Milkweed (Asclepias spp.): A Comprehensive Reference
1. Identity: Botanical Classification, Names, and Natural Source
Milkweed is the common name applied to plants of the genus Asclepias, a large group of perennial herbs in the family Apocynaceae (formerly placed in the separate family Asclepiadaceae). Common milkweed is a member of the Asclepiadaceae (milkweed) family and is one of about 115 species that occur in the Americas, with most species being tropical or arid land species. Of these, three species have the greatest relevance to human health and historical use:
- Asclepias syriaca L. — Common milkweed; the most widely distributed species in North America and the one most studied phytochemically. The species epithet syriaca refers to "of Syria," as Linnaeus mistakenly believed common milkweed originated in Syria. Other former scientific synonyms include Asclepias cornuti Decaisne, Asclepias intermedia Vail, and Asclepias kansana Vail. Other common names for this plant include Common Silkweed, Cotton Tree, Cottonweed, Milkplant, Monarch Flower, Pink Milkweed, Rosy Milkweed, Silkgrass, Silkweed, Silky Swallowwort, Swallowwort, Virginia Silk, and Virginia Silkweed.
- Asclepias tuberosa L. — Butterfly weed, also called pleurisy root; the species with the longest formal pharmaceutical history in North America. This brilliant-orange-flowered herb is native to and continues to grow primarily in the southwestern and midwestern United States; many plants similar to pleurisy root are known as milkweeds because they produce a milky sap—something pleurisy root does not do.
- Asclepias curassavica L. — Tropical or bloodflower milkweed; frequently studied for its cardenolide chemistry and potential anticancer properties.
The genus name Asclepias honors Asklepios, who was the ancient Greek god of medicine.
Geographic range: Asclepias syriaca is specifically common throughout the eastern half of North America. Common milkweed is found in fields and roadsides in all New England states.
Botanical description: Duration is perennial; habit is herbaceous. Leaves are elliptic, lanceolate, oblong, or ovate; inflorescence is an umbel; fruit type is a follicle. Plants typically reach 3–5 feet (90–150 cm) but can reach 8 feet (240 cm) in ditches and gardens. Slightly pendulous spherical umbels bear as many as 100 flowers per umbel, though usually 30 or more flowers. The characteristic follicle or pod contains many seeds, each with a tuft of silky white hairs that aids in wind-borne dispersion.
1.1 Common Forms and Preparations
Milkweed has been prepared and used in several distinct forms across its history:
- Dried root powder: The root was historically collected about the first of October, cut in transverse slices, dried in the shade, and, as soon as sufficiently dried, pulverized and bottled.
- Decoctions: Root decoctions prepared in water were a primary traditional preparation for internal use.
- Infusions (teas): A pleurisy root tea can be made by lightly simmering one teaspoon of the dried, chopped root in one pint of water for 10 to 15 minutes.
- Tinctures: Beyond its uses by indigenous people, milkweed was at one time a medicine that pharmacists prepared; milkweeds have been prepared as tinctures and used as emetics to induce vomiting in the case of poisoning.
- Topical latex (sap): The raw milky sap exuded from broken stems and leaves was applied directly to the skin. The latex from showy milkweed (A. speciosa) and common milkweed (A. syriaca) is used as a treatment for warts, ringworm, and other skin ailments.
- Food preparation: As a food, people ate the boiled young sprouts like asparagus, cooked the unopened floral bud clusters and firm green fruits, as well as the tender leaves and upper stalks. The flowers and buds often thickened soups. Dried buds were stored for winter use.
2. Traditional and Historical Use
2.1 Indigenous North American Use
Called Wah'tha or "raw medicine" by the Omaha nation, milkweed is well known to Native Americans as a cure for a variety of ailments, such as skin conditions, stomach ailments, chest pains, and the common cold.
Common milkweed (Asclepias syriaca) is used as a food by numerous North American Indigenous groups, yet also considered a poisonous plant by chemists and others; the details of traditional, indigenous preparation methods, which render it an edible and culturally important food choice, are reported in the ethnobotanical literature along with harvesting and tending methods.
