primary list along with instructions for preparing the infusion (USP 1842 & 1851).

Physiomedical applications, preparations, and doses Samuel Thomson declared this herb to be warming and good for coughs and other lung complaints when used as a common drink. Besides its expectorant activity, he noted it was also a mild emetic, diaphoretic, and tonic (Anon. 1918). A botanical physician’s use of this remedy depended on the form utilized. As a cold infusion, it proved to be a soothing and relaxing tonic for dyspepsia. In this regard it also acted as a mild stimulant to the liver and bowels, increasing bile secretion and providing a comfortable a laxative effect. Its actions were described as slow and mild but persistent and reliable. In aching throughout the lungs and for chronic coughs with irritation the infusion was found to have a soothing © Martin Wall effect, whether prepared cold or warm (Cook 1985). Its most common use as a warm infusion was for its Eupatorium perfoliatum (boneset) diaphoretic effect. Used as such to promote sweating in fevers, it retained its laxative activity and proved doubly

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In his classic 1869 text, The Physio-Medical to a pint of boiling water. Doses of a wineglassful (2 oz.) Dispensatory, Dr. William Cook further described were to be drunk every half hour while the patient preparing water extracts by infusing one ounce of remained in bed. When 4-5 doses result in profuse powdered leaves and flowers in one quart of boiling persperation and possibly vomiting, relief is rapidly water. From 1-3 ounces of this were given per dose and obtained. The infusion is then given in small repeated repeated according to the desired effects. A solid extract doses. Charles Millspaugh, M.D., claimed in his 1887 was prepared by boiling down the decoction and was American Medicinal Plants that it was unlikely that any taken as a relaxing tonic in doses from 325-650 mg three herb in American domestic practice was used more times daily. It was also used as a base for other powdered extensively or frequently than boneset (Anon. 1918). By herbs. Cook believed the fluid extract to be fully effective 1890 Eupatorium perfoliatum fluid extract had become in representing the plant’s qualities. One pound of official (USP 1893). boneset was macerated in one quart of 50% alcohol. Transferred to a percolator, half a pint was collected as a Eclectic report on the cold infusion percolate out and was set aside. Warm water was added Dr. Joseph Adolphus reported on the value of treating in the percolator until the herb was exhausted. This intestinal problems with the cold infusion in doses that dilute aqueous percolate was evaporated to eight ounces did not cause vomiting or purging. He claimed that and then added to the first half pint of hydroalcoholic boneset diminished the secretion of the mucous glands ...it was unlikely percolate and filtered. The dose of this 1:1 extract was of the intestinal tract when their action was excessive. He 20-30 drops three or more times daily (Cook 1985). also believed that there was a strong association between that any herb nervous system dysfunction and the digestive in American Broad medical acceptance derangements. These he described as deficient domestic practice Besides the inclusion of Eupatorium perfoliatum in The innervation reflexly caused by local capillary inadequacy. Physio-Medical Dispensatory (Cook 1985) and all 19th He ascribed functional dyspepsia to hyperemia of the was used more century USPs (Boyle 1991), King’s and Newton mucous membranes and felt boneset given in the early extensively described its use in the Eclectic Dispensatory of 1852. stages was the best remedy. His preferred extract that or frequently They specified that, combined with potassium bitatrate preserved well was made by soaking eight ounces of the than boneset... and camphor, the powdered leaves were serviceable in green leaves in twelve ounces of soft water and four some cutaneous diseases. In addition, they listed the ounces of glycerin for two weeks, straining and pressing. usual applications of the cold infusion or extract as tonic This extract could be used externally for skin for typhoid fevers, dyspepsia, and general debility, and inflammation and ulcerations as well (Adolphus 1873). the warm infusion as diaphoretic and emetic for fevers, Dr. Adolphus described a case of a skeletal patient catarrhs, and cold (Anon. 1918). who had been dyspeptic for years and was unable to hold In his 1867 book New Remedies, the homeopathic down food. After eating he would experience intense professor E.M. Hale, M.D., of Hahnemann Medical acidic belching, his heart raced to 160 beats per minute, College, indicated this plant was useful for influenza and a precordial constriction accompanied by intense with pain in the back and limbs. Due to the multiple anxiety ensued. These symptoms would be relieved in effects and uses of the herb, he described it as a several hours as vomiting of the partially digested food “polychrest” that influences the whole organism in a took place. The man had been treated by numerous general manner. John Scudder in his 1871 Eclectic digestive medications (e.g., bismuth, ipecac, pepsin, classic Specific Medication and Specific Medicines bitter tonics, potassium iodide, quinine, morphine, described the best indications as a frequent, full pulse sodium sulphate), all of no benefit. Dr. Adolphus and flushed skin inclined to be moist, while throbbing prescribed a boneset extract made by soaking one ounce pain was the indication for local use (Anon. 1918). of the green leaves in a quart of soft water at 80°F to In their book Medicinal Plants published in London which two ounces of glycerin had been added. His diet in 1880, Bentley and Trimen described preparing the was Graham (whole wheat) mush and milk. The man, infusion for influenza. One ounce of the herb was added after taking four ounces of the boneset extract every four

