Clematis

Clematis: A Comprehensive Reference

1. Identity and Botanical Classification

Genus and family: Clematis is a genus of mostly climbing perennial shrubs belonging to the family Ranunculaceae (the buttercup family). The genus comprises approximately 355 species and is composed mostly of vigorous, woody climbing vines and lianas, mainly distributed in the temperate regions of the Northern Hemisphere.

Etymology: The word "Clematis" is derived from the Greek klema, meaning "a vine branch," alluding to the vine-like twining climbing habit of the plant. The common name "Traveller's Joy" was coined by John Gerard for his English herbal of 1597.

Key medicinal species: While hundreds of species exist, a subset has commanded consistent medicinal attention across traditions. The most prominent include:

• Clematis chinensis Osbeck — Chinese clematis; the primary source of the TCM drug Wei Ling Xian
• Clematis mandshurica Rupr. — Manchurian clematis; also a source of Wei Ling Xian
• Clematis hexapetala Pall. — a third recognized source of Wei Ling Xian
• Clematis armandii Franch. and Clematis montana Buch.-Ham. ex DC. — sources of the TCM drug Chuan Mu Tong
• Clematis vitalba L. — "old man's beard" or "traveller's joy"; the primary European medicinal and folk species
• Clematis recta L. — "upright virgin's bower"; used in European herbal and homeopathic traditions
• Clematis virginiana L. — "woodbine" or "virgin's bower"; used in North American folk medicine

Wei Ling Xian and Chuan Mu Tong, both recorded in the Chinese Pharmacopoeia, are the most well-known Chinese herbal medicines obtained from Clematis species. Wei Ling Xian derives from C. chinensis, C. hexapetala, and C. mandshurica, while Chuan Mu Tong is from C. armandii and C. montana.

Common names: The genus includes hundreds of species of flowering vines, often recognized by common names such as virgin's bower, traveler's joy, and leather flower. Other common species names include woodbine (Clematis virginiana), old man's beard (Clematis vitalba), and vine bower (Clematis viticella).

Official pharmacopoeial name (TCM): The dried roots and rhizomes of the three Wei Ling Xian species are officially designated as Radix et Rhizoma Clematidis in the Chinese Pharmacopoeia. The TCM drug Radix Clematidis recorded in the Chinese Pharmacopoeia is isolated from the dried roots and rhizomes of Clematis chinensis Osbeck, Clematis mandshurica Rupr., and Clematis hexapetala Pall., and this drug has analgesic, sedative, antibacterial, anti-inflammatory, and diuretic effects according to the People's Republic of China Pharmacopoeia Commission (2005).

2. Common Preparations and Forms

Several species—especially Clematis vitalba, Clematis recta, and Clematis chinensis—have been used in traditional herbal medicine. Medicinal preparations typically focus on the roots or aerial parts, and are used in small, carefully prepared doses due to the plant's natural irritant properties.

Documented preparation forms across traditions include:

• Decoctions and water infusions: According to historical herbal sources, the roots and stems of C. vitalba were bruised and boiled for a few minutes in water and then digested for a while in sweet oil, making a preparation used as a cure for itch.
• Tinctures and liquid extracts: Alcoholic tinctures of dried root are found in Western herbal commerce. The NIH Dietary Supplement Label Database (DSLD) lists multiple marketed forms under names including "Chinese clematis root extract," "wei ling xian dried root liquid extract," and Clematis armandii stem extract.
• Poultices (topical): Traditionally, the leaves and stems were employed as topical remedies to ease joint pain, rheumatism, and skin irritations, and poultices made from Clematis vitalba were applied to affected areas to reduce inflammation and promote healing.
• Dried root powder: The Chinese Pharmacopoeia specifies the dried root and rhizome as the official drug form. Drying is important because it dissipates the most toxic constituent (protoanemonin — see Safety section).
• Homeopathic preparations: Clematis recta (also called Clematis erecta) is used in homeopathy. The homeopathic remedy Clematis Erecta is derived from the plant Upright Virgin's Bower (Flammula Jovis); the leaves and stems undergo a potentization process to prepare the homeopathic medicine.
• Cosmetic extract: An extract of the flowers, leaves, and stems of C. vitalba is used as an ingredient in commercial cosmetic preparations as a skin conditioner.