Specific tribal uses are documented in ethnobotanical and USDA records. Native Americans used the young leaves and stems as well as the buds of A. syriaca as food. The Menominee ate the buds; the Ojibwa used the root as a female remedy; and the Potawatomi used the root for unspecified ailments. The Miwok people used the latex to remove warts, while the Cheyenne made a decoction of the dried plant tops and used it as an eyewash to heal snow blindness. Cherokee, Delaware, and Mohegan peoples used pleurisy root (Asclepias tuberosa) made into a cough remedy; today herbalists still use it for pleurisy, an inflammation in the lining around the lungs.
As a medicine, the plant supported treatment of venereal diseases, kidney and urinary dysfunction, rheumatism, and backaches. It was also used as a laxative, galactagogue, and contraceptive. Topically it was used to remove warts and treat bee stings, cuts, and ringworm.
Some Native Americans rubbed the latex juice on warts, moles, and ringworms; others drank an infusion of the rootstock to produce temporary sterility or as a laxative. One Mohawk antifertility concoction reportedly contained milkweed and Jack-in-the-pulpit, both considered dangerous and contraceptive.
The milky white sap was applied topically to remove warts, and the roots were chewed to cure dysentery. Infusions of the roots and leaves were taken to suppress coughs and used to treat typhoid fever and asthma.
2.2 European Settler and Early American Medical Use
Early European settlers called milkweed "pleurisy root" and used an infusion to relieve lung inflammation. The U.S. government listed the root of butterfly milkweed as an official herbal remedy from 1820 to 1936. More specifically, Asclepias tuberosa was listed in the United States Pharmacopeia from 1820 to 1905, and from 1906 to 1936 it was included in the National Formulary as an official botanical drug to treat the condition of pleurisy.
During the 1880s, A. syriaca was also listed in the U.S. Pharmacopeia. A tea made from the fresh or dried root was used as an alterative, an anodyne, an anthelmintic, a cathartic, a cicatrisant, a diaphoretic, a diuretic, an emetic, an expectorant, and a sedative. The tea was used to treat asthma, bronchitis, cancer, catarrh, dropsy, dyspepsia, kidney stones, pleurisy, rheumatism, scrofula, and typhoid.
An 1848 account in the Buffalo Medical Journal, reprinted in NLM Digital Collections, described the preparation and use of pleurisy root in detail. Pleurisy root was said to "equalize the circulation, produce copious expectoration and free diaphoresis, without inducing as much previous heat and excitement in the system as most other vegetable sudorifics." In the treatment of measles, this root was noted as often being of "essential service." The same source recorded a historical dosage: one ounce of the root boiled in three pints of water down to a quart, given in doses of half a gill every half hour; the dose of the powdered substance was recorded as ten to fifteen grains.
Uses for A. tuberosa appear in early American medical texts, including a mention in American Medical Botany, published in 1817–1820, in which author Jacob Bigelow wrote: "This fine vegetable is eminently entitled to the attention of physicians as an expectorant and diaphoretic."
2.3 Other Cultural Uses
Beyond its medicinal applications, milkweed served broader material purposes in indigenous and settler communities. The outer bark was used to make cord, thread, and bowstrings. The silky-haired tufts were used as stuffing for cushions, mattresses, pillows, and upholstery; they were also used as insulation, as a cotton substitute, and as thread. During World War II, milkweed floss was used in life jackets.
3. Key Constituents and Active Compounds
3.1 Cardenolides (Cardiac Glycosides)
The most pharmacologically and toxicologically significant compounds in milkweed are the cardenolides, a class of steroidal cardiac glycosides. These herbaceous perennials produce a milky sap that is variably toxic across the more than 140 species; the healing properties of the plant are attributed to the sap, rich in secondary metabolites such as latex (isoprene polymers), cardenolides (steroid derivatives), and alkaloids.
In the genus Asclepias, cardenolides in milkweed plants have an established role in plant–herbivore and predator–prey interactions, based on their ability to inhibit the membrane-bound Na+/K+-ATPase enzyme. This enzyme inhibition is the primary mechanism by which the compounds exert both their toxic and potential therapeutic effects.
The level of toxicity varies dramatically among species and plant parts. Not all milkweeds have identical toxicity—species like Asclepias curassavica often have higher cardenolide concentrations than A. tuberosa.
