Guelder rose

Guelder Rose (Viburnum opulus L.): A Comprehensive Reference

1. Identity and Botanical Description

Viburnum opulus is a plant belonging to the Viburnum L. genus from the Adoxaceae family, sometimes placed in the monotypic family Viburnaceae, and formerly classified within Caprifoliaceae. It is known by a wide array of common names, including guelder rose, European guelder, European cranberrybush, water elder, rose elder, crampbark, snowball tree, and — particularly in Turkey — gilaburu.

The name "guelder" derives from Gueldersland, a Dutch province where the tree was first cultivated. Botanically, Viburnum opulus L. is a deciduous shrub growing to 4–5 m in height. It is common in natural habitats on the European continent and in some regions of North Africa and North Asia, and also in the central zone of Russia.

The plant is an upright shrub 1–3.5 m tall, bearing small white flowers in clusters. The leaves are dark green, have 3–5 lobes, and are approximately 6 cm wide at the broadest part. The fruit consists of small berries that are red to black in colour. The bark of V. opulus is green-brown on the outer surface and green-yellow to red-brown on the inner surface, with a strong characteristic odour and a somewhat bitter taste.

The American Herbal Pharmacopoeia® (AHP) recognizes two varieties of this medicinal species: V. opulus var. americanum (American) and V. opulus var. opulus (Eurasian). It is closely related to Viburnum prunifolium (Black Haw), and the two are often used interchangeably in herbal practice. Its constituents are similar to those of Viburnum prunifolium, though cramp bark contains approximately one-third of the resin found in Black Haw, and its properties are generally considered weaker.

Common Preparations and Dosage Forms

The bark of both V. opulus and related species is used medicinally and may be decocted, tinctured, or encapsulated as crude herb. Cramp bark is the dried bark of Viburnum opulus L. The bark is harvested from wild or cultivated trees and extracted using water, 70% ethanol, or glycerin-based solvents to produce liquid extracts, tinctures, or powders.

The bark, known as Cramp Bark, is employed in herbal medicine. It was formerly included in the United States Pharmacopoeia and subsequently introduced into the National Formulary in the form of a fluid extract, compound tincture, and compound elixir, for use as a nerve sedative and antispasmodic in asthma and hysteria.

V. opulus is a valuable decorative, medicinal, and food plant. In Russia and Ukraine, the red fruits — despite their astringent, bitter, and sour taste — are used in traditional cuisine as a component of marmalades, jams, cordials, liqueurs, and herbal teas. The raw fruit is slightly toxic but edible once cooked, and is used in Eastern traditional cuisine and as a cranberry substitute.

2. Traditional and Historical Use

Native American and North American Traditions

Traditional use is predominately in Northern America and Canada, where the plant was used by Native Americans as an anti-abortive, to remedy uterine prolapse, and as a spasmolytic for cramping pains in all parts of the body. Cramp bark has been used in European traditional medicine for over 200 years, as documented in the British Herbal Pharmacopoeia, primarily as an antispasmodic for menstrual cramps and muscle spasms. Native American and early European herbalists employed bark decoctions and tinctures for cramps, colic, and nervous conditions.

Eastern European and Slavic Traditions

The plant has an ancient cultural importance in Eastern Slavic countries and is one of the national symbols of Russia. An infusion of the bark is used in Russian traditional medicine to treat scrofula in children, asphyxia, colds, and uterine, gastric, and hemorrhoidal bleeding. The gilaburu juice is traditionally used to treat ailments such as cough, colds, tuberculosis, rheumatic aches, ulcers, liver disease, diabetes, and hypertension, as well as to prevent some stomach and kidney problems. The bark of V. opulus (Cortex Viburni) is also used in the treatment of stomach or uterine bleeding and hemorrhoids.

Turkish Folk Medicine

In Turkish folk medicine, the juice obtained by squeezing the fruits of V. opulus is taken orally to pass kidney stones. In inner Anatolia, a traditional drink named gilaburu has been prepared from the fruits of V. opulus. The fruits of V. opulus have been used to treat heart disease, coughs and colds, digestive troubles, bleeding, shortness of breath, high blood pressure, tuberculosis, duodenal ulcers, kidney and bladder infections, and menstrual and stomach cramp. It was also documented that V. opulus fruit juice and creams are used for ovarian cysts, painful periods, and urinary tract infections.

