Euphorbia milii (Euphorbiaceae) Crown of Thorns, Christ Thorn

Euphorbia milii is a medicinally significant succulent shrub with a long history of use in traditional medicine, now supported by a growing body of modern scientific research. It has a potent and diverse phytochemical profile, dominated by 74 unique diterpenoids, which contribute to a wide spectrum of pharmacological activities including anti-inflammatory, analgesic, antimicrobial, anticancer, antioxidant, and antidiabetic effects. The plant has demonstrated significant efficacy in treating inflammatory conditions, with recent research highlighting its antiadipogenic and anti-psoriatic potential. However, a critical caution is warranted: the plant's milky latex is highly toxic and a severe irritant, requiring extreme care in handling and use. Significant research gaps exist in human clinical trials and pharmacokinetic studies. The plant holds high commercial potential as a source of novel pharmaceutical compounds, particularly for inflammation, metabolic disorders, and infectious diseases.

1. Taxonomic Insights

Species: Euphorbia milii Des Moul.

Family: Euphorbiaceae (Spurge Family)

Genus: Euphorbia

Basionym: Euphorbia milii Des Moul.

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Botanical Description

Euphorbia milii is a slow-growing, succulent, woody shrub that can reach up to 1.8 metres in height, exhibiting a variable, scandent (climbing) growth habit. The stems are cylindrical (terete), 0.5 to 1 centimetre in diameter, branching, and densely covered with sharp, greyish to brown spines arranged in spirals or rows. The spines can be solitary or in groups, reaching 1 to 3 centimetres in length. The leaves are deciduous, fleshy, and typically clustered on new growth. They are obovate to oblong-spatulate, measuring 1.5 to 5 centimetres in length and 0.8 to 2 centimetres in width.

Key Identification Features:

The plant's most distinctive feature is its inflorescence. It produces several cyathia (the unique cup-like flower structure of the Euphorbia genus) in long-peduncled, dichotomous cymes. Each cyathium is subtended by a pair of showy, petal-like bracts (cyathophylls) that are broadly ovate, 8 to 12 millimetres long, and can be red, pink, yellow, or white. The true flowers are small and inconspicuous. The fruit is a small capsule (rarely seen in cultivation). It is native to Madagascar and is now widely cultivated as an ornamental throughout the tropics and subtropics. It is a common houseplant in temperate regions.

Distribution: Native to Madagascar. Widely cultivated globally in tropical, subtropical, and temperate regions. In China, it is commonly grown as an ornamental. In Thailand, many cultivated forms are hybrids with E. lophogona.

Conservation Status: The plant is classified as Least Concern (LC) by the IUCN.

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Etymology

The generic name Euphorbia is derived from Euphorbus, the Greek physician to King Juba II of Numidia (c. 50 BC to 19 AD), who was the first to use a succulent euphorbia for medicinal purposes. The specific epithet milii commemorates Baron Milius, the Governor of Réunion, who introduced the species to France in 1821. The common name, "Crown of Thorns," comes from a legend associating the plant's spiny stems with the crown worn by Christ at his crucifixion.

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2. Common Names

Scientific Name: Euphorbia milii | English: Crown of Thorns, Christ Plant, Christ Thorn | Chinese: 鐵海棠 (Tie Hai Tang) | Thai: โป๊ยเซียน (Poi Sian), ว่านมุงเมือง (Wan Mung Mueang), พระเจ้ารอบโลก (Phra Chao Rop Lok) | Hindi: Not found in traditional listings.

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3. Related Herbs from the Euphorbiaceae Family

Euphorbia hirta (Asthma-weed): Used traditionally for respiratory ailments, skin conditions, and intestinal parasites. It is known for its anti-inflammatory and antimicrobial properties.

Euphorbia lactea (Mottled Spurge): An ornamental cactus-like plant. Its latex is used traditionally for treating warts and skin ailments, but is also highly toxic and a skin irritant.

Ricinus communis (Castor Oil Plant): The source of castor oil, used as a purgative and for various skin conditions. Its seeds contain the highly toxic protein ricin.

Jatropha curcas (Physic Nut): Used in traditional medicine for its purgative and wound-healing properties. Its seeds are a source of a toxic oil.