Specific cardenolides isolated and characterized from Asclepias species include afroside, asclepin, asclepiadin, calactin, calotropin, gomphoside, syriogenin, syrioside, uscharidin, uscharin, uzarigenin, frugoside, and gofruside, among others. In Asclepias tuberosa, the cardiac glycosides identified include cardenolide-type compounds: afroside, asclepin, asclepiadin, calactin, calotropin, gomphoside, syriogenin, syrioside, uscharidin, uscharin, and uzarigenin.
Phytochemical investigation of the dried biomass of Asclepias syriaca has identified five new compounds along with 19 known structures. The secondary metabolites isolated and identified from this plant showed wide structural diversity including pentacyclic triterpenes, cardiac glycosides, flavonoid glycosides, lignans, a phenylethanoid, and a glycosylated megastigmane.
3.2 Flavonoids and Polyphenols
Flavonoids identified in Asclepias tuberosa include kaempferol, quercetin, rutin, and isorhamnetin. Plants in the Asclepiadaceae family are rich in phytochemical constituents such as alkaloids, flavonoids, terpenoids, phenolic compounds, glycosides, and saponins, and these constituents have been found to exhibit a range of pharmacological activities.
3.3 Pregnane Glycosides
From the roots of Asclepias incarnata L., researchers obtained twenty-nine new oxypregnane glycosides along with two known cardenolides, frugoside and gofruside, and three known 12-O-acylated pregnane glycosides. Their structures were determined to be tri- to penta-glycosides of isolineolon, 12-O-acetyllineolon, ikemagenin, 12-O-benzoylisolineolon, and two new 12-O-acylated pregnanes.
Pregnane glycosides from the root of A. tuberosa have been reported to stimulate human fibroblasts to proliferate, which could have an anti-aging effect on skin (Warashina et al., 2011). Pregnane glycosides from a number of genera of milkweeds including Asclepias were found to suppress steroidogenesis in human adenocarcinoma cells (Komarnytsky et al., 2013).
3.4 Resinoids and Alkaloids
The root of A. tuberosa contains compounds such as resins, glycosides, and flavonoids that have been associated with expectorant and anti-inflammatory properties. Milkweed sap (latex) also contains alkaloids and proteolytic enzymes that can irritate skin and mucous membranes.
3.5 Galitoxin (Neurotoxin)
Galitoxin, a toxic principle, is found in all vegetative parts of some milkweed species. Cardiac glycosides are found in the majority of milkweed species, while a neurotoxin is specific to the whorled-leaf types; of the two, the neurotoxin is the most lethal.
3.6 Mechanisms of Action
The primary established mechanism for the cardenolides is inhibition of the Na+/K+-ATPase pump in cellular membranes. Milkweeds contain various toxic cardenolides (cardiac glycosides) that have cardiotoxic effects; the cardenolides act by inhibiting Na+-K+-ATPase, thereby affecting myocardial conduction and contractility.
Cardiac glycosides disrupt proper muscle (including the heart) and kidney function, the nervous system, and the body's acid-base balance.
In addition to the cardiotoxic effects of the cardenolides common to most milkweeds, other glycosides and resinoids identified in milkweeds have direct effects on the respiratory, digestive, and nervous systems, causing dyspnea, colic and diarrhea, muscle tremors, seizures, and head pressing.
In the context of potential therapeutic use, the lactone ring structure of cardenolides plays a central role. The lactone ring at C17β has been considered to be responsible for inotropic activity, bringing about conformational changes on the enzyme that give rise to its inhibition; indeed, that is the most differentiating feature from steroid hormones.
4. Scientific Evidence by Area of Use
4.1 Respiratory Conditions (Pleurisy, Bronchitis, Asthma)
Respiratory disease — particularly pleurisy and bronchitis — represents the area for which milkweed (A. tuberosa especially) accumulated the most formal historical and pharmacopeial recognition.
Traditional claims: European Americans used Asclepias tuberosa, called "pleurisy root," to relieve inflammation of the lining of the lungs and thorax, and to relieve bronchial and pulmonary trouble. Pleurisy root was described as a stimulant to the vagus nerve, producing perspiration, expectoration, and bronchial dilation, useful for pleurisy and mild pulmonary edema, increasing fluid circulation, cilia function, and lymphatic drainage.