Western Herbal and Eclectic Medicine

Guelder rose is described as a powerful antispasmodic, used in the treatment of asthma, cramps, and other conditions such as colic or painful menstruation. It is also used as a sedative remedy for nervous conditions. Classically, V. opulus is used for pain radiating into the thighs, while the related V. prunifolium is considered specific for severe low back pain with a feeling of bearing down in the pelvis.

A paper read before the Materia Medica Society in 1882 by Dr. A. M. E. Purdy, later archived in PMC, discussed the use of Viburnum opulus for dysmenorrhoea and uterine pain by American physicians of the era. Contemporary physicians described Viburnum opulus as antispasmodic with a specific action upon the uterus. The concentrated tincture was administered in five- and ten-minim doses for these conditions, including as a preventative for threatened abortion.

3. Key Constituents and Active Compounds

Bark Constituents

The major identified constituents of cramp bark include: scopoletin — a coumarin and the major constituent responsible for antispasmodic action; viopudial — which contributes to antispasmodic action; viburnin — an antispasmodic bitter with specificity for the uterus and peripheral vasculature; and catechin and epicatechin — which contribute to the astringent activity of cramp bark and are used to differentiate the species from Viburnum prunifolium.

Viburnum opulus contains hydroquinones, coumarins, and tannins as primary constituents. Hydroquinone derivatives include arbutin and methylarbutin, as well as traces of free hydroquinone; viburnin is classed among the bitters.

Fruit Constituents

Generally, V. opulus has a diverse phytochemical profile with phenolic acids such as hydroxybenzoic and hydroxycinnamic acids, and three classes of flavonoids: flavonols, flavanols, and anthocyanins.

So far, three hydroxybenzoic acids, five hydroxycinnamic acids, three flavanols, nine flavonols, and ten anthocyanins have been identified in V. opulus fruits. In the above-mentioned groups, quantitatively dominant compounds are gallic acid, chlorogenic acid, quercetin 3-sambubioside, and cyanidin 3-xylosyl-rutinoside with cyanidin 3-glucoside, respectively.

The fruits are characterized by varied content of anthocyanins, with cyanidin 3-xylosyl-rutinoside, cyanidin 3-glucoside, and cyanidin 3-arabinosyl-glucoside as the main pigments among the ten identified compounds.

Proanthocyanidins are a quantitatively significant component of fresh V. opulus fruits, with content of 201–528 mg/100 g fresh weight, accounting for over 49.9% of total phenolics.

Analyses of V. opulus extracts revealed the presence of flavonols — including quercetin, rutin, luteolin and its glucoside, kaempferol, rhamnetin, and isorhamnetin — flavan-3-ols such as catechin and epicatechin, and hydroxycinnamic and hydroxybenzoic acid derivatives including vanillin, gallic, neochlorogenic, cryptochlorogenic, chlorogenic, protocatechuic, caffeic, trans-ferulic, and para-coumaric acids.

The plant is also known to contain iridoids, triterpenoids, diterpenoids, sesquiterpenes, coumarins, anthocyanins, phenolic acids, and organic acids. Among the main bioactive components are phenolic compounds, vitamin C, carotenoids, iridoids, and essential oils. The main volatile constituents in the fruits are alcohols, terpenoids, phenols, ketones, aldehydes, esters, branched fatty acids, and other acids.

Mechanisms of Action

Antispasmodic activity: Cramp bark contains the antispasmodic compounds scopoletin and viopudial, which relax smooth and skeletal muscle tissue by inhibiting calcium-mediated muscle contractions. The identification of scopoletin as an antispasmodic component was first published by Jarboe et al. (1967) in the Journal of Medicinal Chemistry. Viburnum opulus and the related V. prunifolium contain scopoletin, a coumarin which has a sedative effect on the uterus. Viopudial was separately characterised as both a hypotensive and smooth muscle antispasmodic from V. opulus by Nicholson, Darby, and Jarboe (1972) in the Proceedings of the Society for Experimental Biology and Medicine.

Hypotensive activity: The plant is described as a powerful smooth and skeletal muscle antispasmodic, and is hypotensive due to peripheral vasodilation caused by arterial smooth muscle relaxation.