Manihot esculenta (Cassava): A major food crop, but the raw plant contains cyanogenic glucosides that release toxic hydrogen cyanide if not properly processed. This highlights the toxic potential common within the Euphorbiaceae family.

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4. Medicinal Uses: Summary of Primary and Secondary Actions

Primary Actions:

Anti-inflammatory: The plant demonstrates significant anti-inflammatory activity, supporting its traditional use for inflammatory conditions. Key compounds include various diterpenoids. Research on an imiquimod-induced psoriasis-like mouse model showed that topical application of E. milii fractions significantly reduced inflammation, validating its traditional use for skin ailments.

Analgesic (Pain Relief): Traditional use for pain relief is supported by the presence of analgesic diterpenoids.

Antimicrobial: The plant exhibits broad-spectrum antimicrobial activity against various bacteria (including Klebsiella pneumoniae, Staphylococcus epidermidis) and fungi (including Candida albicans). The latex and various solvent extracts have been effective in laboratory tests.

Antioxidant: The plant shows potent free radical scavenging activity, attributed to its phenolic compounds and flavonoids.

Anticancer: The methanolic extract of the leaves has demonstrated significant antiproliferative activity against A375 human melanoma cell lines, with an IC50 of 199.45 µg/mL, compared to the standard drug Cisplatin. Other research has also confirmed its cytotoxic and antiproliferative potential.

Antidiabetic: The methanolic leaf extract has shown potent inhibition of the enzyme alpha-amylase (IC50 of 171.28 µg/mL), suggesting a potential to slow carbohydrate digestion and manage postprandial blood glucose levels. Research has also identified a stigmasterol derivative from the aerial parts with antidiabetic activity via in silico docking studies.

Molluscicide: A key and well-documented activity. The latex and extracts are highly effective in controlling snail populations, particularly Biomphalaria glabrata, the vector of schistosomiasis (a parasitic disease).

Secondary Actions:

Anthelmintic: Used traditionally for intestinal parasites, with scientific support from in vitro studies on parasitic worms.

Anti-gout: Traditional use for managing gout is supported by research on its anti-inflammatory and uric acid-lowering potential.

Antiviral: Preliminary research suggests potential activity against viruses, including Epstein-Barr Virus.

Antiadipogenic: Recent research has isolated five new ent-rosane diterpenoids (Euphomillanols A-E) that showed potent antiadipogenic effects in 3T3-L1 adipocyte cells, suggesting a potential role in managing obesity and related metabolic disorders. The most potent compound had an EC50 of 3.92 µmol/L.

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Medicinal Parts

The stems, leaves, roots, and latex (sap) are all used medicinally, though with extreme caution due to toxicity. The use of the latex is particularly hazardous.

Stems: The primary part used in Traditional Chinese Medicine (TCM). Used to disperse abscesses, remove toxins, resolve phlegm, expel pus, and promote diuresis. The recommended dose in TCM is 9 to 15 grams.

Leaves: Also used in TCM for similar purposes as the stems. The methanolic extract of the leaves is the focus of much modern pharmacological research for its anticancer, antidiabetic, and antioxidant activities.

Roots: Used in TCM to activate blood circulation.

Latex (Sap): The most potent and most dangerous part. Used externally in very small amounts to treat warts, boils, and skin ulcers. It is also the source of the potent molluscicidal compounds.

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5. Phytochemistry

5.1 Diterpenoids: The Major Constituents

To date, 85 compounds have been identified from E. milii, with diterpenoids being the most abundant and significant class, comprising 74 of the total compounds (87.06%). These diterpenoids are primarily responsible for the plant's diverse pharmacological activities. They include several structural types, with recent discoveries highlighting novel ent-rosane diterpenoids:

ent-Rosane Diterpenoids (ent-RDs): A 2024 study isolated five new, highly oxygenated ent-rosane diterpenoids, named Euphomillanols A-E, from the plant. Compounds 1 and 2 were found to have an unprecedented 7/7/6-fused tricyclic ring system, which is a significant finding in natural product chemistry. All five compounds exhibited antiadipogenic activity.