3. Traditional and Historical Use

3.1 Traditional Chinese Medicine (TCM)

Clematis is a botanical source for various pharmaceutically active components, which has long been used in conventional medicine since the beginning of Chinese civilization. Over 70 species are used in Chinese traditional medicine.

The dried roots and rhizomes of C. chinensis, named "Wei Ling Xian," have been used for thousands of years as a traditional Chinese medicine to treat rheumatic arthralgia, limb numbness, tendon constriction, and inconvenience in flexion and extension.

Roots, rhizomes, and stems of Clematis species are used to dispel wind-damp, unblock channels, and relieve pain. Wei Ling Xian and Chuan Mu Tong are recorded in the Chinese Pharmacopoeia.

Traditionally, Clematis medicine is used orally to treat syphilis, gout, rheumatism, bone disorders, and chronic skin conditions, and as a diuretic. In China, Clematis armandii and Clematis montana were traditionally used to decrease fever, induce urination, stimulate menstrual discharge, and promote lactation.

TCM practitioners also describe the herb's function in broader systems terms. Traditional applications described in classical texts include wind-dispelling and damp-eliminating, blood-activating and stasis-dispelling, damp-filtering and diuresis, heat-clearing, arthritis, traumatic injury, urinary tract infection, bones stuck in the throat, agalactia, abnormal menstruation, nephritis and edema, dysentery, and toothache caused by wind-fire.

Wei Ling Xian is prescribed as an analgesic, antipyretic, anticancer, and anti-inflammatory agent in the ancient books of East Asia, including Chinese Pharmacopeia and Donguibogam — the Korean traditional ancient book completed in 1613 by Jun Heo.

3.2 Korean Traditional Medicine

According to the Korean Herbal Pharmacopoeia, the roots and rhizomes of Clematis mandshurica Ruprecht are termed "Eaari" or "Wi Ryeong Seon," a traditional Korean herbal drug, and it is prescribed in order to dispel wind, remove dampness, and provide relief of pain.

3.3 European Folk Medicine

In European folk medicine, species like Clematis vitalba (commonly called "old man's beard") were used cautiously to address migraines, nerve pain, and chronic skin conditions, and infusions or tinctures were sometimes applied externally to relieve itchy or infected skin.

In herbal and homeopathic medicine, several European species of Clematis, being diuretic and diaphoretic, have been used in treating ulcerous diseases such as syphilis, gonorrhoea, cancer, and other inflammatory conditions including those of the eye (Grieve 1931).

During field works, researchers determined that different Turkish varieties of Clematis are frequently used as remedies in Anatolia, with the most salient folkloric application being for rheumatic ailments. In Northern Anatolia, Clematis cirrhosa and Clematis flammula leaves or the aerial parts are used to provide temporary relief of joint pains.

Different species of the genus Clematis from the Ranunculaceae family, rich in the glycoside ranunculin, are used in traditional Lebanese medicine, including Clematis flammula L. (virgin's bower), Clematis cirrhosa L. (fern-leaved clematis), and Clematis vitalba L.

Historical texts provided specific dosage guidance. A Modern Herbal records historical dosages of 1 to 2 grains of the extract per day, or 30 to 40 grains of the leaves in infusion per day.

3.4 North American Folk and Pioneer Medicine

The popular use of C. virginiana for skin disorders (sores, cuts), itching, and venereal eruptions in North American pioneer medicine was probably learned from American Indians. Throughout history, the leaf of the plant was also used in folk remedies for treating cancers and tumors, as well as for itching, fever, nephrosis, ulcers, and scrofula (Duke 1985). Past uses also indicate diuretic, rubefacient, sudorific, purgative, and vesicant properties.

3.5 Urogenital Applications in European Herbal Medicine

More specific internal applications included urogenital issues; Clematis recta was used for cystitis, urethritis, gonorrhoea, and inflammation of the testicles and bladder. Internal uses, though less common due to toxicity, were documented for conditions such as gout, fluid retention, and fevers, often as a diuretic.