Antioxidant activity: Antioxidant activity of V. opulus proanthocyanidins has been shown through suppression of lipid peroxidation, increase in endogenous NO generation, CAT and SOD activity, and a fall in MDA content.

Glucose and fatty acid transport modulation: Extracts revealed strong chemopreventive activity against oxidative stress induced chemically, as well as against DNA damage. Findings suggest V. opulus fruit as a dietary source of phytocompounds that could be considered as tailored food supplement components for the prevention and treatment of postprandial elevation of glucose and fatty acids through delaying the rate of glucose and fatty acid absorption by intestinal cells.

4. Scientific Evidence by Area of Use

4.1 Uterine and Menstrual Cramping (Dysmenorrhoea)

The antispasmodic activity of the bark in uterine smooth muscle is the most historically prominent claimed use of guelder rose. Cramp bark has been used in European traditional medicine for over 200 years, as documented in the British Herbal Pharmacopoeia, primarily as an antispasmodic for menstrual cramps and muscle spasms. Evidence for its antispasmodic effects derives primarily from in vitro studies demonstrating calcium channel antagonism by scopoletin and spasmolytic activity of viopudial in isolated tissue preparations.

Animal studies demonstrate that both V. opulus and V. prunifolium have relaxant effects on the uterus. A completed randomised controlled trial was registered at ClinicalTrials.gov (NCT02467543) by the University of Johannesburg to examine the efficacy of Viburnum opulus 3X in the treatment of primary dysmenorrhoea (completed December 2015); published results from this trial were not retrievable through public database searches at the time of writing.

The antioxidant capacity of V. opulus has been quantified in cell-free assays, but these findings have not been translated into clinical outcomes data. The overall evidence base for antispasmodic efficacy in humans remains at a traditional-use and preclinical level, warranting caution before drawing firm efficacy conclusions.

Widespread adulteration of Viburnum spp. preparations with Acer spicatum (mountain maple) yielded varying results in research trials conducted in the early 20th century regarding the efficacy of Viburnum opulus.

Evidence strength: Traditional-use and preclinical only. No adequately powered, peer-reviewed clinical trial results demonstrating efficacy in human dysmenorrhoea are currently published.

4.2 Endometriosis

Endometriosis is a gynecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. The fruits of Viburnum opulus L. have been used to treat gynecological disorders including primary and secondary dysmenorrhoea and ovarian cysts.

In an animal study, endometriosis was induced by suturing a piece of endometrium into the abdominal wall of Sprague-Dawley rats, followed by administration of fruit extracts sequentially prepared with n-hexane, ethyl acetate, and methanol. At the second laparotomy, the dimensions of endometrial implants were measured and intra-abdominal adhesions were scored. Fruits of V. opulus caused a reduction in endometriotic volumes and the levels of inflammatory and angiogenic factors in rat endometriosis. These effects were attributed to phenolic compounds, especially chlorogenic acid.

The results of this study indicate that the effectiveness of the fruit extract of V. opulus could be partially attributed to chlorogenic acid, with other phenolic compounds potentially potentiating the activity due to their quantity.

Evidence strength: Preclinical (animal model only). No human clinical trial data are available for endometriosis.

4.3 Urolithiasis (Kidney Stones)

In Turkish folk medicine, the juice obtained by squeezing the fruits of V. opulus is taken orally to pass kidney stones. In inner Anatolia, a traditional drink named gilaburu has been prepared from the fruits of V. opulus.

A study performed on Wistar rats with sodium oxalate-induced urolithiasis demonstrated that lyophilized ethanol extract obtained from V. opulus fruits and juice, administered orally at a dose of 100 mg/mL, induced a diuretic effect and reduced the level of oxalate, the main constituent of the stones. This was followed by elevation of kidney glutathione and total thiols parameters, as well as the reduction of lipid peroxidation and thiobarbituric acid reactive substances (TBARS).

It has been reported that the phenolic acid, ascorbic acid, and organic acid contained in the fruit of V. opulus can reduce urinary pH and prevent the formation of kidney stones, and that V. opulus phenolics can modulate cellular membrane dynamics.