J AHG Journal of the American Herbalists Guild Volume 9 Number 1 MATERIA MEDICA 17 AHG J Capsicum Journal of the American Herbalists Guild Volume 9 Number 1 Volume Mundy noted that the cold infusion in small doses noted that the cold infusion Mundy to unresponsive cases of malaria that were In In 1918 Lloyd Brothers made a new Colloidal Brothers 1918 Lloyd In that failed he gave 15 drops of boneset fluid extract in of boneset 15 drops he gave that failed was rapid, and the everyhot water 1-2 hours. Relief in 2-3 hours, returned The hiccough stopped. remedy finally only once or twice daily then after 6-8 hours, and 1908). A (Ellingwood disappearing entirely before hiccoughs in an old man in similar case of intractable when 15 which every had failed was cured prior remedy to of boneset fluid extract was added drops infusion and given hourly (Ellingwood 1994). hourly (Ellingwood infusion and given warm in given The infusion tonic. acted as a simple bitter and anti-malarial, and in larger doses was diaphoretic larger doses it acted as an emetic and cathartic.even He tonic and antimalarial. a digestive the tincture considered was 1- Medicine for the Specific The dose he recomended The infusion was at such times 1905). (Mundy 60 drops 1901), though (Bloyer superior to the tincture considered The bitterness of the infusion made it this was disputed. 1924). unacceptable to some (Felter the use of boneset was most quinine or had relapsed, and especially when general sluggishness effective, particularly predominant, intense aching were with other browache intermittent headache or severe Locke Dr. The Eclectic symptoms of ague. infusing one ounce in a quart of boiling recommended everywater and giving a half to a full teacupful 15 The patient was then put ensued. minutes until vomiting doses for two with smaller to bed and kept sweating hours. After drying was the patient, this treatment and stimulants (Ellingwood with other tonics followed 1928). 1994, Powers Lloyd’s colloidal preparation Lloyd’s Dr. was described by Eupatorium Medicine Specific in rheumatism. He par excellence as a remedy Bloyer claimed the chief indication was sluggishness (Bloyer general aching continued to be 1901). Deep-seated, indication for the use of as the prominent regarded pain in the muscles and bones, in the boneset; severe or head, in the chest, in the limbs and back, aching eyes, The skin was usually body. the entire over soreness 1901, described as moist and the pulse as full (Bloyer 1905). 1924, Mundy Felter it for the recommending Eupatorium, Medicine Specific , but when Capsicum The fluid extract was employed by Ellingwood in a Ellingwood by The fluid extract was employed Scudder declared that boneset occupied a front rank that boneset occupied a front Scudder declared in the Eclectic indigenous remedies but was little used indigenous remedies in the Eclectic doses as because of the unpleasant practice of using large would later mix only 10-30 He was formerly popular. a in four ounces of water and give of the tincture drops every of teaspoonful of this mixture hour (0.3-1.0 drop This was used for many rheumatic hourly). tincture conditions, especially in cases of chest pain and cough or the skin he believed obtain the best results, To fever. and tending toward must be full (not dehydrated) the tongue and pulse as also described perspiration. He pain, brief description of a patient with “dull full. His was one inclination to sweat” full tissues, leaden color, best (Scudder 1875). for whom boneset would work case of severe an interesting larger dose to resolve exhaustion from hiccoughs. A patient with extreme the intestinal inflammation and hemorrhage resembling had later stage of fatal typhoid, but with less fever, The tongue and hiccoughs for four days. from suffered mouth had a dry red membranous coating with a dark of first tried an infusion base. He John Scudder first described boneset used as an “essential Scudder first described boneset John The Medicines). of Specific (his early version tincture” was the much smaller doses of using this form advantage to the amounts of the infusion normally compared dried herb was ounces of the recently consumed. Eight in doses with one pint of 50% alcohol. Given tinctured the skin through excretion of one teaspoon, it increased for respiratory infections. In as a nauseant diaphoretic to stimulate the it was believed as 5 drops, doses as low visceral functions nervousvegetative and improve system (Scudder 1862a & 1862b). Small doses and specific prescribing Small doses and specific prescribing of Eclectics hours for one day had remarkably reduced symptoms. reduced day had remarkably hours for one abated and never entirely days his “spells” After four a for ten days he experienced However, returned. extremities his upper and lower nervous agitation over on sweating ended with profuse for 15-20 minutes that was The treatment abdomen. the palms, soles, and at which time his disposition continued for six weeks, his countenance was and composed, was serene and his formerly constipated bowels rejuvenated, 1873). (Adolphus functioned with regularity 18