Scientific evidence: Pleurisy root health benefits are often described in herbal references, but there are no human clinical studies showing that Asclepias tuberosa treats pleurisy, pneumonia, bronchitis, coughs, or any other medical condition. Insufficient work has been done to identify the active constituents in pleurisy root or its medicinal actions; no human studies have been conducted to determine whether it is effective for any indication.
Evidence strength assessment: No clinical evidence. Support for respiratory use is entirely historical and anecdotal. In the past, pleurisy was used for pulmonary conditions such as asthma and bronchitis; however, there is insufficient evidence currently available in humans to support the use of pleurisy for any indication.
4.2 Anticancer / Cytotoxic Activity
Research into the cytotoxic potential of Asclepias compounds has been conducted in vitro and in animal models, primarily driven by the known Na+/K+-ATPase inhibitory activity of cardenolides.
The secondary metabolites isolated and identified from A. syriaca include pentacyclic triterpenes, cardiac glycosides, flavonoid glycosides, lignans, a phenylethanoid, and a glycosylated megastigmane. Several isolates were tested against the cancer breast cell line Hs578T, and those showing IC50 values lower than 50 µM were further investigated in three additional breast cancer cell lines (MCF-7, T47D, and Sk-Br-3) and the normal breast cell line Hs578Bst.
For A. curassavica, a PMC-indexed study examined the antitumor activity of an ethyl acetate extract. The ethyl acetate extract of Asclepias curassavica (EAAC) exhibited the highest cytotoxic activity in vitro; EAAC could inhibit sensitive cell line NIC-H1975 proliferation in a concentration-dependent and time-dependent manner; EAAC had a significant inhibitory effect on NIC-H1975 tumor growth in BALB/c-nu/nu mouse; and NIC-H1975 cells showed obvious apoptosis characteristics after EAAC treatment. The proposed mechanism involved induction of the apoptotic pathway: Fas, caspase family members caspase-3, caspase-9, and caspase-8 showed dose-dependent induction by EAAC treatment, with increasing PARP cleavage; additionally, EAAC significantly downregulated antiapoptotic proteins Bcl-2, XIAP, survivin, and Mcl-1 and upregulated proapoptosis proteins Bak, Bax, as well as activation of p38 and JNK MAPK signaling pathways.
An earlier study on A. curassavica isolated and characterized a new cardenolide alongside numerous known cardenolide glycosides, and all isolates were evaluated for their cytotoxic activity against HepG2 and Raji cell lines.
Evidence strength assessment: Preclinical only (in vitro and animal models). All anticancer evidence to date derives from cell-culture studies and murine xenograft experiments. No human clinical trials of milkweed extracts or isolated cardenolides for cancer treatment have been reported in the peer-reviewed literature. These findings establish a pharmacological rationale for further investigation but cannot be extrapolated to clinical efficacy or safety in humans.
4.3 Skin Conditions (Warts, Ringworm, Topical Applications)
The latex from showy milkweed (A. speciosa) and common milkweed (A. syriaca) is used as a treatment for warts, ringworm, and other skin ailments. The milky sap has also been applied for treating insect stings, moles, ringworms, and warts.
Pregnane glycosides from the root of A. tuberosa have been reported to stimulate human fibroblasts to proliferate, which could have an anti-aging effect on skin (Warashina et al., 2011).
Evidence strength assessment: Traditional use with very limited laboratory support; no controlled human trials. The use of milkweed latex for wart removal is one of the most widely documented traditional applications, but there are no peer-reviewed randomized trials validating efficacy or comparing it to standard treatments.
4.4 Antimicrobial Activity
A range of bioactivities has been found in Asclepias native plants including antioxidant, antitumor, anti-inflammatory, antimicrobial, and antiviral activity. Plants in the Asclepiadaceae family have demonstrated antimicrobial properties, providing a defense against various microorganisms.
Evidence strength assessment: Preliminary; largely in vitro. Antimicrobial activity has been identified in laboratory assays of various Asclepias extracts, attributed in part to the flavonoid and cardenolide content. No human clinical trials specifically testing milkweed for infection treatment are documented in the available literature.