One retrospective clinical study was published evaluating Viburnum opulus extract in the expulsive treatment of ureteral stones. The aim was to evaluate the efficacy of Gilaburu (Viburnum opulus) extract in the treatment of distal ureteral stones less than 10 mm. Data from 103 patients were retrospectively analysed. Patients were divided into two groups: those given V. opulus 1000 mg peroral 3×2 and diclofenac 50 mg peroral on-demand (n=53), and those given only diclofenac sodium 50 mg peroral on-demand (n=50). The analgesic requirement rate was significantly lower in the V. opulus group (24.5% vs. 44%, p=0.042).

The results of this preclinical study provided scientific evidence for the traditional usage of V. opulus in passing kidney stones in Turkish folk medicine.

Evidence strength: One retrospective human study (limited by non-randomised design) and multiple animal studies. Preliminary evidence only; prospective randomised controlled trials are lacking.

4.4 Gastrointestinal Mucosal Protection

Zayachkivska et al. investigated the influence of proanthocyanidins isolated from air-dried V. opulus fruits on gastrointestinal mucosal damage induced by water immersion and restraint stress in male Wistar rats. The results showed that V. opulus proanthocyanidins applied orally at doses of 25, 50, or 75 mg/kg body weight increased the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in gastric mucosa, inhibited the production of reactive oxygen species (ROS), and decreased the expression and tissue concentration of malondialdehyde derived from lipid peroxidation.

A study conducted on rats with induced hepatic damage assessed the hepatorestorative and protective effects of oligomeric anthocyanidins from Viburnum opulus. The study found that the complex of oligomeric anthocyanidins preserved glutathione, improved antioxidant action, and inhibited lipid peroxidation.

Evidence strength: Preclinical (animal and cell-based studies only). No published human clinical trial data are available for gastrointestinal indications.

4.5 Antidiabetic and Anti-Obesity Effects

Due to its strong antioxidant activity, the potential of V. opulus as a preventive agent against diet-related chronic diseases such as obesity and type 2 diabetes has been explored. Among the causes of these ailments is oxidative stress, as well as impaired glucose and free fatty acid (FFA) uptake. Research has determined the biological activity of V. opulus phenolic extracts as cytoprotective agents able to decrease induced oxidative stress, lower lipid accumulation, and attenuate glucose and FFA uptake by Caco-2 cells via GLUT2 and CD36/FAT transporters.

In vitro studies have demonstrated the antimicrobial, antidiabetic, anti-obesity, anti-inflammatory, and antioxidant activities of V. opulus.

Evidence strength: In vitro (cell-based) studies only. No human clinical data are available for these metabolic indications.

4.6 Antimicrobial Activity

The results of in vitro studies show the antimicrobial potential of cramp bark, especially against Gram-positive bacteria.

Evidence strength: In vitro only. No translational clinical data are available.

4.7 Immunostimulation

One in vitro study extracted water-soluble polysaccharides from the berries of Viburnum opulus. These were found to possess immunostimulating action, as they improved phagocytic activity and lysosomal enzyme secretion of macrophages.

Evidence strength: In vitro only.

4.8 Antiproliferative / Potential Anticancer Effects

The antiproliferative activity and cytotoxicity of V. opulus pomace (VOP) extracts were reported for the first time in a study of pressurized extracts. The ethanol extract (VOP-E) strongly inhibited cancer cell growth with an EC50 value of 0.39 ± 0.03 mg/mL, without adverse effects on normal epithelia. Procyanidins, catechin, epicatechin, hydroxybenzoic acids, anthocyanins, quercetin derivatives, as well as chlorogenic acid and its derivatives, are considered to contribute to the suppression of cancer cell growth.

Evidence strength: In vitro cell-line data only. No animal or human studies specifically addressing anticancer effects of V. opulus in isolation are currently published in peer-reviewed form.

5. Body Systems and Health Areas Associated with Guelder Rose

• Reproductive / Gynaecological system: Used for painful menstruation (dysmenorrhoea), uterine spasm, and related cramping.
• Musculoskeletal system: Used in the treatment of asthma, cramps, and colic.
• Urinary system: Used to prevent kidney and bladder stones and related disorders.
• Cardiovascular system: Described as hypotensive due to peripheral vasodilation caused by arterial smooth muscle relaxation.
• Gastrointestinal system: Traditionally used for stomach and digestive disorders, hemorrhoids, and ulcers.
• Nervous system: Used as a sedative remedy for nervous conditions.
• Respiratory system: Traditionally used for cough, asthma, and colds.
• Metabolic: Traditionally used for diabetes and hypertension.