same indications. This followed isolation of two distinct quinine sulphate, and opiates that were typically component complexes of entirely different chemical prescribed (Powers 1928, Best 1928). qualities and pharmacological effects. One was For acute aching with chilliness, depression and pleasantly bitter and soluble in water, alcohol, glycerin or subnormal vitality that characterized the first stages of syrup. It possessed the diaphoretic and tonic qualities influenza, boneset was considered one of the top useful in influenza, coughs, and colds. This was found remedies (Best 1928). In a discussion of this remedy for present in the dried herb, infusions, decoctions, and the flu, a Dr. Bixel claimed that in 1918 he lost only two alcoholic extracts. The other complex contains oils, fats, of 500 influenza cases he treated. A Dr. Ilgenfritz stated and glycosides insoluble in water, glycerin or syrup but that he treated 628 cases and lost only three using the very soluble in alcohol. It is found in all tinctures and infusion. He had his druggist make up a half-dozen one- fluid extracts, hot decoctions and the fresh infusion, but gallon bottles of infusion daily that he carried in his car is largely cast down as a precipitate when water extracts (Powers 1928). are cooled and allowed to sit for 12 hours. Though not Specific Eupatorium became a routine treatment of bitter, this complex is nauseating and also produces the influenza, taking its place alongside vaccines and serums cathartic action of boneset. The wine-colored Colloidal (Powers 1928). In the aged and debilitated Specific Specific Medicine retained the fragrance and mild herb Eupatorium helped bring relief to coughs with abundant flavor but excluded the second complex, flavone secretions that could not be expelled. It was also used for derivatives, and glucosides such as rutin. It could be the cough of measles (Bloyer 1901, Felter 1924). It was mixed with water, glycerin, and/or alcohol. This considered admirable in breaking up the common cold, Colloidal Specific Medicine was found to be especially but in children needed to be administered in an aromatic useful as a treatment and especially as a preventative in syrup. It relieved the pleuritic pains and those associated the influenza epidemic of 1918 (Anon. 1918). with the cough of broncho-pneumonia (Felter 1924). In these types of cases it acts both as a diaphoretic and Influenza epidemics expectorant (Best 1928). Boneset was often given in combination with complementary remedies (Cook 1985). One formula Use diminishes and antibacterial activity used by Dr. Hoener to cure over 700 cases in the flu discovered epidemic of 1891 contained 1.5 ounces each of elixirs of Eupatorium perfoliatum and its infusion had been official boneset and E. alternifolium (false boneset), along with from the first edition of the USP in 1820 through the 1.0 ounce each of Verbena hastata, Leptandra virginica, eighth revision in 1900 (Boyle 1991). Due to the growing and Agrimonia eupatoria. Used alternatively as a professional disregard for many herbs, but in recognition decoction, these quantities of dried herbs could be of its continuing popular utilization, it was transferred extracted with 6 pints of boiling water and given as 2-4 from the USP to the National Formulary (NF). tablespoon doses every 2-3 hours (Nowell 1926). By the 1920s naturopathic physiomedical use as The consensus among Eclectic physicians was that described by Dr. Nowell in the Dominion Herbal boneset was one of the safest and most successful College postgraduate course had not changed remedies employed during flu epidemics, especially the significantly from former times. The cold infusion was severe influenza pandemic from 1918-19. Both the valued for its tonic properties, good for ague and infusion and Lloyd’s Specific Eupatorium were effective. dyspepsia, and as a mild laxative when constipated. The Eventually, boneset began to be used as a prophylactic. warm infusion was diaphoretic and invaluable in colds, Cases were milder, the severe pain in the back and limbs fevers, and asthma. Its effect on the liver and bowels was was quickly relieved, cough and irritation were reduced, marked. Large warm doses produce emesis. Boiling the and recovery hastened with its liberal use (Powers 1928, decoction down, a solid extract could be made and rolled Felter 1924, Best 1928). The simple infusion of the into pills that helped reduce night sweats of tuberculosis. leaves and flowers was found to be safer and of greater The solid extract was not as relaxing but did act as an advantage than the bacterins, coal-tar compounds, antispasmodic (Nowell 1926).

