Joe-pye

Joe-Pye Weed (Eutrochium purpureum and Related Species): A Comprehensive Reference

1. Identity: Botanical Classification, Names, and Natural Source

Taxonomy and Nomenclature

Until about 2000, joe-pye weeds were placed in the same genus as the thoroughworts (or bonesets, Eupatorium), but DNA evidence convinced botanists they were different enough to have their own genus, Eutrochium. Based on chloroplast DNA analysis published by Edward E. Schilling et al. in 1999, the Joe Pye weeds were again separated into their own genus, Eutrochium, as Eutrochium is the senior synonym of Eupatoriadelphus. In consequence, joe-pye weed was reclassified into the Eutrochium genus in 2004; prior to that, its genus was Eupatorium. Many older pharmacopeial, ethnobotanical, and scientific records continue to use the name Eupatorium purpureum.

The name Eutrochium is derived from the Greek words eu (well) and troche (wheel-like), the latter being a reference to the wheel-like appearance of the whorled leaves. The specific epithet purpureum means "purple" and refers to the flower color.

The genus comprises five closely related North American species, all referred to as joe-pye weed: Eutrochium dubium (coastal plain joe-pye weed), Eutrochium fistulosum (hollow joe-pye weed), Eutrochium maculatum (spotted joe-pye weed), and Eutrochium purpureum (sweet joe-pye weed, gravel root). These species were all previously assigned Eupatorium names, and the medicinal literature treats them somewhat interchangeably, though E. purpureum is the species most consistently associated with the common name "gravel root" in herbal commerce.

Common Names

Synonyms and common names in use include: Eupatoire Pourpre, Eupatoriadelphus purpureus, Eupatorium purpureum, Herbe de Joe Pye, Joe Pye, Joe-Pye Weed, Kidney Root, Purple Boneset, Queen of the Meadow, Raíz de Eupatorio, Roter Wasserhanf, and Trumpet Weed. The German common name Roter Wasserhanf (red water hemp) appears in Central European herbal literature.

Plant Description and Natural Habitat

Joe-pye weed is native to Southeast Canada and the central and eastern United States and is mostly found along roadsides, moist prairies, thickets, woodland borders, shaded riverbanks, and on wooded slopes. It has rounded clusters of pink or purplish flowers and leaves arranged in whorls on the stem, and is typically a tall, robust plant occurring in lowlands along streams. It normally grows 5 to 7 feet high but can reach 12 feet. With pinkish or purplish-tinged flowers and leaves arranged in whorls of 3–7 on the stem, other identifying characters include an erect growth habit, sharply toothed leaves to 8 or even 12 inches long, and flowerheads that have disk florets but no petal-like ray florets. The species hybridize widely in nature, making identification a challenge even for botanists.

Part Used and Commercial Forms

Parts used medicinally are the root and rhizome. The bulb, root, and parts that grow above the ground are all used to make medicine, though the root is considered primary. The roots are said to be the most potent part of the plant. Commercial preparations include dried root powder, root decoctions, water and alcohol tinctures, and capsules. When joe-pye weed is made into an alcoholic tincture, it is not uncommon for a resinous compound called eupurpurin to precipitate out of the liquid.

Gravel root (as the species was then known) was listed in the U.S. Pharmacopoeia from 1820 to 1842.

2. Historical and Traditional Use

The Eponymous Healer: Who Was "Joe Pye"?

The origin of the common name is contested. The most prevalent theory holds that the name refers to a Colonial-era Native American named Joe Pye, who is said to have used one of the species to cure typhus. Another account holds that Joe Pye was a nineteenth-century white "Indian theme promoter" who used the root to induce sweating in cases of typhus. The earliest use of this name in documented records dates to 1810–1820.

While the botanical origins of this name remain a mystery, research links it to Joseph Shauquethqueat, a Mohican tribal leader from the late 18th and early 19th centuries who used the name Joe Pye in dealings with colonizers. He is said to have lived in the mission town of Stockbridge, Massachusetts, between 1740 and 1785 and took Joseph Pye as his Christian name. His name has come down through oral tradition. Scholars have diligently tried to trace this legendary Indian herbalist and healer who supposedly befriended New England pioneers, but the name on the plant is really all that remains of him.

