Herbal Monograph
Boneset
Eupatorium perfoliatum L.
Asteraceae (Compositae)
Premier American fever remedy for influenza with deep bone aches — short-term use only (PA content)
Overview
Plant Description
Robust, erect herbaceous perennial, 60–150 cm tall. Stems stout, cylindrical, hairy, typically unbranched below the inflorescence. The most distinctive morphological feature is the PERFOLIATE LEAVES: opposite leaf pairs are fused at the base so that the stem appears to pierce through the middle of a single, large leaf blade. Individual leaf blades are lanceolate, 10–20 cm long, 2–5 cm wide, serrate margins, rugose (wrinkled) upper surface, densely pubescent below, gradually tapering to an acute apex. This perfoliate leaf arrangement is the key identification feature and the origin of the species name 'perfoliatum.' Inflorescence a large, flat-topped to slightly dome-shaped corymb of 10–40+ small flower heads; each head containing 9–23 white, tubular disc florets (no ray florets). Flowers bloom July–October. Achenes small, 5-angled, with a pappus of bristles for wind dispersal. Root system a fibrous mat from a short, horizontal rhizome.
Habitat
Wet meadows, marshes, stream banks, ditches, swamps, moist woodland borders, and floodplains. A wetland indicator species that requires consistently moist to saturated soil. Often found in partial shade at pond edges, in wet prairies, and along waterways. Tolerates brief standing water but not permanent inundation.
Distribution
Native to eastern North America, from Nova Scotia and Manitoba south to Florida and Texas. Most common in the eastern deciduous forest region, Great Lakes states, and along the Atlantic and Gulf coastal plains. Wild-harvested from natural stands; some garden cultivation for pollinator habitat and medicinal use. Not commercially cultivated at agricultural scale.
Parts Used
Aerial parts (herb — leaf and flowering top)
Preferred: Dried herb for infusion/decoction; fresh plant tincture
The entire aerial portion (leaves, stems, flowers) harvested at flowering is the standard medicinal part. The perfoliate leaves are the most commonly used and the most easily identified part. Both fresh and dried herb are used; the Eclectics considered the fresh plant tincture superior. The dried herb retains efficacy for decoction and infusion. Properly identified material is essential — the perfoliate leaves are the diagnostic feature.
Key Constituents
Pyrrolizidine alkaloids (PAs)
SAFETY CONCERN — NOT THERAPEUTIC. The PA content in E. perfoliatum is generally considered lower than in high-PA species such as comfrey (Symphytum) or Senecio, but it is measurable and toxicologically relevant for sustained internal use. The German Commission E originally issued a positive monograph for boneset but later added PA cautions. The AHPA Botanical Safety Handbook classifies boneset as Class 2d due to PA content. All internal use should be duration-limited and the total PA intake from all herbal sources should be considered.
Sesquiterpene lactones
The sesquiterpene lactone fraction is a major contributor to boneset's immunostimulant and anti-inflammatory activity. These compounds activate macrophages, stimulate phagocytosis, and increase production of pro-inflammatory cytokines (useful in acute infection). The sesquiterpene lactones also contribute the intensely bitter taste that stimulates digestive secretions and may contribute to the emetic effect at higher doses.
Flavonoids
The flavonoid fraction contributes anti-inflammatory, antioxidant, and mild diaphoretic activity. Eupatorin is a distinctive marker compound for Eupatorium species. Quercetin and rutin provide complementary anti-inflammatory effects that support the traditional use for febrile illness with muscle aches.
Polysaccharides and other constituents
The polysaccharide fraction is especially important — the immunostimulant heteropolysaccharides provide pharmacological support for the traditional use of boneset to enhance immune response during acute febrile illness. These polysaccharides act through TLR4 signaling to activate innate immune responses. Combined with the sesquiterpene lactone-mediated immunostimulation, boneset has a dual immunostimulant mechanism.
Herbal Actions
Promotes perspiration
The primary traditional action and the basis for boneset's fame. As a warm/stimulating diaphoretic, boneset promotes sweating when given as a hot infusion during febrile illness. The Eclectic and physiomedicalist traditions considered it the premier diaphoretic for influenza-like illness with deep, aching bone and muscle pain. The mechanism involves peripheral vasodilation and enhanced perspiration. Traditionally given at the onset of fever to 'break' the fever and promote resolution of acute infection.