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The physiomedicalist Dr. William Cook has stated stigmasterol were discovered from this species, along in 1689 that the dose of the powder would be from 0.65- with the triterpenes including alpha-amyrin and others 1.3 grams (10-20 grains), but that it was not given in (Dominguez et al 1974). An ethyl acetate fraction of a that form (Cook 1985). E. perfoliatum retained in the methanol and water extract of the herb contained 6 NF through the 8th edition published in 1946. The dose caffeic acid derivatives. These included chlorogenic of the powdered leaves and flowering tops was given acid, neochlorogenic acid, 3,5-dicaffeoylquinic acid, there as 2 grams or about 30 grains (NF 1946). and 3 new depsides of caffeic acid with glucaric acid Following World War II and the expansion of the (Maas et al 2008). synthetic pharmaceutical industry, boneset was relegated to the growing group of traditional remedies unused by Medical and pharmacological studies most professional prescribers. A clinical study using boneset was published in Germany An early antimicrobial study found the ether extract in 1981. The trial involved a comparison of the effects of of E. perfoliatum fresh plant produced complete to aspirin with a homeopathic dilution (D2) of Eupatorium partial inhibition of Staphylococcus aureus culture in vitro perfoliatum when used to treat the common cold. This (Carlson et al 1948). E. perfoliatum was shown to be one D2 preparation is a 1:100 dilution of the mother of the more active antibacterial plants of the 209 tincture made from the plant. Ten drops or two tablets of obtained from Nova Scotia that were studied. Ten grams this remedy were taken five times daily (amounting to of stems, leaves, flowers, and roots were macerated in 50 one half drop daily of mother tincture) by ten men and Following World ml of water for 5-10 minutes. The water extract was twelve women, while one aspirin tablet was taken three War II ... boneset filtered off and combined with the fluid pressed from the times daily by 14 men and 17 women. The effects were was relegated plant material. The extracted plant material was then assessed on day 1, 4, and 10 by reported subjective to the growing extracted again with 95% ethanol, filtered and pressed. complaints and physical examinations. Symptoms, body This procedure was then repeated with the solvents ethyl temperature, and lab findings were not significantly group of ether, acetone and benzene. When tested for inhibition different between the groups, indicating equivalent traditional of bacteria the water, alcohol, ether, and acetone extracts efficacy (Gassinger et al 1981). This dosage is more than remedies unused all produced inhibition of Staph. aureus (diameter of ten times less than even Scudder’s relatively low inhibition 16, 12, 23, and 17 mm, respectively) but not recommended daily dose for his essential tincture in by most of Escherichia coli (Bishop & MacDonald 1951). febrile respiratory infections (Scudder 1875). professional Subsequent laboratory investigations into boneset’s prescribers. analysis pharmacological effects began in earnest in Germany. Scientific interest in boneset appeared dormant for The sesquiterpene lactone eufoliatin has been shown to decades until phytochemical studies on this plant began enhance phagocytosis by neutrophils in a in the 1970s. isolated from E. perfoliatum chemiluminescence immunostimulation assay (Wagner methanolic extract of the aerial parts include the et al 1985b). A screening test of Eupatorium perfoliatum glycosides hyperoside, astragalin, rutin and kaempferol water and alkaline-water extracts of the leaves and their rutinoside (Wagner e al 1972). A number of isolated heteroglycan polysaccharides showed sesquiterpene lactone components were isolated from significantly enhanced phagocytic activity in vitro and in Eupatorium spp. including E. perfoliatum (Bohlmann et vivo (Wagner et al 1984, Wagner et al 1985a). al 1977). Two of these are germacranolides, euperfolin Phagocytosis was stimulated in human granulocytes in and euperfolitin, identified along with the vitro at a concentration of 0.001 mg/ml (Wagner et al diepoxyguianolide, eufoliatin, and a novel dilactone, 1985a). Two homogeneous polysaccharides were isolated eufoliatorin (Herz et al 1977). from the alkaline aqueous extract by ethanol Terpene derivatives, known as chromenes, were precipitation and shown to be 4-0- isolated from E. perfoliatum and related species methylglucuronoxylans with Mrs of 40,000 and (Bohlmann & Grenz 1977). The sterols campesterol, >500,000. These polysaccharides showed a phagocytosis- beta-sitosterol (Hooper & Chandler 1984), and enhancing effect in carbon clearance, granulocyte-, and