An alternative folk etymology holds that the name "jopi" or "jopai" was supposedly an early Native American word for typhus in the Native tongue.

Indigenous North American Use

Many different American Indian tribes found the herb useful. The Cherokee and Iroquois used it for urinary and kidney ailments. The Chippewa used it in a child's bath to help promote sleep. The Ojibwa made a decoction of the root and used it to wash a papoose, believing it would help the child become strong. The Potawatomi used its leaves in poultices for treating burns.

Native tribes used gravel root as a healing tonic, including for relieving constipation, washing wounds with a strong tea made from the root to prevent infection, and as a general tonic taken during pregnancy and after childbirth. Huron H. Smith, an ethnobotanist who worked with several North American tribes during the 1920s and 1930s, was told that the Meskwaki used the root as a sort of "love medicine," nibbling it when speaking to an intended. Spotted joe-pye weed (Eupatorium maculatum L.) was used similarly, with Native Americans using the root to induce sweating in typhus fever.

The primary traditional preparation among indigenous peoples was the decoction: decoctions (extracts resulting from boiling tissues down to concentrate desired compounds) made from E. purpureum were used to cure fevers.

Colonial-Era and Eclectic Medical Use

According to New England folklore, Joe Pye used this plant to cure fevers, and American colonists used this plant to treat typhus outbreaks. Later 19th-century Americans used it for kidney and urinary infections, and modern herbals still recommend the tea as a kidney tonic and as a diuretic.

In the 19th-century Eclectic medical tradition, gravel root was regarded as one of the most important herbs for renal and reproductive system health, especially for cases of urinary irritation, cystitis, and stone formation. According to herbal records, the root was used by eclectic practitioners in the treatment of chronic urinary disorders, hematuria, gout, and rheumatism.

Joe-pye weed herb was historically used as an herbal remedy for rheumatism, gravel (gallstones), and dropsy (fluid retention). Teas of the roots or tops were used as a diuretic, as well as for rheumatism, gout, fevers, diarrhea, respiratory disorders, and even impotence. The root was included in several 19th- and early 20th-century herbal pharmacopeias for kidney and bladder complaints.

The common name "gravel root" reflects the use of a root decoction to prevent the formation of kidney stones or to reduce the size of existing ones. The common name further reflects its main use as a diuretic used to treat urinary infections and stones ("gravel").

Traditional Preparations

Traditional preparation methods described in historical records include:

• Dried joe-pye weed root and flowers used by herbalists for a diuretic tea to relieve kidney and urinary problems; the infusion used to induce sweating and break a high fever.
• Infusion or decoction taken as 1 cup every 2 hours for excess uric acid; tincture taken as 5–15 drops in a cup of water; a cough syrup made of the blossoms and leaves, steeped and boiled down, with molasses added and then boiled to a syrup.
• Fresh leaves of joe-pye weed used by the Potawatomi to make poultices for healing burns.

3. Key Constituents and Active Compounds

Overview of Phytochemistry

A comprehensive 2015 review in Chemistry & Biodiversity (PubMed PMID 26460556) reported that the genus Eupatorium comprises nearly 1,200 species, and that reported constituents from the genus involve flavonoids, terpenoids, pyrrolizidine alkaloids, phenylpropanoids, quinonoids, essential oils, and other compounds — altogether more than 300 identified compounds.

Principal Constituents of E. purpureum (Gravel Root)

Documented constituents include volatile oil (approximately 0.07%), flavonoids (notably euparin), resin (eupurpurin), iron phosphate, potassium chloride, silica, calcium, sodium, acid phosphate, and pyrrolizidine alkaloids.

Additional phytochemical analysis has identified benzofurans, euparin, cistifolin, and euparone as key compounds. More specifically, further phytochemical analysis of the crude extract led to the isolation of three known benzofurans — euparin, euparone, 6-hydroxy-3β-methoxytrematone — and a new benzofuran, 5-acetyl-6-hydroxy-2-(1-oxo-2-acetoxy-ethyl)-benzofuran.