4. Key Constituents and Active Compounds

A comprehensive survey of the literature revealed that triterpene saponins, alkaloids, flavonoids, lignans, steroids, coumarins, macrocyclic compounds, phenolic glycosides, anemonin, and volatile oils constitute the major classes of chemical constituents in the genus Clematis.

4.1 Triterpenoid Saponins (Dominant Class)

Triterpenoid saponins are mainly of interest in this genus as these are the most potent compounds responsible for most of the biological activities. Two principal aglycone types are recognized: oleanolic acid-type and hederagenin-type saponins. From the roots and rhizomes of C. chinensis alone, more than 40 triterpene saponins and lignans have been isolated.

A key compound is clematichinenoside AR (AR-6), a triterpene saponin isolated from C. chinensis. Researchers isolated multiple triterpene saponins (clematochinenosides) from the roots of C. chinensis and evaluated their inhibitory effects on COX-1 and COX-2 enzymes; several saponins demonstrated selective COX-2 inhibition, providing a molecular basis for the herb's traditional anti-inflammatory and analgesic properties.

Clematis hederagenin saponin (hederagenin 3β-O-α-L-arabinopyranoside, CHS) belongs to the class of triterpenoid saponins and has been isolated from Clematis ganpiniana.

4.2 Protoanemonin and Anemonin (Irritant Glycoside System)

The plant contains a glycoside called ranunculin, which is not toxic in itself but is quickly converted into the irritant substance protoanemonin when plant tissue is crushed, chewed, or damaged; this chemical conversion occurs through enzymatic action, releasing the toxic compound. Protoanemonin is classified as a vesicant, a compound that causes severe irritation and blistering upon contact with mucous membranes or the skin.

As a precursor of anemonin, ranunculin is enzymatically cleaved to remove saccharides and turn into protoanemonin; by polymerization, protoanemonin then turns into the dipolymer anemonin. Anemonin has been found to be inhibitory against Staphylococcus, Streptococcus, Bacillus diphtheriae, Mycobacterium tuberculosis, and E. coli.

Because protoanemonin is present mainly in fresh plant material, cooking or drying results in its decomposition. This toxicological distinction between fresh and dried plant preparations is critical from both a therapeutic and safety perspective.

4.3 Flavonoids

Compounds isolated from Clematis terniflora include 3,5,7,3′-tetrahydroxyflavone, 5,7,3′,5′-tetrahydroxy-dihydroflavone, apigenin, luteolin, and stigmasterol-3-O-β-D-glucopyranoside. The constituents identified from Clematis species include flavonoids, triterpenoid saponins, lignans, steroids, polyphenols, and coumarins; several flavonoids and alkaloids possess strong evidence of biological importance.

4.4 Lignans

Boehmenan, a lignan of Clematis armandii, has been shown to induce apoptosis in lung cancer cells through modulation of EGF-dependent pathways (Pan et al., 2016).

4.5 Other Constituents

Additional major chemical classes include macrocyclic compounds, phenolic glycosides, and volatile oils. Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside, isolated from C. tangutica, has been shown to attenuate myocardial ischemia/reperfusion injury via activating PKCε signaling (Zhu et al., 2017).

Around 90% of all 355 Clematis species have not been explored in phytochemistry, molecular biology, and pharmacology, which represents a significant potential source of undiscovered medicinal compounds.

5. Mechanisms of Action

5.1 Anti-Inflammatory Pathways

In animal studies, oral administration of AR-6 at doses of 8, 16, and 32 mg/kg for 7 days significantly reduced paw swelling and decreased levels of TNF-alpha and IL-1beta in blood; the anti-inflammatory mechanism appeared to involve suppression of NF-κB, TNF-alpha, and COX-2 expression in synovial tissue.

In in vitro studies, an ethanol extract of leaves of C. terniflora inhibited the essential inflammatory mediators, including nitric oxide, COX-2, TNF-α, IL-6, IL-1β, and inducible nitric oxide synthase (iNOS), by suppressing NF-κB and mitogen-activated protein kinase (MAPK) activation in macrophages.