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chemiluminescence tests (Vollmar et al 1986). The respiratory infections, and febrile conditions, and its immune-enhancing effects could be valuable in treating action to enhance stomach and liver secretions. The infections, especially viral. usual fluid extract dose is 30 minims or 2 ml (Priest & In combination with Echinacea angustifolia extract, Priest 1982). David Hoffman noted its speedy relief of E. perfoliatum extract helps increase phagocytosis in the the associated aches and pains and clearing respiratory carbon-clearance test more than the E. angustifolia mucosal congestion. Its cleansing laxative action and extract alone. Furthermore, with the successive additions symptomatic relief of rheumatism make it a good general of Baptisia tinctoria extract and Arnica montana extract agent outside of acute febrile conditions. His tincture to this combination, the phagocytosis was incrementally dose is 2-4 ml three times daily. Collected in late summer increased as indicated in both the granulocyte and or early fall after the flowers open, 1-2 teaspoonsful of carbon-clearance tests. The four-extract combination the dried herb per cup infused for 10-15 minutes makes was over 50% more effective than the E. angustifolia a tea to be drunk hot every half hour for fevers or flu mono-extract (Wagner & Jurcic 1991). In another (Hoffman 1996). antibacterial test the crude ethanolic extract was mildly The naturopathic profession in America adopted antibacterial against the Gram-positive species Staph. the traditional physiomedical and Eclectic indications aureus and Bacillus megaterium but not the Gram- for boneset’s use, utilizing either the infusion, tincture negative E. coli or Pseudomonas aeruginosa (10-40 drops), or, while it was available, the Specific (Habtemariam & Macpherson 2000). Medicine (5-60 drops). The hot infusion was used as a A combination of mother tinctures of E. diaphoretic and mild laxative to dissipate colds in their angustifolia (40%), boneset (40%), and Thuja incipiency. Its sedative effect on aching tendencies was occidentalis (20%) was given in 3 ml daily doses orally for applied not only for influenza but also rheumatoid 4 weeks to 23 surgically-cured malignant tumor patients. conditions. In measles it helped bring out the rash and However, blood samples taken before treatment and control the cough. In moderate doses (1 teaspoon of the after two and four weeks of therapy showed no cold infusion 3-6 times daily) it acts as a bitter stomachic significant alteration in lymphocyte cytokine production tonic for improving the appetite and digestion. Hot compared to pretreatment levels or to blood samples infusions are nauseating and emetic if too strong, so cold from 12 surgical tumor patients used as a control. Also, infusions or alcoholic extracts are considered preferable no significant change in leukocyte populations was when its diaphoretic effects are not desired. identified at this dose when compared to pretreatment Administering in a palatable vehicle is best for children levels (Elsasser-Beile et al 1996). and delicate subjects (Kuts-Cheraux 1953, Lust 1974). Dr. Bill Mitchell obtained much traditional Modern British herbalists’ and naturopathic botanical knowledge from his mentor, the eclectic applications naturopathic doctor John Bastyr. Dr. Bastyr described By the 1980s British herbalists and naturopaths were the flowering tops and leaves of boneset as an excellent teaching the combined use of boneset for acute fevers diaphoretic and one of his favorite flu remedies, using ¼ and for flu with night sweats and aching bones together of standard tea every half hour until sweating begins. Dr. with Achillea millefolium (yarrow) in the first stage and Mitchell gave 30 drops of tincture four times daily in hot Anemone pulsatilla in the third stage. Post-influenzal water, considering it one of the finest flu remedies. He gastric upset and constipation could also be treated with also combined it together with elder (Sambucus spp.) boneset, Chelone glabra (turtlehead) and Juglans cinerea flowers and buds. For fevers such as typhoid or yellow (butternut) syrup. It was also combined with Asclepias fever, sip wineglass doses until the fever is reduced or use tuberosa (pleurisy root) and Inula helenum (elecampane) 15-40 drops of the tincture. As a stimulating stomachic for pulmonary inflammation with cough and soreness tonic, the cold tea twice daily or 10 drops of the tincture (Priest & Priest 1982). in a cup of cold water may be used. A dose of 5-60 drops The emphasis of professional British herbalists has of tincture serves as a stomachic that benefits dyspepsia been in using boneset for influenza epidemics, and people who cannot keep food down. He further