4.5 Antioxidant Activity
A polyphenolic preparation, separated and purified from an alkaline extract of A. syriaca leaves, was assessed for oncostatic action in rats (Rotinberg et al., 2000). Plants in the Asclepiadaceae family have antioxidant properties, which help protect cells from damage by harmful free radicals.
Evidence strength assessment: Preliminary; largely in vitro or animal-based. No controlled human trials have evaluated the antioxidant effects of milkweed preparations as dietary supplements.
4.6 Fertility / Contraceptive Effects
Pregnane glycosides from a number of genera of milkweeds including Asclepias were found to suppress steroidogenesis in human adenocarcinoma cells (Komarnytsky et al., 2013). Historical records document the use of milkweed by Native American groups to affect reproductive function, and laboratory research has identified relevant steroidogenic pathways. One Mohawk antifertility concoction contained milkweed and Jack-in-the-pulpit, both considered dangerous and contraceptive.
Evidence strength assessment: Traditional ethnobotanical use; some preliminary laboratory mechanistic data. No human clinical evidence supports or quantifies contraceptive effects from milkweed preparations.
4.7 Gastrointestinal / Laxative / Diuretic Effects
A tea made from the fresh or dried root was historically described as functioning as a cathartic, diuretic, and emetic. A leaf infusion was used for treating stomach ailments.
Evidence strength assessment: Traditional use only; no controlled clinical evidence.
5. Body Systems and Health Areas Associated with Milkweed
Based on the combination of traditional use, historical pharmacopeial records, and available laboratory evidence, milkweed has been associated with the following body systems:
- Cardiovascular system: Contains cardenolides that directly inhibit Na+/K+-ATPase in cardiac muscle. The plant contains cardiac glycosides, allied to digitalins used in treating some heart disease.
- Respiratory system: Historically the primary therapeutic target. Root tea was used to treat asthma, bronchitis, and pleurisy.
- Integumentary system (skin): Direct topical applications of latex for warts, ringworm, cuts, and bee stings are among the oldest recorded uses.
- Urinary / renal system: Root preparations were recorded as having diuretic properties.
- Musculoskeletal system: The plant was associated with treatment of rheumatism and backaches.
- Gastrointestinal system: Preparations described as cathartic, emetic, and used in dyspepsia.
- Reproductive system: Documented use as a galactagogue and antifertility agent in ethnobotanical records.
- Oncology (experimental): In vitro and animal research suggests cytotoxic properties against multiple cancer cell lines, attributed primarily to cardenolide constituents.
6. Dosage Forms and Reported Dosages
No standardized dosages have been established through clinical trials. Dosages reported in historical sources and in the pre-pharmacopeial and pharmacopeial literature include the following:
- Powdered root (historical): One ounce of the root boiled in three pints of water down to a quart, given in doses of half a gill every half hour; the dose of the powdered substance was recorded as ten to fifteen grains.
- Infusion/tea: A pleurisy root tea can be made by lightly simmering one teaspoon of the dried, chopped root in one pint of water for 10 to 15 minutes.
- Formal evidence note: Insufficient work has been done to identify the active constituents in pleurisy root or its medicinal actions; no human studies have been conducted to determine whether it is effective for any indication. This means that no dose has been validated for safety or efficacy in a clinical setting.
7. Safety Considerations and Drug Interactions
7.1 Intrinsic Toxicity
Milkweeds (genus Asclepias and close relatives) contain toxic compounds, especially cardiac glycosides (cardenolides), and can be poisonous if eaten or mishandled. Milkweed contains cardenolides concentrated in the milky latex; symptoms from ingestion usually begin with gastrointestinal upset, and large ingestions can affect the heart and nervous system.
The milky white sap contains high concentrations of steroid derivatives called cardenolides; these compounds are present both in live plants and in dried milkweed (which can sometimes be found in baled hay or in pastures after a plant is cut or dies). Cardiac glycosides disrupt proper muscle (including the heart) and kidney function, the nervous system, and the body's acid-base balance.
7.2 Human Poisoning Cases
Documented cases of human poisoning from milkweed exist in the peer-reviewed literature. A published case report in Military Medicine (Oxford Academic) described: Asclepias syriaca, or common milkweed, is a potentially edible plant that also contains cardioactive steroids akin to digoxin. A 38-year-old female amateur forager boiled and sautéed 8–10 milkweed pods before ingesting them; she developed vomiting and heart palpitations within 1 hour and presented to an emergency department 3 hours after ingestion.