5.2 Analgesic Mechanisms

The analgesic properties attributed to Clematis have been linked primarily to its triterpene saponins' inhibition of prostaglandin synthesis. In rats with adjuvant-induced arthritis, oral administration of AR-6 was associated with a reduction in clinical symptoms, absence of hyperplasia in synovial membranes, and decreases in prostaglandin E2 (PGE2), TNF-alpha, and nitric oxide levels.

5.3 Pro-Apoptotic (Cytotoxic) Pathways

Further investigation into the underlying mechanisms of apoptosis induction by CHS in breast cancer cells showed that the compound significantly reduced mitochondrial Apaf-1 and cytochrome c proteins in a time-dependent manner. Using a rat model of collagen-induced arthritis, AR-6 at 32 mg/kg significantly suppressed hind paw swelling and inhibited body weight loss; the compound worked by down-regulating TNF-alpha expression and inhibiting the PI3K/Akt signaling pathway in synovial tissue, suggesting a multi-target anti-inflammatory mechanism.

5.4 Diuretic Mechanisms

Infusions of the root and aerial part of Clematis montevidensis demonstrated moderate diuretic activity in rat studies, believed to be due to oleanolic acid isolated from the plant (Alvarez 2003).

6. Scientific Evidence by Area of Use

Important general caveat: The species of the genus Clematis emerged as a good source of traditional medicine for the treatment of various ailments; however, although few experimental studies have validated their traditional claims, most employed uncharacterized crude extracts. Such Clematis species need to be explored properly following bioactivity-directed fractionation with a view to isolating bioactive constituents and evaluating their possible modes of action.

6.1 Pain and Inflammation (Musculoskeletal)

Evidence level: Preclinical (animal and in vitro) only.

In animal pharmacology studies, Clematis brachiata extract exerted anti-inflammatory effects at doses of 100, 200, and 400 mg/kg on carrageenan-induced paw edema in rats, with the 400 mg/kg dose being the most potent. Antipyretic and antinociceptive effects were also noted, and specifically at 400 mg/kg, C. brachiata was found to lower body temperature more than indomethacin.

The triterpene saponin AR-6 from C. chinensis has been evaluated in multiple rat arthritis models, consistently showing reductions in paw swelling, pro-inflammatory cytokines, and joint histopathology. Despite extensive traditional use, robust, peer-reviewed human clinical trials supporting the medicinal efficacy of Clematis for pain and inflammation are notably absent.

6.2 Anti-Inflammatory Activity (Respiratory / Lung)

Evidence level: In vitro and animal only.

Leaves of C. terniflora have been used to cure various inflammatory diseases including tonsillitis, cholelithiasis, and conjunctivitis, and on this basis, a study was conducted to scientifically investigate the anti-inflammatory effect of an ethanol extract of the leaves using activated macrophages. The study found suppression of multiple pro-inflammatory mediators via NF-κB and MAPK pathways. No human clinical data exist for this indication.

6.3 Anticancer Activity

Evidence level: In vitro only. No clinical evidence.

Clematis hederagenin saponin (CHS) from C. ganpiniana showed cytotoxic effects on breast cancer cells in a dose- and time-dependent manner, and also induced apoptosis in breast cancer cells in a time-dependent manner. This research was carried out in cell lines, and studies on the active substances in Clematis with regard to anticancer effects remain scarce.

Boehmenan, a lignan from Clematis armandii, was found to induce apoptosis in lung cancer cells through modulation of EGF-dependent pathways in in vitro work. All available anticancer findings are from cell or animal studies with no translation to clinical evidence.

6.4 Antimicrobial Activity

Evidence level: In vitro only.

Anemonin, the dimerized form of protoanemonin formed during drying and storage of Clematis herbs, has been found to be inhibitory against Staphylococcus, Streptococcus, Bacillus diphtheriae, Mycobacterium tuberculosis, and E. coli in laboratory assays. Antimicrobial pharmacological activities have been reported across multiple Clematis species including C. chinensis, C. argentilucida, C. vitalba, and C. orientalis. No clinical antimicrobial trials have been published.