J AHG Journal of the American Herbalists Guild Volume 9 Number 1 21 MATERIA MEDICA

recommended 150 drops of tincture (comparable to the violent vomiting, and severe constipation. The syndrome Eclectic dose of 3 cups of strong tea) to induce emesis if also involves blood glucose changes and severe ketosis that was desired (Mitchell 1982 & 2003). (Woerdenbag 1993). Drying the plant reduces the tremetol toxicity (Spoerke 1980). Concern has been Possible adverse effects expressed in relation to its supposed similarity in The obvious side effects from excessive consumption of appearance to E. perfoliatum (Woerdenbag 1993). boneset are the vomiting and diarrhea. Vomiting occurs Both of these species can be found from Canada more readily when the tea is taken hot. Diarrhea occurs south through the eastern, midwestern, and Great Plains after 6-7 hours and is accompanied by profuse sweating. states to the Gulf of Mexico. However, as noted earlier, Since these effects are sometimes the purpose for which E. perfoliatum leaves are lanceolate, wrinkled, and boneset is taken, they are not in that case considered perfoliate, that is, the stem appears to puncture the adverse events. Vomiting appears to be due to the flavone middle of the pairs of opposite leaves. The opposite eupatorin, which also has cytotoxic effects (Woerdenbag leaves of E. rugosum on the other hand are heart-shaped 1993). The ethanolic extract of the dried leaves was also with toothed margins and rest on slender petioles (Foster overtly cytotoxic to the three mammalian cell lines tested & Duke 1990). Whatever unnecessary confusion existed (Habtemariam & Macpherson 2000). The cytotoxic between these species was exaggerated when a text on activity may also be due to its sesquiterpene lactones, but herbal medicines identified both E. perfoliatum and E. this has not been validated (Woerdenbag 1993). rugosum as boneset, or alternatively richweed and white Boneset should be used with caution when allergic snakeroot. This text stated that E. rugosum was “the most hypersensitivity to Composite family plants exists, since toxic member of the group” but that it was hard to this may result in contact dermatitis from the differentiate it from other species, failing to distinguish it sesquiterpene lactone constituents that are common in from E. perfoliatum morphologically or phytochemically the Eupatorium genus (Woerdenbag 1993). Though (Spoerke 1980). Unfortunately, this error of mistaken most Eupatorium spp. have been shown to contain association was perpetuated in early editions of my own hepatotoxic pyrrolizidine alkaloids, these have not been clinical toxicology handbook (Brinker 1989). isolated from E. perfoliatum. Uncharacterized alkaloids have been reported (Locock 1990, Woerdenbag 1993). Conclusions The plant is known to contain high amounts of The bitters in boneset have tonic effects on the nitrate that has been considered responsible for alimentary tract and digestion. Increases in both spontaneous abortions that occur in cattle grazing on secretions and motility are common physiologic this plant. Free nitrate ingestion leads to methemoglobin responses to bitter botanical compounds. The prevalent formation and tissue anoxia that can precipitate a use of boneset by native Americans and pioneers for miscarriage (Locock 1990, Sund et al 1957). So its use is common febrile conditions such as malaria could be preferably avoided during pregnancy, due to its potential explained by its diaphoretic effect of controlling fever fetotoxic, cathartic, and abortifacient effects produced by through sweating. This does not, however, explain its consumption of large amounts. ability to dramatically relieve the associated body aches in these conditions. Unnecessary confusion Its ability to protect against viral diseases such as The species E. rugosum, know commonly as white influenza may be attributed at least partially to an snakeroot or richweed, has been designated by the FDA enhancement of nonspecific immune resistance. The tea as a poisonous plant, since it caused many deaths in the provides a proper extract for the polysaccharides that 19th century. It is noted for its unique component have been shown to actively improve phagocytosis. tremetol that is responsible for stock poisoning and milk However, the tinctures that have been popularly used sickness in those consuming milk, butter, or possibly and tested are also known to be effective in these even meat from livestock that have grazed on this plant. conditions, possibly due to the sesquiterpene lactone Symptoms of milk sickness include anorexia, tremors, eufoliatin that contributes to an immune-enhancing