6. Dosage Forms and Reported Dosages

Dosages described in the literature and historical pharmacopoeial records are as follows:

• Tincture (bark): The British Herbal Pharmacopoeia suggests 5 to 10 ml of tincture (1:5 in 45%) up to three times daily. Other references report tincture (1:5 in 40%) at 4–8 ml in a little water up to three times a day.
• Dried bark / capsules: Cramp bark is generally described as well tolerated at typical herbal doses of 300–500 mg dried bark extract, 2–3 times daily. Some sources report dried herb at 2 to 4 grams three times a day.
• Liquid extract (bark): Liquid bark extract of 2 to 8 ml taken three times daily has been reported.
• Decoction (bark): To make a decoction, 2 teaspoons of dried bark material are placed in one cup of boiling water and simmered gently for 15–20 minutes, to be drunk hot three times a day.
• Decoction (bark, traditional Russian use): The bark is recommended for internal administration at the dose of 1–2 tablespoons of decoction (10 g in 200 mL of water), taken 3–4 times per day as a diuretic or an antiseptic.
• Clinical trial dose (fruit extract, ureteral stones): In the retrospective clinical study on ureteral stones, the dose used was V. opulus 1000 mg peroral 3×2 (i.e., 1000 mg taken twice per each of three daily administrations).
• Animal study dose (fruit extract, urolithiasis model): In the rat urolithiasis model, lyophilized ethanol extract from V. opulus fruits and juice was administered orally at a dose of 100 mg/mL.
• Animal study dose (proanthocyanidins, gastrointestinal model): In the Wistar rat stress model, V. opulus proanthocyanidins were applied orally at doses of 25, 50, or 75 mg/kg body weight.

7. Safety Considerations and Known Interactions

Acute and Subacute Toxicity (Animal Data)

In a formal toxicity study, acute and subacute oral toxicities of V. opulus fruit juice were evaluated on Sprague-Dawley rats and BALB/c mice. In acute tests, a single administration of 2000 mg/kg body weight exhibited no clinical signs of toxicity or mortality, indicating that the LD50 was over 2000 mg/kg. In subacute tests, repeated administration for 28 days at 0 (control), 500, and 2000 mg/kg doses did not display adverse clinical signs or deaths. However, in the 2000 mg/kg subacute group, platelet counts were significantly elevated, and histopathological analyses revealed that the extract at 2000 mg/kg was toxic to the kidney, liver, and adipose tissue.

Raw Fruit Toxicity

The raw fruit is slightly toxic but edible once cooked, although very bitter. The berries of V. opulus are mildly toxic and can cause vomiting if eaten in large quantities.

Pregnancy

There is not enough reliable information to know if Viburnum opulus is safe to use when pregnant or breast-feeding. Due to its uterine-relaxing spasmolytic activity, it is contraindicated in early pregnancy despite traditional use for threatened miscarriage, as the safety profile in pregnant women has not been established by clinical research.

Coumarin Content and Anticoagulant Interaction

The coumarin content (scopoletin) of cramp bark raises a theoretical interaction concern with anticoagulant medications such as warfarin, as coumarins can potentiate blood-thinning effects, though direct pharmacokinetic interaction studies are lacking.

General Tolerability

Viburnum opulus is used for muscle cramps, diabetes, high blood pressure, and kidney stones, but there is no good scientific evidence to support these uses. When taken by mouth, there is not enough reliable information to know with certainty whether Viburnum opulus is safe to use or what all the side effects might be.

Adulteration Concerns

The lack of published information on the complete chemical composition of bark within the Opulus section, to distinguish V. opulus sourced from North America, Europe, and temperate Asia, is a known issue. Hybrids, ambiguity in sub-generic delineations, and lack of thorough chemoprofiling of bark material sourced from different continents make authentication and identification of extract material difficult.

Adequacy of the Evidence Base for Safety

The bark has been used clinically for a long time as a non-prescription medicine. However, the information available regarding its chemical and pharmacological effects is insufficient, and the bark should be studied in greater detail.

References

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