[3, 5]Stimulates and enhances immune response
Strong immunostimulant activity demonstrated in vitro and in vivo. The polysaccharide fraction stimulates macrophage phagocytosis, increases TNF-α and interleukin production, and activates innate immune pathways. The sesquiterpene lactone fraction provides additional immunostimulation. Gassinger et al. (1981) conducted a clinical trial demonstrating boneset comparable to aspirin for symptom relief in acute upper respiratory infection. The dual polysaccharide + sesquiterpene lactone immunostimulant mechanism is relatively unique among Western herbs.
[3, 4]Reduces inflammation
Anti-inflammatory activity from the flavonoid fraction (quercetin, eupatorin, rutin) and sesquiterpene lactones. Inhibits COX-2 and pro-inflammatory cytokines. Particularly relevant for the deep muscle aches and bone pain associated with influenza ('break-bone fever' was a colloquial name for influenza, and boneset's name may derive from treating this symptom).
[3]Stimulates digestive secretions via bitter taste receptors
Intensely bitter herb that stimulates digestive secretions, appetite, and gastrointestinal motility. The bitter quality comes from sesquiterpene lactones and the resinous fraction. At moderate doses, promotes digestion; at high doses, may induce nausea and vomiting (emetic effect).
[5]Promotes the discharge of mucus from the respiratory tract
Mild expectorant action facilitates expectoration of bronchial mucus during respiratory infections. Supports the overall use pattern of boneset as a comprehensive acute respiratory infection remedy.
[3]Relieves smooth muscle spasm
Mild antispasmodic and smooth muscle relaxant properties. May contribute to relief of intestinal cramping and bronchospasm during acute illness.
[3]Therapeutic Indications
Immune System
Influenza and acute febrile illness
The defining indication. Boneset was considered one of the most important herbs for influenza in American herbal medicine from the 18th through early 20th centuries. The common name may derive from 'break-bone fever' (dengue or influenza with severe myalgia). Gassinger et al. (1981) conducted a randomized clinical trial comparing a boneset preparation to aspirin in patients with acute upper respiratory infections, finding comparable efficacy for symptom relief. The herb addresses the full symptom complex of influenza: fever (diaphoretic), muscle/bone aches (anti-inflammatory), immune activation (immunostimulant), and respiratory congestion (expectorant).
[3, 4]Common cold and upper respiratory infection
Used for acute onset of common cold, particularly when accompanied by chills, body aches, and general malaise. Best indicated for the early stages of infection when immune stimulation and diaphoresis are most beneficial.
[3]Immune stimulation during acute infection
The polysaccharide and sesquiterpene lactone fractions have demonstrated significant immunostimulant activity in laboratory studies. Macrophage phagocytosis is enhanced, as is production of immune cytokines. This is NOT an herb for chronic immune tonification — it is for acute, short-term immune boost during active infection.
[3]Respiratory System
Musculoskeletal System
Influenza-associated myalgia and deep bone aches
The classic boneset indication: deep, aching pain in the bones and muscles during influenza or other febrile illness. This is the symptom that gives the herb its common name (treating the sensation that 'bones are breaking' during flu). The anti-inflammatory action from flavonoids and sesquiterpene lactones addresses this directly.
[3, 5]Digestive System
Poor appetite and sluggish digestion during illness
The intensely bitter taste stimulates gastric and biliary secretions. Used at moderate doses as a bitter tonic when appetite is suppressed during illness. At higher doses, boneset is emetic — inducing vomiting was actually a traditional therapeutic strategy ('heroic' medicine) that is largely obsolete.
[5]Energetics
Temperature
warm
Moisture
dry
Taste
Tissue States
cold/depression, damp/stagnation
Boneset is warm and drying — the prototypical energetic profile for an acute infection remedy in Western herbal tradition. The warming quality promotes circulation and sweating (diaphoresis). The drying quality helps resolve excessive mucus and congestion (damp/stagnation). The bitter taste stimulates vital force and digestive function. Specifically indicated for acute febrile illness with a sense of heaviness, achiness, and stagnation — the patient feels cold, achy, and stuck. Contraenergetically, boneset is poorly suited for dry, depleted, chronic conditions or for patients with hot, dry constitutions.