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effect. It may be other sesquiterpene lactones or Habtemariam S & Macpherson AM 2000, Cytotoxicity and undiscovered phytochemical components that make this antibacterial activity of ethanol extract from leaves of a herbal drug, boneset (Eupatorium perfoliatum) Phytother plant a special contributor to the management of Res. 14:575-577 common viral complaints. Inhibition of Gram-positive Hall TB Jr 1974, Eupatorium perfoliatum a plant with a history bacteria by water and ethanolic extracts is an additional Mo Med. 71:527-528 Herz W, Kalyanaraman PS, Ramakrishnan G 1977, feature that could contribute to treating or preventing Sesquiterpene lactones of Eupatorium perfoliatum J Org secondary infections caused by these organisms. Chem. 42(13):2264-2271 Hoffman D 1996, The Complete Illustrated Holistic Herbal. References Element Books: Boston, MA Adolphus J 1873, Eupatorium perfoliatum Ecl Med J. 31:451- Hooper SN & Chandler RF 1984, Herbal remedies of the 453 Maritime Indians: phytosterols and triterpenes of 67 Anonymous 1918, A Treatise on Eupatorium perfoliatum Drug plants. J. Ethnopharmocol. 10:181-194 Treatise No. XXXII. Lloyd Brothers Pharmacists, Inc.: Kuts-Cheraux AW (ed.) 1953, Naturae Medicina and Cincinnati, OH Naturopathic Dispensatory. American Naturopathic Best WP 1928, Eupatorium – Boneset. Ecl Med J. 88:93-94 Physicians and Surgeons Assoc: Des Moines, IA Bishop CH & MacDonald RE 1951, A survey of higher plants Locock RA 1990, Boneset Eupatorium Can Pharm J. 123:229- for antibacterial substances Can J Bot. 29:260-269 233 Bloyer WE 1901, Eupatorium perfoliatum Ecl Med J. 61:336-337 Lust J 1974, The Herb Book. Bantam Books: New York, NY Bohlmann F & Grenz M 1977, Naturally occurring terpene Maas M, Petereit F, Hensel A 2008, Caffeic acid derivatives derivatives. 82. Constituents from representatives of the from Eupatorium perfoliatum L Molecules. 14(1):36-45 Eupatorium group [German]. Chem. Ber. 110(4):1321- Mitchell W 1982, Naturopathic Applications of the Botanical 1329 (Chem Abs. 87:18971y) Remedies. self published: Seattle, WA Bohlmann F, Mahanta PK, Suwita A, et al. 1977, Neue Mitchell WA Jr 2003, Plant Medicine in Practice – Using the sesquiterpenlactone und andere inhaltsstoffe aus Teachings of John Bastyr. Churchill Livingstone: vertretern der Eupatorium-gruppe [German; Engl. abs.] Edinburgh, Scot., UK Phytochem. 16:1973-1981 Moerman DE 1998, Native American Ethnobotany. Timber Boyle W 1991, Official Herbs. Buckeye Naturopathic Press: Press: Portland, OR East Palestine, OH Mundy WN 1905, Eupatorium Ecl Med J. 65:572-573 Brinker FJ 1989, The Toxicology of Botanical Medicines 2nd ed. NF 1946 (Committee on the National Formulary), The National Eclectic Medical Pub: Portland, OR Formulary VIII ed. American Pharmaceutical Assoc.: Carlson JH, Douglas HG, Robertson J 1948, Antibacterial Washington, DC substances separated from plants J Bacteriol. 55:241-248 Nowell H 1926, Post Graduate Course, Dominion Herbal Cook WH 1985, The Physio-Medical Dispensatory [1869]. College: Vancouver, BC, Canada Eclectic Medical Pub: Portland, OR Powers HW 1928, Eupatorium perfoliatum Ecl. Med. J. Cutler M 1903, Vegetable Productions Naturally Growing in 88:167-169 this Part of America [1785] Bulletin No. 7. Lloyd Library: Priest AW & Priest LR 1982, Herbal Medication – A Clinical and Cincinnati, OH Dispensary Handbook, L.N. Folwler & Co Ltd: London, Dominguez XA, Quintanilla JAG, Rojas MP 1974, Sterols and Engl., UK triterpenes from Eupatorium perfoliatum. Phytochem. Scudder JM 1862a, Eupatorium perfoliatum Ecl Med J. 22:61 13:673-674 Scudder JM 1862b, Eupatorium perfoliatum Ecl Med J. 22:289 Ellingwood F 1908, Boneset for hiccough Ell Therapeut. Scudder JM 1875, Eupatorium perfoliatum Ecl Med J. 35:481- 2(12):393 482 Ellingwood F 1994, American Materia Medica, Therapeutics and Spoerke DG Jr 1980, Herbal Medications, Woodbridge Press Pharmacognosy [1919]. Eclectic Medical Pub: Sandy, OR Pub Co: Santa Barbara, CA Elsasser-Beile U, Willenbacher W, Bartsch HH, et al. 1996, Sund JM, Wright JM, Simon J 1957, Weeds containing Cytokine production in leukocyte cultures during therapy nitrates cause abortion in cattle Agronomy J. 49:278-279 with echinacea extract J Clin Lab Anal. 10:441-445 USP 1820 (Medical Societies & Colleges), Pharmacopoeia of Felter HW 1924, Eupatorium (Boneset) Ecl Med J. 84:200-202 the United States of America. Wells & Lilly: Boston, MA Foster S & Duke JA 1990, A Field Guide to Medicinal Plants – USP 1830 (General Convention for Formation of American Eastern and Central North America. Houghton Mifflin Co: Pharmacopoeia), Pharmacopoeia of the United States of Boston, MA America, 2nd ed. S. Converse: New York, NY Gassinger CA, Wunstel G, Netter P 1981, A controlled clinical USP 1831 (National Medical Convention), Pharmacopoeia of trial for testing the efficacy of the homeopathic drug the United States of America, 1st rev., John Grigg: Eupatorium perfoliatum D2 in the treatment of common Philadelphia, PA cold [German; Engl. abs.] Arzneim Forsch / Drug Res. USP 1842 (National Medical Convention), Pharmacopoeia of 31(4):732-736 the United States of America, 2nd rev. Grigg & Elliot:

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Philadelphia, PA Wagner H, Proksch A, Riess-Maurer I, et al. 1985a, USP 1851 (National Medical Convention), Pharmacopoeia of Immunostimulating polysaccharides (heteroglycans) of the United States of America, 3rd rev. Lippincott, Grambo, higher plants [German; Engl. abs.] Arzneim Forsch / Drug & Co.: Philadelphia, PA Res. 35(7):1069-1075 USP 1893 (National Convention for Revising Wagner H, Proksch A, Vollmar A, et al. 1985b, In vitro Pharmarmacopoeia), Pharmacopoeia of the United States of phagocytosis stimulation by isolated plant materials America, 7th rev. P. Blakiston, Son & Co.: Philadelphia, PA measured in the phagocytosis-chemoluminescence (CL) Vollmar A, Schafer W, Wagner H 1986, Immunologically model [German]. Planta Med. (2):139-144 (Chem Abs. active polysaccharides of Eupatorium cannabinum and 103:98436q) Eupatorium perfoliatum Phytochem. 25(2):377-381 Woerdenbag HJ 1993, Eupatorium species, in Adverse Effects Wagner H, Iyengar MA, Horhammer L 1972, Flavonol-3- of Herbal Drugs vol 2 (ed by DeSmet PAGM, Keller K, glucosides in eight Eupatorium species Phytochem. Hansel R, et al.). Springer-Verlag: Berlin, Germ. 11:1504-1505 Wagner H & Jurcic K 1991, Immunological studies of plant Wagner H, Proksch A, Riess-Maurer I, et al. 1984, extract combinations in vitro and in vivo studies on the Immunostimulating polysaccharides (heteroglycanes) [sic] stimulation of phagocytosis [German; Engl. abs.] Arzneim of higher plants / Preliminary communication [German; Forsch / Drug Res. 41(10):1072-1076 Engl. abs.] Arzneim Forsch / Drug Res. 34(6):659-661

The writings of Francis Brinker...

...are the fruit of decades of love and study (1989). Along with other original and prior of Herbal, Naturopathic, and Eclectic works, Native Healing Gifts, a book on plants medicines. Growing up on a farm in Kansas of the Southwest, was included in EDBT near Waconda Springs Naturopathic vol. 2 (1995). His book on botanicals in sanitarium, he earned a degree in biology Naturopathy (Formula for Healthful Living, at the University of Kansas. His knowledge 1995) was a product of teaching at the of herbs grew through exchanges with newly founded Southwest College of J. American Herbalist Guild (13, 2000-09), fellow students in the human biology Naturopathic Medicine (1993-99). Herb and Alternative Medicine Alert (9, 2003-09). degree program at Kansas Newman College Contraindications and Drug Interactions (1997), He also has been engaged writing, and the doctoral program at the National the first book of its kind, led to teaching in reviewing, and /or editing monograph’s college of Naturopathic Medicine in Dr. Andrew Weil’s Program in Integrative or articles for American Herbal Pharmacopeia Oregon, where he initiated a herbarium. Medicine (1998-2009). His personally (1994-2009), Eclectic Medical Journal Reprints His academic study culminated in a favorite text (Complex Herbs – Complete (1995-96), MicroMedex Alt. Med. database postdoctoral fellowship in botanical Medicines, 2004) focused on naturopathic (1998-2000), Integrative Medicine Select medicine at NCNM and publication of his perspectives, Eclectic contributions, and (2002), NIH ODS annual bibliography research on Botanical Toxicology (1983) while indigenous herbs. (2002-04), and ABC Herb Clips (2008-09). teaching Naturopathic botanical medicine Besides providing articles singly to in the clinic and classroom (1981-85). many journals, Dr. Brinker has contributed The writings of Francis Brinker, ND, While working at home in Arizona multiple extensive articles to each of several are available from Eclectic Medical to help raise his 4 children, he developed publications: Townsend Letter for Doctors Publications, www.eclecticherb.com/emp, an herbal repertory, To Health With Herbs. (3, 1989-93), J. of Naturopathic Medicine where he maintains a free online It was incorporated in the Eclectic (7, 1990-2000), British J. of Phytotherapy database of HCDI updates/additions. Dispensatory of Botanical Therapeutics, vol. 1 (6, 1992-97), HerbalGram (6, 1998-2009), (EMP orders 1-800-865-1487).

Volume 9 Number 1 Journal of the American Herbalists Guild J AHG