• Euparin: Euparin is described as yellow, neutral, and crystalline. It belongs to the benzofuran class of compounds and is considered one of the flavonoid-type markers of the species.
• Cistifolin: During routine screening of medicinal plants for small molecular weight inhibitors of cell adhesion, the crude ethanolic extract of the antirheumatic herbal drug gravel root was identified as a potent inhibitor of some beta-1 and beta-2 integrin-mediated cell adhesions. The active principle was isolated and identified as 5-acetyl-6-hydroxy-2,3-dihydro-cis-2-isopropenyl-3-tiglinoyloxybenzofuran.
• Eupurpurin: Eupurpurin is an oleoresin that is precipitated from an alcoholic tincture of the herb.
• Pyrrolizidine alkaloids (PAs): In subterranean plant material, pyrrolizidine alkaloids are present. A great number of flavonoids, also as glycosides, have been shown in Eupatorium species, often in low quantities.

Mechanisms of Action

The primary mechanistic research for E. purpureum centers on the benzofuran compound cistifolin and its effects on integrin-mediated inflammatory processes:

Previous laboratory reports revealed that cistifolin from the antirheumatic herbal drug gravel root showed activity both in in vitro and in vivo models of inflammation. Additional data demonstrated that, in addition to LFA-1 and other integrin-mediated leucocyte adhesions, cistifolin inhibits the Mac-1 (CD11b/CD18)-dependent monocyte adhesion to fibrinogen in a concentration-dependent manner.

In in vitro work, cistifolin inhibited integrin-dependent cell–cell and cell–protein interactions with EC50 values between 7–20 micrograms/mL. Administered orally two hours before induction of inflammation (in rat paw) by carrageenan, it inhibited edema formation in a dose (10 and 50 mg/kg)-dependent manner.

None of the other benzofuran compounds isolated — euparin, euparone, and 6-hydroxy-3β-methoxytrematone — were active in suppressing integrin-mediated monocytic U937 cell adhesions in vitro.

As a diuretic, the plant is traditionally understood to stimulate the flow of water and solutes, though the precise molecular basis of this diuretic action in humans has not been characterized in clinical research.

4. Scientific Evidence by Area of Use

4.1 Anti-Inflammatory and Antirheumatic Activity

Preclinical (in vitro and animal) evidence: The most substantive published science for joe-pye weed / gravel root relates to the anti-inflammatory properties of cistifolin, investigated primarily by S. Habtemariam in a series of laboratory studies. An animal study (Habtemariam, 1998) demonstrated that Eupatorium purpureum reduced carrageenan-induced rat paw edema at doses of 10 and 50 mg/kg in a dose-dependent manner. In vitro studies suggest that cistifolin inhibits integrin-mediated leucocyte adhesion, specifically targeting integrins like Mac-1 (CD11b/CD18).

Clinical (human) evidence: Clinical trials are limited, and most evidence relies on traditional use. The quality of available evidence is generally low due to the lack of rigorous clinical studies. There is no good scientific evidence to support the use of gravel root for any condition based on controlled human trials.

Evidence strength: Preclinical only. The anti-inflammatory mechanism is plausible based on in vitro and animal experiments, but no controlled human trials have been conducted. Results cannot be extrapolated to clinical efficacy.

4.2 Urinary Tract Health, Kidney Stones ("Gravel"), and Diuresis

This is the area for which joe-pye weed / gravel root is best historically known and most widely used. It was commonly used as a diuretic and to support urinary tract health, including the kidneys. The herb's name, "gravel root," is derived from its traditional use to help the body expel "gravel" or small kidney stones, and to relieve symptoms associated with kidney and bladder discomfort.

Historically, Native American and early European herbalists used gravel root as a diuretic and to purportedly "break down" or "expel" urinary stones. Its use was based on empirical observation rather than rigorous scientific study, and it was often prepared as a tea or tincture.

Clinical evidence: Despite its traditional reputation, there is little scientific evidence to support the efficacy of gravel root for kidney health. No well-designed clinical trials have evaluated its use for kidney support or the treatment of kidney stones. Most of the available information comes from historical texts, anecdotal reports, and herbalist literature.

There are very few, if any, well-controlled clinical studies evaluating gravel root's efficacy in treating or preventing kidney stones. Some laboratory studies have identified compounds such as euparin and other alkaloids that may have mild diuretic or anti-inflammatory effects.

Evidence strength: Traditional use only; no clinical evidence. The diuretic reputation is longstanding and cross-cultural, but it rests entirely on historical practice and anecdote. No clinical trials have been conducted.