Other Diterpenoids: A 2024 study on an imiquimod-induced psoriasis model identified several known diterpenoids, including 17-hydroxyjatropholone, euphorol, miliol, and euphomilones A-C, among others.

5.2 Triterpenoids and Steroids

The plant contains 6 triterpenoids (7.06%) and 2 steroids (2.35%). Phytochemical screening has detected steroids and phytosterols. A stigmasterol derivative, stigmasta-5,22-dien-3β-ol, has been identified in the aerial parts and is linked to antidiabetic potential.

5.3 Flavonoids and Phenolic Compounds

The plant is a source of flavonoids, with 2 identified so far (2.35%). Phytochemical screening has confirmed the presence of flavonoids, phenols, and tannins, which contribute to its antioxidant and antimicrobial activities. One specific flavonoid, 3,3',4',5,7-pentahydroxyflavone, has been isolated and is being studied for its bioactivity.

5.4 Other Compounds

Cardiac Glycosides: Detected during phytochemical screening.

Saponins: Detected in phytochemical analysis.

Alkaloids: Detected in phytochemical analysis.

Macrocyclic Lactone: One compound (1.18%) has been identified from this class.

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6. Mechanisms of Action

6.1 Anti-inflammatory Activity: Potential Psoriasis Management

The anti-inflammatory effects are largely attributed to the diterpenoid content. A key study on the anti-psoriatic potential of E. milii provided strong evidence of its mechanism: In an imiquimod-induced psoriasis-like mouse model, topical application of the petroleum ether and ethyl acetate fractions significantly reduced the expression of pro-inflammatory cytokines IL-17, IL-22, and IL-23. It also modulated the expression of key inflammatory markers, demonstrating a pathway similar to conventional anti-inflammatory agents.

6.2 Antiadipogenic Activity: Obesity Management

The recently discovered Euphomillanols A-E (ent-rosane diterpenoids) exhibited potent antiadipogenic effects in 3T3-L1 adipocytes. This suggests a mechanism where these compounds inhibit the differentiation of pre-adipocytes into mature fat cells, potentially offering a natural approach to managing obesity and related metabolic disorders.

6.3 Anticancer Activity: Cell Proliferation Inhibition

The methanolic extract of the leaves demonstrates anticancer activity against A375 human melanoma cell lines. The mechanism appears to be through the inhibition of cell proliferation, as shown by the MTT assay with an IC50 of 199.45 µg/mL. This activity is attributed to the rich phytochemical composition of the extract, including flavonoids, phenols, and steroids.

6.4 Antioxidant Activity

The plant's significant antioxidant activity is driven by its phenolic and flavonoid content. These compounds act as potent free radical scavengers, protecting cells from oxidative stress and damage, which is a central mechanism in many of the plant's therapeutic benefits.

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7. Traditional and Ethnobotanical Uses

7.1 Skin Conditions and Inflammation (Abscesses, Boils)

Formulation: Whole plant (stems and leaves), or latex (with extreme caution). Used externally.

Preparation and Use: A decoction of the stems is used for treating carbuncles, abscesses, and other inflammatory skin conditions. The latex, applied sparingly and very carefully, is used to treat boils, warts, and skin ulcers.

Scientific Validation: The anti-inflammatory, antimicrobial, and anti-psoriatic activities identified in modern research strongly support the traditional use for a range of skin conditions.

7.2 Schistosomiasis Vector Control

Formulation: Latex.

Preparation and Use: The latex is a potent molluscicide. It is used in water bodies to control populations of snails that act as intermediate hosts for the parasite that causes schistosomiasis (bilharzia).

Scientific Validation: This is one of the best-documented and scientifically validated traditional uses of E. milii. The latex's molluscicidal activity has been studied extensively. It is considered a promising and potentially affordable alternative to synthetic chemical molluscicides for use in schistosomiasis control programs.

7.3 Hepatitis and Oedema

Formulation: Whole plant decoction.

Preparation and Use: In Traditional Chinese Medicine (TCM), the plant is used internally to treat hepatitis, severe abdominal oedema, and to promote diuresis. The recommended dose of the stems, leaves, or roots is 9–15 grams.

Scientific Validation: The plant's anti-inflammatory, hepatoprotective, and diuretic properties provide a pharmacological basis for these uses, though more research is needed to fully validate the hepatoprotective effects.