6.5 Diuretic Activity

Evidence level: Animal studies only.

The diuretic effects of Clematis montevidensis were investigated in rats administered isotonic saline solution; infusions of the root and aerial part demonstrated moderate diuretic activity, believed to be due to oleanolic acid isolated from the plant. Preliminary diuretic activity studies have been carried out on crude extracts of 26 traditionally used and medicinally promising Clematis species. No controlled human trials have evaluated diuretic efficacy.

6.6 Hepatoprotective Activity

Evidence level: In vitro and animal only.

Hepatoprotective pharmacological activities have been reported for C. chinensis, C. argentilucida, C. vitalba, and C. orientalis in preclinical settings. No human evidence is available.

6.7 Antidiabetic Activity

Evidence level: In vitro and animal only.

Antidiabetic pharmacological activities have been evaluated for extracts of C. vitalba, C. stans, C. tangutica, and C. graveolens. Preclinical patent-based research has proposed Radix Clematidis extracts for diabetes and insulin resistance applications, but no peer-reviewed clinical trials support this indication.

6.8 Antioxidant Activity

Evidence level: In vitro only.

The antioxidant potential of phenolic- and flavonoid-rich fractions of Clematis orientalis and Clematis ispahanica has been demonstrated in laboratory assays (Karimi et al., 2017). The clinical relevance of these in vitro findings is unknown.

6.9 HIV-1 Protease Inhibition

Evidence level: In vitro only.

Preliminary HIV-1 protease inhibitor activity studies have been carried out on crude extracts of 26 traditionally used and medicinally promising Clematis species. No clinical data exist for this application.

7. Body Systems and Health Areas

Based on the peer-reviewed literature, Clematis species have documented associations — ranging from traditional use to preclinical investigation — with the following body systems:

• Musculoskeletal system: The dominant area of traditional application and preclinical investigation; specifically for joint pain, rheumatism, gout, tendon disorders, and arthritis.
• Immune and inflammatory system: Modulation of NF-κB, COX-2, TNF-α, IL-1β, and IL-6 pathways demonstrated in cell and animal models.
• Urogenital system: Traditional texts document use for urinary tract infection, nephritis and edema, agalactia, and abnormal menstruation. C. recta was applied to cystitis, urethritis, and orchitis.
• Integumentary (skin) system: In folk medicine, Clematis is used topically for blisters and as a poultice to treat purulent wounds and ulcers.
• Gastrointestinal system: Traditional use as a purgative and to address dysentery.
• Oncological (experimental): In vitro studies on breast and lung cancer cell lines.
• Hepatic system: Preclinical hepatoprotective activity reported for several species.
• Metabolic system: Preliminary antidiabetic activity in cell and animal models.
• Respiratory system: The genus has been used in folk medicine for the treatment of asthma, among other conditions.

8. Dosage Forms and Dosages Reported in Studies

No clinical evidence supports dosage recommendations for clematis, and formal contraindications have not been identified based on clinical study data.

The following dosages appear in specific published sources and are presented as reported, not as recommendations:

• Animal pharmacology (anti-inflammatory): Clematis brachiata extract was tested at 100, 200, and 400 mg/kg body weight in rats for carrageenan-induced paw edema, with the 400 mg/kg dose being the most potent.
• Animal pharmacology (AR-6 saponin): Oral AR-6 was tested at doses of 8, 16, and 32 mg/kg for 7 days in a rat collagen-induced arthritis model.
• Historical European dosage: Historical texts record 1–2 grains of the extract per day, or 30–40 grains of leaves in infusion per day.
• Traditional Chinese medicine (dried root): The Chinese Pharmacopoeia specifies Radix et Rhizoma Clematidis (Wei Ling Xian) as the official drug form in dried preparation, though specific dose ranges are institution-specific and outside the scope of currently available English-language peer-reviewed sources reviewed here.