The same publication noted that preparation by cooking does not fully eliminate risk: traditional cooking procedures of the Native American Myaamia people included repeated boiling with fresh water, which may reduce the concentration of cardiac glycosides in common milkweed by half. Repeated boiling prior to consumption may decrease the concentration of cardioactive steroids, but should not be assumed to eliminate the risk of poisoning after ingestion, as "even a modest serving of 10 g of cooked plant material [could] contain 1 mg of digitoxin-equivalent cardiac glycoside."
A lethal dose of approximately 2% of the total body weight of fresh plant material has been estimated for some species.
7.3 Livestock Toxicity
All milkweeds are poisonous to some degree to all classes of livestock, including poultry. Horses, cattle, and sheep are all susceptible; a dosage of Whorled Milkweed of 0.1%–0.5% body weight of the animal is fatal. Cardiac signs include bradycardia or tachycardia, hypotension, and arrhythmia. Histological lesions and myocarditis are common. While the fresh, green plant material is the most toxic, dried plants present in pastures or hay retain their toxicity.
7.4 Dermal and Ocular Irritation
Milkweed contains compounds that can be toxic if consumed in large amounts; its milky sap can also irritate skin and eyes in some people.
7.5 Drug Interactions
Pleurisy root should be avoided with heart medications because plants in the Asclepias genus contain cardiac glycosides; its interaction list specifically includes digoxin and several beta-blockers and calcium-channel blockers.
Some natural medicine textbooks note that pleurisy root contains large amounts of cardiac glycosides; therefore, large doses should be avoided and pleurisy root should be used cautiously in patients with cardiovascular conditions or taking cardiac glycosides.
7.6 Pregnancy and Lactation
Pleurisy root is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence. The pleurisy root is not to be taken by women who are pregnant, as this plant can act like the hormone estrogen; it also contains a chemical that can lead to heart problems, or cause complications with individuals taking heart medications.
7.7 Species-Specific Toxicity Variation
Milkweeds are most toxic during rapid growth and retain their toxicity even when dried in hay. Toxicity varies with the species and growing conditions; however all milkweeds should be considered potentially poisonous, especially the narrow-leafed species. Some broad-leafed species that contain high levels of cardenolides include Asclepias asperula, A. labriformis, A. eriocarpa, and A. curassavica.
Two clinical manifestations of poisoning have been reported: (1) a digestive tract/cardiac type, and (2) a neurological type; the cardiotoxic effect is often lethal.
8. Summary of Evidence Quality
Milkweed occupies an interesting position in the history of North American medicine: it was among the continent's most widely used indigenous remedies, achieved formal pharmacopeial recognition for over a century, yet has never been the subject of rigorous human clinical trials for any indication. The following summarizes the evidence quality by domain:
- Traditional / historical use: Extensively documented across dozens of Native American nations and in 19th-century Euro-American medical texts. Rich and consistent record of respiratory, dermatological, genitourinary, and gastrointestinal applications.
- Phytochemistry: Well-characterized. The cardenolide, flavonoid, pregnane glycoside, and phenolic profiles have been studied in multiple peer-reviewed publications.
- Mechanism of action: The Na+/K+-ATPase inhibitory mechanism of cardenolides is firmly established in pharmacology. Apoptosis-inducing signaling pathways (Bcl-2 family, caspase cascade, MAPK) have been documented in cell-culture studies.
- Human clinical evidence: Absent for all indications. In the past, pleurisy was used for pulmonary conditions such as asthma and bronchitis; however, there is insufficient evidence currently available in humans to support the use of pleurisy for any indication.
- Preclinical (anticancer) evidence: Promising in vitro cytotoxicity data for multiple cancer lines, and some in vivo (murine) evidence, but no translation to human trials to date.
- Safety evidence: Strongest domain. The cardiac toxicity of cardenolides is well-documented in animals and in documented human poisoning cases, and the interaction risk with cardiac drugs (especially digoxin) is pharmacologically coherent and supported in clinical reference databases.
References
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