Traditional Uses
Native American medicine
- Widely used by multiple tribes throughout eastern North America for fevers and agues (malaria-like intermittent fevers)
- Delaware, Creek, Iroquois, Mohegan, and other tribes used boneset tea for fevers, colds, and influenza
- Used for intermittent and malarial fevers — Native peoples taught European settlers to use boneset as a fever remedy
- Applied externally as a poultice for pain and swelling
- Some tribes used the tea for digestive complaints and as a general tonic
"Native American use of boneset was the foundation for its adoption into colonial and early American medicine. The herb was one of the most important medicinal plants shared by Native peoples with European settlers. Moerman's Native American Ethnobotany records use by numerous tribal groups across eastern North America."
[6]
Eclectic medicine (American, 19th–early 20th century)
- Considered 'one of the most important of the indigenous American remedies' (Felter & Lloyd)
- Primary remedy for influenza ('break-bone fever') — the most used herb during influenza epidemics
- Given as a hot infusion at the onset of fever to produce copious sweating and 'break' the fever
- In larger doses, used as an emetic (to induce vomiting) — a now-obsolete practice of 'heroic' medicine
- Specific Eclectic indication: deep, aching pain in the bones and muscles during febrile illness
- Used for intermittent fevers (ague) when quinine was unavailable or poorly tolerated
- Given cold as a bitter tonic for sluggish digestion and debility after illness
- Combined with elderflower and peppermint for the classic influenza formula
"Felter and Lloyd in King's American Dispensatory (1898) describe boneset as 'probably the most extensively used of the indigenous medicinal plants of the United States... In domestic practice, boneset tea (hot) is one of the most popular of American remedies for colds, influenza, and allied maladies.' During the great influenza pandemics of the 19th century, boneset was among the most relied-upon herbal remedies in American households."
[5]
Western herbal medicine (modern)
- Continues as a key remedy for influenza and acute febrile illness in Western herbal practice
- Often combined with elderflower (Sambucus nigra), peppermint (Mentha piperita), and yarrow (Achillea millefolium) for acute influenza formulas
- Used as a short-term immunostimulant during acute infection — NOT for chronic immune support
- Recognized for dual diaphoretic + immunostimulant action that is uniquely suited to early-stage flu
- Modern practitioners are more cautious about dose and duration due to PA content and emetic potential at higher doses
"David Hoffmann in Medical Herbalism (2003) lists boneset as a key influenza remedy, noting its unique combination of diaphoretic, immunostimulant, and musculoskeletal anti-inflammatory actions that specifically address the influenza symptom complex."
[3]
Modern Research
Clinical trial — boneset vs. aspirin for acute upper respiratory infection
Randomized, controlled trial comparing a hydroalcoholic boneset preparation to aspirin for symptom relief in patients with acute upper respiratory infection.
Findings: The boneset preparation produced symptom relief comparable to aspirin for acute upper respiratory infection symptoms including fever, pain, and malaise. The study was conducted in Germany where Eupatorium perfoliatum has an approved therapeutic use. The boneset group showed faster onset of fever reduction when given as a warm preparation (consistent with the diaphoretic mechanism).
Limitations: Older study (1981). Small sample size. Published in German. The exact preparation, dose, and study methodology may not meet current standards for clinical trials. Difficult to replicate with standardized commercial products.
[4]
Immunostimulant polysaccharides — in vitro activity
The heteropolysaccharide fraction of E. perfoliatum has been tested for immune-activating properties in cell-based assays.
Findings: 4-O-methylglucuronoarabinoxylans from boneset significantly stimulate macrophage phagocytosis, enhance production of pro-inflammatory cytokines (TNF-α, IL-1, IL-6), and activate the NF-kB signaling pathway in macrophage cell lines. The immunostimulant activity is dose-dependent and is primarily localized to the high-molecular-weight polysaccharide fraction. This provides a pharmacological mechanism for the traditional immunostimulant indication.
Limitations: In vitro data only. The in vivo relevance of orally administered plant polysaccharides depends on their absorption and interaction with gut-associated lymphoid tissue (GALT), which is not fully characterized for boneset polysaccharides.
[3]
Sesquiterpene lactones — anti-inflammatory and cytotoxic activity
The sesquiterpene lactone fraction of E. perfoliatum has been tested for anti-inflammatory and anticancer properties.
Findings: Sesquiterpene lactones from boneset (eupafolin, euperfolitin, and related compounds) demonstrate significant anti-inflammatory activity through inhibition of NF-kB, COX-2, and iNOS. Some compounds show cytotoxic activity against human cancer cell lines at micromolar concentrations. The anti-inflammatory mechanism provides pharmacological support for the traditional use for musculoskeletal pain during febrile illness.