7.4 Regional Ethnomedicinal Applications Summary

China (TCM): Used to treat carbuncles, abscesses, hepatitis, oedema, and to promote pus drainage and detoxification. It is also used to activate blood circulation (roots).

Pakistan: Used for various infectious diseases, which aligns with its identified antimicrobial activity.

International Folk Medicine: The latex is used for warts and skin ulcers. An infusion of the plant is used for pain relief and to treat intestinal worms, respiratory infections, snake and scorpion bites, and body pains. In some contexts, the plant is used for its anti-inflammatory and analgesic properties for rheumatism.

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8. Healing Recipes, Teas, Decoctions, and Preparations

⚠️ CRITICAL WARNING: TOXICITY

Do not attempt to prepare or use any part of this plant internally. The following information is for educational purposes only. The milky sap (latex) is extremely irritating and toxic. Contact with skin can cause severe dermatitis, and contact with eyes can cause keratouveitis and temporary blindness. Ingestion can cause severe gastrointestinal distress.

8.1 Traditional External Use for Skin Conditions (Highly Cautionary)

Purpose: To treat warts, boils, and skin ulcers (as per traditional reports).

Preparation and Use: This is the most hazardous method. The latex is applied sparingly to the affected area using a cotton swab, ensuring it does not touch healthy skin. This should only be considered under the strict guidance of a trained healthcare professional. It is not recommended for home use.

Scientific Validation: The plant's antimicrobial and anti-inflammatory properties provide a scientific basis for its use in treating skin infections, but the risk of toxicity is very high.

8.2 Traditional TCM Decoction (For Educational Reference Only)

Purpose: As per TCM classics, it is used to treat abscesses, hepatitis, and oedema.

Preparation and Use: A decoction is made by boiling 9 to 15 grams of the dried stems, leaves, or roots in water. This is a traditional method, but it is essential to reiterate that internal use is extremely dangerous due to the plant's toxicity. This information is provided only for its historical and academic context.

Scientific Validation: The anti-inflammatory and analgesic properties of the plant's diterpenoids offer some scientific rationale for its use, but the risks associated with its use are severe and outweigh the benefits in all but the most controlled clinical settings.

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9. Clinical Significance and Evidence Summary

9.1 Evidence Hierarchy by Activity

Anti-inflammatory: Strong preclinical evidence. A 2024 study on an imiquimod-induced psoriasis-like mouse model showed significant reduction in inflammatory markers. Other in vitro and in vivo studies also confirm this activity.

Antiadipogenic: Strong preclinical evidence. A 2024 study isolated five new compounds with an EC50 of 3.92 µmol/L. This is a new and highly promising area of research.

Molluscicide: Strong preclinical evidence. The latex has been shown to be an effective molluscicide in numerous studies, with a focus on controlling schistosomiasis vectors.

Anticancer: Moderate preclinical evidence. A 2024 study showed significant inhibition of A375 melanoma cells (IC50 199.45 µg/mL). Other research confirms cytotoxic potential.

Antidiabetic: Moderate preclinical evidence. A 2024 study showed potent α-amylase inhibition (IC50 171.28 µg/mL). Other research supports this activity.

Antimicrobial: Moderate preclinical evidence. The plant shows activity against K. pneumoniae, S. epidermidis, and C. albicans.

Analgesic: Moderate preclinical evidence. The plant is used traditionally for pain relief, and its diterpenoids are reported to have analgesic activity.

Antioxidant: Moderate preclinical evidence. The plant exhibits good radical scavenging activity.

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10. Safety and Toxicology

10.1 Toxicity Profile

CRITICAL WARNING: This plant is highly toxic.

Toxic Part: The milky latex (sap) is the poisonous part.

Toxic Constituents: The sap contains milliamines, euphorbol, and euphorbin, which are strong irritants.

Mechanism: These compounds cause severe irritation and inflammation of the skin and mucous membranes. They are also known to be tumor-promoting diterpene esters.

10.2 Poisoning Features

Skin Contact: Irritant contact dermatitis, blistering, and swelling.