4.3 Urinary Tract Infections

Gravel root was commonly employed as a remedy for urinary tract conditions, including infections, kidney stones, and other ailments of the urinary system. The herb was traditionally thought to help "flush out" the urinary tract and encourage urination, thereby assisting in the expulsion of pathogens or stones.

Clinical evidence: There is a significant lack of modern scientific evidence to substantiate gravel root's efficacy for urinary tract infections. Clinical trials and pharmacological studies examining its antibacterial or anti-inflammatory effects in the context of UTIs are virtually nonexistent. The main support for its use remains anecdotal or based on historical texts rather than rigorous scientific validation.

Evidence strength: No clinical evidence.

4.4 Fever and Diaphoretic Action

The earliest and most historically prominent use of joe-pye weed was as a febrifuge and diaphoretic. Joe Pye is said to have brewed decoctions of the plant bearing his name to induce sweating in typhus fever. The infusion was used to induce sweating and break a high fever. People have also used gravel root for fever from malaria, dengue virus, or typhus.

Evidence strength: Historical tradition only. No modern clinical evidence exists. The diaphoretic use is empirical, derived from colonial-era and indigenous practices.

4.5 Gout and Rheumatism

Gravel root has been used in gout and "rheumatism" — the latter a catch-all term used to describe conditions characterized by pain and stiffness in the muscles, joints, or surrounding fibrous tissue. Eclectic practitioners employed it in the treatment of chronic urinary disorders, hematuria, gout, and rheumatism.

Evidence strength: In vitro and limited animal evidence only. The anti-inflammatory activity of cistifolin in cell and animal models provides a plausible biological basis, but this has not been tested in human trials for gout or rheumatism specifically.

4.6 Other Traditional Applications

People have also used gravel root for arthritis-like pain and gout, as well as for fever from malaria, dengue virus, or typhus. Gravel root is also used to reduce stomach acid, increase urine flow, cause vomiting, and cause sweating, and as a stimulant and tonic. It has been used in cases of prostatitis, along with herbal analgesics and anti-inflammatories. Modern science has not confirmed efficacy for any of these applications.

5. Body Systems and Health Areas of Association

Based on traditional use and the limited preclinical research, joe-pye weed is associated with the following body systems:

• Urinary / Renal System: Primary traditional association — diuretic action, urinary gravel, kidney stone prevention or expulsion, cystitis, urethritis, prostatitis.
• Musculoskeletal / Immune System: Anti-inflammatory and antirheumatic use; gout; rheumatism. Supported at the preclinical level by cistifolin's integrin-inhibiting mechanism.
• Integumentary System: Topical poultice use on burns and wounds in indigenous practice.
• Febrile / Immune Response: Diaphoretic and antipyretic use; fever management in typhus and other febrile illness.
• Gastrointestinal System: Historical use as a stomach acid reducer, appetite stimulant, and general tonic.
• Respiratory System: Historical use for coughs (cough syrup formulations from flowers and leaves).

The interaction of gravel root with body systems, particularly the immune and urinary systems, is not fully understood.

6. Dosage Forms and Reported Dosages

There are no dosages established from controlled clinical trials. The following dosages are reported in traditional herbal and naturopathic literature:

• Tincture (fresh root, 1:4, 35% alcohol): 1–5 mL three times daily (TID).
• Tincture (dried root, 1:5, 25% alcohol): 1–5 mL three times daily (TID).
• Root decoction: 1 teaspoon per cup, 1 to 2 cups per day.
• Acute/fever use: One cup of the root decoction every 2 hours, or 5–15 drops of the tincture in a cup of water.
• Tincture (traditional dose): 5–15 drops in a cup of water.

These dosages derive from naturopathic and herbal practice references, not from controlled clinical trials, and should not be taken as validated therapeutic guidance. The British Herbal Pharmacopoeia (1991) is cited in the herbal literature as a reference monograph source for this plant.

7. Safety Considerations and Drug Interactions

Pyrrolizidine Alkaloids (PAs): The Primary Safety Concern

There is significant concern about using gravel root as medicine because it contains chemicals called hepatotoxic pyrrolizidine alkaloids (PAs). These chemicals may block blood flow in the veins and cause liver or lung damage. Gravel root preparations that are not certified and labeled "hepatotoxic PA-free" are considered likely unsafe.