Limitations: In vitro data at concentrations that may not be achievable in vivo after oral administration. Cytotoxic activity in cancer cell lines does not necessarily predict anticancer efficacy in whole organisms.
[3]
Pyrrolizidine alkaloid content — analytical assessment
Analytical studies have assessed the PA content of E. perfoliatum aerial parts to quantify the hepatotoxicity risk.
Findings: E. perfoliatum contains low but measurable levels of 1,2-unsaturated pyrrolizidine alkaloids, primarily lycopsamine and intermedine (and their N-oxides). Total PA content is generally lower than in high-PA species like comfrey (Symphytum officinale) or Senecio species. However, any amount of 1,2-unsaturated PAs poses a cumulative hepatotoxicity and genotoxicity risk with sustained internal use. The German Commission E originally approved boneset for upper respiratory infections but recommended limiting internal use duration due to PA concerns.
Limitations: PA content varies by growing conditions, plant part, and analytical methodology. Limited large-scale surveys of commercial boneset products for PA content.
Homeopathic use and clinical evidence
Eupatorium perfoliatum is one of the most commonly prescribed homeopathic remedies for influenza, used in potentized (diluted) form.
Findings: In homeopathic practice, Eupatorium perfoliatum is a first-line remedy for influenza with deep bone aches, high fever, and restlessness. The homeopathic indications mirror the herbal indications. Several observational studies from India and Europe have reported benefit of homeopathic Eupatorium perfoliatum for influenza and dengue fever symptoms. Note: homeopathic preparations are highly diluted and do not carry the PA risk of herbal doses.
Limitations: Homeopathic evidence is controversial and does not meet conventional clinical trial standards. Included for completeness given the significant use of boneset in homeopathic practice.
[3]
Preparations & Dosage
Infusion (Tea)
Strength: 1–2 g per 250 mL
Pour 250 mL of boiling water over 1–2 g of dried boneset herb (leaf and flowering tops). Cover and steep for 10–15 minutes. Strain. The infusion is intensely bitter. FOR DIAPHORETIC EFFECT: drink hot. FOR BITTER TONIC EFFECT: drink at room temperature or cool.
1–2 g per cup. One cup hot, 3 times daily during acute illness. Maximum 6 g dried herb per day.
Every 2–4 hours during acute illness; 3 times daily for maintenance bitter tonic use.
Short-term use only: 3–7 days for acute illness. Do not exceed 2 weeks of continuous use due to PA content.
Not recommended for children under 12 due to PA content. Older children (12+): half adult dose under practitioner supervision.
The classic method of administration. For influenza: drink the infusion as hot as tolerable, lie under warm blankets, and allow sweating (traditional diaphoretic protocol). The extremely bitter taste is part of the therapeutic action but may induce nausea in sensitive individuals — sipping slowly is preferable to gulping. Adding honey improves palatability. Higher doses (4+ g per cup) may cause vomiting — this was historically intentional ('heroic' emetic therapy) but is not recommended in modern practice.
Tincture
Strength: 1:5, 45–60% ethanol (dried); 1:2, 60–75% (fresh plant)
Macerate dried boneset herb in 45–60% ethanol at 1:5 ratio. Fresh plant tincture: 1:2 in 60–75% ethanol. Macerate 4–6 weeks.
1–3 mL, 3 times daily during acute illness.
Every 2–4 hours during acute febrile illness; 3 times daily for short-term immune support.
Limit to 1–2 weeks.
Not recommended for children under 12.
The Eclectics preferred the fresh plant tincture (Specific Medicine Eupatorium) and considered it more effective than the dried herb. Tincture allows precise dosing and is convenient for formula work. The fresh tincture has a strong, distinctive odor and intensely bitter taste.
Decoction
Strength: 2–3 g per 300 mL
Add 2–3 g dried boneset herb to 300 mL cold water. Bring to a gentle boil, reduce heat, and simmer for 10 minutes. Strain.
One cup 2–3 times daily during acute illness.
2–3 times daily.
3–7 days maximum.
Not recommended.
Decoction extracts more of the polysaccharide fraction than infusion, potentially enhancing immunostimulant activity. However, some volatile constituents may be lost. Decoction may be better suited for the immunostimulant indication while infusion is better for the diaphoretic indication (drink hot).