9. Safety Considerations

9.1 Protoanemonin: The Principal Toxic Compound

Formed from glycosides such as ranunculin when plant tissues are macerated, protoanemonin is a potent vesicant that primarily irritates the mucous membranes of the digestive system; effects on the urinary system, mammary glands, and brain associated with ingestion of especially large amounts of plant material have also been reported. Protoanemonin is subsequently polymerized to the inactive anemonin.

External exposure to the fresh sap can result in contact dermatitis, characterized by redness, burning sensations, and the formation of slow-healing blisters; this severe reaction is what traditional practitioners sometimes sought to elicit as a counter-irritation therapy.

Poisoning symptoms from fresh plant ingestion may include dizziness, confusion, possible fainting, and convulsions; fatalities are not common, probably due to the rapid and intense acrid taste and irritation resulting from oral contact.

9.2 Gastrointestinal and Systemic Toxicity

Whether by oral medication or topical use, natural herbs containing protoanemonin are irritant. With oral medication, they can result in severe gastroenteritis and intoxication symptoms such as nausea, vomiting, and diarrhea; they can even stimulate the kidney and cause bloody urine and proteinuria. They cause redness, swelling, and blistering when contacted with skin.

Fresh clematis can cause colic, diarrhea, and severe irritation to the stomach, intestines, and urinary tract when taken by mouth; the fresh plant is also unsafe when applied to the skin, as extended skin contact can cause slow-healing blisters and burns.

9.3 Drying Eliminates Protoanemonin

Protoanemonin is rapidly polymerized to the inactive anemonin when the plant material is dried. This is the basis for the traditional Chinese pharmacopoeial requirement that only the dried root and rhizome be used. Because protoanemonin is present mainly in fresh plant material, cooking or drying results in its decomposition.

9.4 Skin Contact

A case report describes a man aged 34 years who developed hypo- and hyperpigmented areas on his skin following application of fresh Clematis. All parts of the clematis plant — including leaves, stems, and flowers — contain irritant glycosides, primarily protoanemonin; when plant tissues are damaged, protoanemonin is released, which can cause irritation upon contact or ingestion.

9.5 Pregnancy and Lactation

It is considered unsafe to take fresh clematis by mouth or apply it to the skin during pregnancy or breast-feeding. Not enough is known about the safety of taking dried clematis by mouth or applying it to the skin during these periods.

9.6 Drug Interactions

No well-documented drug–drug interactions for clematis have been formally identified in the published literature. However, given the plant's ability to modulate COX-2, NF-κB, and PGE2 pathways as demonstrated in animal models, theoretical pharmacodynamic interactions with nonsteroidal anti-inflammatory drugs (NSAIDs) and immunomodulatory agents cannot be excluded. This has not been studied in humans.

9.7 Adulteration Risk

Wei Ling Xian is sometimes adulterated with the fibrous roots of Sheng Ma (Cimicifuga/Actaea species); research has identified significant differences between authentic Wei Ling Xian and Sheng Ma root adulterants in UV absorption, microscopic characteristics, and chemical profiles.

9.8 Emergency Management

If a large amount has been accidentally ingested, gastric lavage is recommended, followed by demulcents to soothe irritated membranes. Historical texts record camphor as moderating the too-violent effects of the drug.

10. Overall Evidence Assessment

Preliminary analgesic, anticancer, anti-inflammatory, diuretic, antiarthritis, hepatoprotective, hypotensive, and HIV-1 protease inhibitor activity studies have been carried out on crude extracts of 26 traditionally used and medicinally promising species of the Clematis genus. However, the totality of this research remains at the preclinical stage. Although few experimental studies have validated traditional claims, most employed uncharacterized crude extracts; such Clematis species need to be explored properly following bioactivity-directed fractionation with a view to isolating bioactive constituents and evaluating their possible modes of action.

Despite extensive traditional use, robust, peer-reviewed human clinical trials supporting the medicinal efficacy of Clematis are notably absent; modern research has primarily focused on isolating specific compounds and testing their potential biological activities in laboratory settings or animal models.

Being a potentially significant folklore medicine and pharmacologically active genus, clinical studies are needed to establish biological alternatives to synthetic drugs.

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