There is a lot of concern about using gravel root as medicine because it contains chemicals called hepatotoxic pyrrolizidine alkaloids (PAs), which may block blood flow in the veins and cause liver damage. Hepatotoxic PAs might also cause cancer and birth defects.

Several Eupatorium species, including Eupatorium purpureum (gravel root), have hepatotoxic potential due to the presence of pyrrolizidine alkaloids. The American Herbal Products Association addressed this class of compounds: the AHPA recommended in 1996 that all products with botanical ingredients that contain toxic pyrrolizidine alkaloids bear a cautionary statement on the label, including "For external use only," "Do not apply to broken or abraded skin," and "Do not use when nursing."

It is likely unsafe to apply gravel root to broken skin. The dangerous chemicals in gravel root can be absorbed quickly through broken skin and can lead to dangerous body-wide toxicity.

This plant should not be used in large amounts or for a long time because it contains pyrrolizidine alkaloids. The PA content in this plant is considered to be in smaller quantities than in some other well-known plants such as comfrey, but the caution to avoid use in pregnancy still stands.

Adulteration Risk

It is important to ensure an authenticated source of this plant is obtained. There can be hybridization with other species or adulteration and contamination with other related species such as boneset (Eupatorium perfoliatum). The species hybridize widely in nature, making identification a challenge even for botanists. This is significant because the PA content may differ between species, and species misidentification is a documented quality-control problem in the herbal trade.

Pregnancy and Lactation

It is likely unsafe to use gravel root preparations that might contain hepatotoxic PAs during pregnancy. These products might cause birth defects and liver damage. It is also likely unsafe to use gravel root preparations that might contain hepatotoxic PAs if breastfeeding, as these chemicals can pass into breast milk and might harm the nursing infant. Its use is also contraindicated in pregnancy due to its abortifacient effect and during breastfeeding, again due to the pyrrolizidine alkaloids.

Liver Disease

Because of the pyrrolizidine alkaloids, internal use, particularly long-term use, may lead to hepatotoxicity and should be avoided in patients with liver disease.

Known Drug Interactions

Gravel root may have a diuretic effect. Taking gravel root might decrease how well the body eliminates lithium. This could increase lithium concentrations in the body and result in serious side effects. Lithium dosing may require adjustment.

Medications that cause the liver to break down gravel root (such as carbamazepine, phenobarbital, phenytoin, rifampin, and rifabutin) might enhance the toxic effects of chemicals contained in gravel root by accelerating the metabolic conversion of PA N-oxides into the active hepatotoxic parent alkaloids.

Overall Safety Summary

Gravel root is not a casual everyday herb. Modern human research is thin, product quality can vary, and there are meaningful safety questions around possible pyrrolizidine alkaloid exposure and adulteration with related plants. There is not enough reliable information to know if it is safe to take even "hepatotoxic PA-free" gravel root by mouth; it is best to avoid use.

8. Status in Official Herbal Compendia

Gravel root was listed in the U.S. Pharmacopoeia from 1820 to 1842. The British Herbal Pharmacopoeia (1991) is cited in the herbal research literature as a reference monograph source for this plant. No current European Medicines Agency (EMA) or WHO monograph specifically covering Eutrochium purpureum / gravel root was identified in sources consulted. Studies have shown that Eupatorium and its active principles possess a wide range of pharmacological activities, and an increasing amount of data supports application and exploitation for new drug development, but no approved pharmaceutical products based on this species were identified.

References

• Liu, Y. et al. (2015). "Chemical Constituents of Plants from the Genus Eupatorium (1904–2014)." Chemistry & Biodiversity. PubMed PMID 26460556.
• Habtemariam, S. (1998). "Cistifolin, an integrin-dependent cell adhesion blocker from the anti-rheumatic herbal drug, gravel root (rhizome of Eupatorium purpureum)." Planta Med. 64(8):683–5. PubMed PMID 10075543.
• Habtemariam, S. (2001). "Antiinflammatory activity of the antirheumatic herbal drug, gravel root (Eupatorium purpureum): further biological activities and constituents." Phytotherapy Research. 15(8):687–690.
• Roeder, E. (1983). "Pyrrolizidine alkaloids, flavonoids and volatile compounds in the genus Eupatorium." International Journal of Clinical Pharmacy. PubMed PMID 6364036.
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