[3]
Glycerite
Strength: 1:5, 60% glycerin
Macerate dried boneset herb in 60% vegetable glycerin. Steep 6–8 weeks.
3–5 mL, 3 times daily.
3 times daily during acute illness.
Short-term (1–2 weeks) only.
Not recommended under 12 due to PA concerns.
Alcohol-free alternative. Glycerite may extract fewer bitter sesquiterpene lactones than ethanol tincture, potentially reducing both the bitterness and some of the therapeutic activity. Still contains polysaccharides and some sesquiterpene lactones.
[3]
Capsule / Powder
Strength: Crude powdered herb, 500 mg per capsule
Dried, powdered boneset herb in capsules.
500 mg per capsule, 2–4 capsules daily (1–2 g total). For acute illness: up to 3 g daily.
2–3 times daily.
Limit to 1–2 weeks.
Not recommended.
Capsules bypass the intensely bitter taste, which may be an advantage for compliance but loses the bitter reflex stimulation that contributes to the therapeutic action. The diaphoretic effect is best achieved with hot liquid preparations.
[3]
Safety & Interactions
Class 2d
Other specific use restrictions apply (AHPA Botanical Safety Handbook)
Contraindications
Contains pyrrolizidine alkaloids which are teratogenic and cross the placental barrier. PA-containing herbs are absolutely contraindicated in pregnancy. Additionally, the strong emetic potential at higher doses could be harmful during pregnancy.
PAs and their metabolites are excreted in breast milk and may harm the nursing infant's liver.
PA-induced hepatotoxicity risk is increased in patients with compromised hepatic function.
Immature hepatic metabolism increases PA vulnerability. The emetic potential is also a concern in young children.
Cross-reactivity possible in patients with documented allergy to ragweed, chrysanthemums, daisies, or other Asteraceae family members.
Drug Interactions
| Drug / Class | Severity | Mechanism |
|---|---|---|
| Hepatotoxic medications (acetaminophen at high doses, methotrexate, isoniazid, valproic acid) (Hepatotoxic drugs) | moderate | Additive hepatotoxic risk from PA content combined with hepatotoxic drugs. |
| Immunosuppressant medications (cyclosporine, tacrolimus, azathioprine, mycophenolate) (Immunosuppressants) | moderate | Boneset's strong immunostimulant activity (polysaccharides, sesquiterpene lactones stimulate macrophages, TNF-α, interleukins) could theoretically counteract immunosuppressive medications. |
| Anti-emetic medications (ondansetron, metoclopramide) (Anti-emetics) | minor | Boneset's emetic properties at higher doses may antagonize the effects of anti-emetic medications. |
| Lithium (Mood stabilizers) | theoretical | Boneset has mild diuretic and diaphoretic effects that could potentially affect fluid balance and electrolyte status. Significant fluid loss from sweating could theoretically concentrate lithium levels. |
Pregnancy & Lactation
Pregnancy
unsafe
Lactation
unsafe
CONTRAINDICATED in pregnancy and lactation due to pyrrolizidine alkaloid content. PAs are teratogenic and are excreted in breast milk. The emetic potential at higher doses adds further risk during pregnancy.
Adverse Effects
References
Monograph Sources
- [1] Gardner Z, McGuffin M (eds.). American Herbal Products Association's Botanical Safety Handbook, Second Edition: Eupatorium perfoliatum. CRC Press, Boca Raton (2013)
- [2] German Commission E. Commission E Monograph: Eupatorium perfoliatum (Boneset). Bundesanzeiger (Federal Gazette), Germany (1998)
- [3] Hoffmann D. Medical Herbalism: The Science and Practice of Herbal Medicine. Healing Arts Press, Rochester, VT (2003) : 540
Clinical Studies
- [4] Gassinger CA, Wünstel G, Netter P. A controlled clinical trial for testing the efficacy of the homeopathic drug Eupatorium perfoliatum D2 in the treatment of common cold. Arzneimittelforschung (1981) ; 31 : 732-736
Traditional Texts
- [5] Felter HW, Lloyd JU. King's American Dispensatory: Eupatorium Perfoliatum. Ohio Valley Company, Cincinnati (1898)
- [6] Moerman DE. Native American Ethnobotany. Timber Press, Portland, OR (1998)
Last updated: 2026-03-23 | Status: review
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