Eye Contact: Severe pain, lacrimation (tearing), corneal abrasion, keratoconjunctivitis, blurred vision, and even temporary blindness. A case report documented a 64-year-old man who developed keratouveitis (inflammation of the cornea and uvea) after accidental contact with the sap. While the condition resolved with treatment, it required steroidal eye drops and recovery took three weeks.

Ingestion: Swelling of the oral mucosa, nausea, vomiting, diarrhoea.

10.3 Contraindications and Precautions

Pregnancy and Lactation: Insufficient safety data exists. Pregnant or nursing women should avoid all contact due to toxicity.

Known Hypersensitivity: Individuals with known hypersensitivity to Euphorbia species should avoid use.

10.4 Potential Drug Interactions

Drug interactions have not been formally studied for E. milii. However, due to its potent pharmacological activities, there is a potential for interactions.

Antidiabetic Medications: The plant's alpha-amylase inhibitory activity suggests it could have an additive effect with other antidiabetic drugs, potentially leading to hypoglycaemia.

Anticancer and Immunomodulatory Medications: Due to its cytotoxic and immunomodulatory potential, caution is warranted when combined with other potent medications.

10.5 First Aid & Clinical Management

Skin Contact: Immediately wash the affected area thoroughly with soap and water.

Eye Contact: Immediately and continuously flush the eye with copious amounts of water for at least 15 minutes. Seek immediate medical attention.

Ingestion: Do not induce vomiting. Rinse the mouth and seek immediate medical attention.

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11. Quality Control Parameters

11.1 Marker Compounds for Standardisation

Key compounds suitable as quality markers include the five recently discovered Euphomillanols A-E (for antiadipogenic activity), and other known diterpenoids such as euphorol and miliol (for anti-inflammatory activity). The specific diterpenoid profile is crucial for standardisation due to the high percentage of these compounds (87.06%) in the phytochemical profile.

11.2 Recommended Analytical Methods

High-performance liquid chromatography (HPLC) with diode array detection (DAD) or liquid chromatography with tandem mass spectrometry (LC-MS/MS) is recommended for the quantification and identification of the unique diterpenoid markers. X-ray crystallography and spectroscopic methods (such as NMR and ECD) are used for determining the structures of novel compounds.

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12. Cultivation and Sustainability

12.1 Growth Requirements

Climate: The plant thrives in tropical and subtropical climates but is widely grown as a houseplant in temperate regions.

Habitat: It prefers well-drained soil and can tolerate dry conditions.

Soil: It prefers a well-drained, sandy or rocky substrate, typical of a succulent plant.

Propagation: It is easily propagated from stem cuttings, which must be allowed to dry and callus over before planting to prevent rot.

12.2 Sustainable Harvesting

Plant parts harvested: The stems, leaves, and latex are the primary parts of interest. However, harvesting the latex is a specialized process. There is no documentation on sustainable harvesting practices specifically for E. milii.

Caution: Given its toxicity, harvesting must be done with extreme care and protective clothing (gloves, eye protection). The plant is a common ornamental, making it a renewable source if cultivated.

12.3 Conservation Status

The IUCN status is Least Concern. The predicted extinction risk is not threatened. The plant is widely cultivated, ensuring its availability.

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13. Research Gaps and Future Directions

13.1 Critical Research Gaps

Human Clinical Trials: Clinical trials are completely lacking for all therapeutic claims. The plant's pharmacological profile is promising, but its high toxicity is a major barrier to clinical application. Research is needed to assess the feasibility of using purified, non-toxic compounds rather than crude extracts.

Pharmacokinetics: There is limited data on the absorption, metabolism, and bioavailability of key compounds.

Mechanistic Studies: The mechanism of action for many of its pharmacological properties remains to be fully elucidated. The discovery of the novel antiadipogenic mechanism is a step forward.

13.2 Future Research Priorities

Bioassay-guided Isolation: To identify the specific non-toxic compounds responsible for each activity, which could lead to the development of safe pharmaceuticals.

In vivo Studies: More in vivo animal studies are needed to confirm the in vitro findings.

Toxicology: Further investigation into the precise mechanism of toxicity and potential detoxification methods is a priority if the plant is to be developed further for medicinal applications.

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14. Commercial Applications

14.1 Pharmaceutical and Nutraceutical Potential

Euphorbia milii is a rich source of unique diterpenoids with a wide range of bioactivities. It has significant potential for:

· Developing novel anti-inflammatory drugs, particularly for conditions like psoriasis.

· Creating new anti-obesity and anti-diabetic agents from compounds like Euphomillanols A-E and the active stigmasterol derivative.

· Developing safe and effective molluscicides for schistosomiasis control programs.

· Sourcing potential anticancer agents.

14.2 Product-Specific Development

An anti-psoriatic Cream: The promising results from the psoriasis-like mouse model offer a potential path for developing a topical application for this common skin condition.

A Molluscicide: A natural, biodegradable molluscicide could be developed for use in endemic areas, which would be a major advancement in public health.

A Standardised Extract for Metabolic Disorders: A carefully standardised extract, possibly focused on the non-toxic diterpenoids, could be developed as a nutraceutical supplement for managing obesity and diabetes.

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15. Related Plants for Further Study

Jatropha curcas (Physic Nut): This plant belongs to the Euphorbiaceae family and, like E. milii, is known for its toxic latex and its use as a purgative, molluscicide, and for wound healing. Its medicinal potential is also hampered by its high toxicity.

Croton tiglium (Purging Croton): This plant belongs to the Euphorbiaceae family and is a classic example of a toxic medicinal plant. Its oil is a potent purgative and has been used traditionally, but its high toxicity requires extreme caution.

Bauhinia variegata (Orchid Tree): This plant belongs to the Fabaceae family. While from a different family, it is known for its anti-inflammatory and analgesic properties and has been studied for a range of conditions, including inflammation and cancer.

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16. Reference Literature

Primary Research

Chen, L., Cai, T.-T., Chen, H.-Y., et al. (2026). Traditional Herbal Medicine Euphorbia milii Des Moul: Research progress in chemical constituents and pharmacological activities. Journal of Ethnopharmacology, 368, 121772.

Song, Q.-Q., Guo, Y., Sun, P., et al. (2024). Skeleton Rearranged and Oxygenated ent-Rosane Diterpenoids with Antiadipogenic Activity from Euphorbia milii. Chinese Journal of Chemistry.

Rauf, A., et al. (2014). Preliminary phytochemical screening, antimicrobial and antioxidant activities of Euphorbia milli. Pak J Pharm Sci.

Fareed Hameed, et al. (2024). Effect of topical petroleum ether and ethyl acetate fractions from Euphorbia milii on imiquimod-induced psoriasis-like skin inflammation in mice. Pharm. Biomed. Res.

Giri, S., et al. (2024). Anticancer, Antidiabetic, Antioxidant Properties and Phytoconstituents of Efficacy of Methanolic Extract of Euphorbia milii Leaves. African Journal of Biological Sciences.

Sushma, D., et al. (2024). Exploring The Impact of Euphorbia Milii in The Medicine: A Comprehensive Review. International Journal of Pharmaceutical Sciences.

Conci, et al. (2021). Keratouveitis caused by Euphorbia milii sap: case report and overview. Rev. Bras. Oftalmol.

Key Monographs and Floras

e-Flora of Thailand: Provides a detailed botanical description for the Southeast Asian region.

Flora of China: Provides a detailed botanical description and medicinal use for the Chinese region.

Plants of the World Online (Kew Science): Provides comprehensive taxonomic, distribution, and conservation status data.

Hospital Authority, Hong Kong: Provides a critical overview of the plant's toxicology and poisoning symptoms.

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17. Disclaimer

Euphorbia milii is an extremely toxic plant. All parts of the plant, particularly the milky sap, are highly irritating and poisonous. This information is for educational and academic purposes only and is not a substitute for professional medical advice, diagnosis, or treatment.

Never ingest any part of this plant. Avoid all contact with the sap. Wear protective gloves and eye protection when handling the plant. Wash any exposed skin immediately with soap and water. If the sap comes into contact with the eyes, flush with water for at least 15 minutes and seek immediate medical attention.

Pregnant or nursing women should avoid any contact with the plant.

Always consult a qualified healthcare practitioner before using any plant for medicinal purposes.