Viburnum

Viburnum: A Comprehensive Encyclopedic Reference

1. Identity, Botanical Classification, and Natural Sources

The name Viburnum designates a large genus of flowering shrubs and small trees belonging, according to modern classification, to the family Adoxaceae (previously classified under Caprifoliaceae). The genus comprises more than 230 species distributed across temperate and subtropical regions of both hemispheres. Within this broad genus, two species account for virtually all medicinal and dietary supplement use:

• Viburnum opulus L. — commonly known as cramp bark, guelder rose, water elder, European cranberrybush, and snowball tree. It is a deciduous shrub growing to 4–5 m high. This species is found in natural habitats in Europe, Russia, and some regions in North Africa and North Asia.
• Viburnum prunifolium L. — commonly known as black haw, blackhaw viburnum, stag bush, and sweet haw. It is native to eastern North America, from Connecticut west to eastern Kansas, and south to Alabama and Texas, and is a deciduous shrub or small tree growing to 2–9 metres tall.

These two species are closely related and sometimes confused; differences in chemical markers such as amentoflavone and catechin have been used to distinguish them. Hybrids, ambiguity in sub-generic delineations, and the lack of thorough chemoprofiling of bark material sourced from different continents make authentication and identification of extract material difficult.

Parts used medicinally: The bark of both species is used medicinally and may be decocted, tinctured, or encapsulated as crude herb. For V. opulus, the fruit (berry) is also an important source of bioactive compounds and is consumed in the form of juice, jelly, jam, and lyophilized extracts, especially in Eastern European and Turkish folk medicine. The health benefits of V. opulus result from the presence of bioactive components such as phenolic compounds, vitamin C, carotenoids, iridoids, and essential oils.

Common forms and preparations available as supplements: Both species are available as dried bark powder, aqueous decoctions, hydroalcoholic tinctures, and encapsulated crude herb. The fruit of V. opulus is additionally processed into lyophilized juice concentrates and standardized extracts.

2. Traditional and Historical Use

2.1 Viburnum prunifolium (Black Haw) — North American Traditions

Native Americans used a decoction of black haw to treat gynecological conditions, including menstrual cramps, aiding recovery after childbirth, and in treating the effects of menopause. Specifically, black haw was used by Cherokee and Delaware American Indian tribes as an antispasmodic for female reproductive complaints.

Black haw was first described in American botanical medicine in 1830 by a botanical physician who used it generally to relax cramps and spasms. It became popular among Eclectic physicians and physiomedicalists for relaxing cramps and spasms in asthma, hysteria, pains incidental to females, during pregnancy, and convulsions. These herbs have a long history of use as spasmolytics during pregnancy, especially for miscarriage, dating back well over a hundred years by Western herbalists, and even longer by Native American tribes.

Black haw was official in the United States Pharmacopoeia in 1882, its uses as an antispasmodic and preventative for miscarriage popularized by the Eclectic physicians. Its use was sufficiently common that black haw was officially recognized in the United States Pharmacopeia from 1882 to 1926 and in the United States National Formulary. Case reports of use for preventing abortion and/or miscarriage have also been noted historically in the British Medical Journal.

Eclectic physicians of the 19th century described specific indications for black haw in considerable detail. Specific indications included uterine irritability and hyperaesthesia, threatened abortion, uterine colic, dysmenorrhea with deficient menses, severe lumbar and bearing-down pains, cramp-like expulsive menstrual pain, intermittent painful contractions of the pelvic tissues, after-pains and false pains of pregnancy, and obstinate hiccough.

An 1878 publication in the medical literature described clinical experience with V. prunifolium as a uterine sedative. Dr. Jenks reported using it for over ten years in a great number of cases of threatened abortion, recommending it especially where abortion had become habitual with a woman. He also recommended it as a valuable therapeutic agent in the treatment of sympathetic disorders incident to pregnancy where a nervine or sedative was demanded, and found it useful in non-puerperal uterine disorders including menorrhagia, metrorrhagia incident to menopause, and all forms of dysmenorrhea attended with profuse menstruation.

2.2 Viburnum opulus (Cramp Bark) — European and Russian Traditions

In North America, the bark of the plant has traditionally been used to relieve cramps and is called cramp bark. Cramp bark was official in the USP from 1894 to 1916 and official in the NF from 1916. Cramp bark is included in the British Herbal Pharmacopoeia and is used by herbalists in the United Kingdom for miscarriage prevention.

In Eastern European and Russian traditions, V. opulus has been used differently, with greater emphasis on the fruit. An infusion of the bark is used in Russian traditional medicine to treat scrofula in children, asphyxia, and colds, as well as uterine, gastric, and hemorrhoidal bleeding. The bark has also been used to treat high blood pressure, heart trouble, tuberculosis, shortness of breath, stomach pain, digestive troubles, and duodenal ulcers.

In traditional folk medicine, the berries are used to treat numerous diseases and disorders such as coughs, colds, ulcers, kidney stones, dysmenorrhea, and high blood pressure, including bleeding, heart disease, neuroses, and diabetes. In Turkey, the fruit preparation known as gilaburu is particularly prominent. In Turkish folk medicine, the juice is obtained by squeezing the V. opulus fruit, and it is used to pass kidney stones.

3. Key Constituents and Active Compounds

3.1 Viburnum opulus — Bark

Viburnum opulus contains hydroquinones, coumarins, and tannins. Naturopathic and pharmacognostic sources describe the bark as containing viburnin (a bitter glycoside), valerianic acid, coumarins including scopoletin and scopaline, salicosides, resin, approximately 3% tannin, and the hydroquinone glycoside arbutin. Scopoletin, a coumarin, is primarily responsible for the antispasmodic effects. Viopudial aids in the treatment of spasms, while viburnin is an antispasmodic bitter compound specific to the uterus.

3.2 Viburnum opulus — Fruit

The fruit is a chemically rich and well-studied part of the plant. The fruits of V. opulus have a high content of phenolic compounds, including phenolic acids and flavonoids such as chlorogenic acid, catechins, quercetin glycosides, tannins, and anthocyanins. A comprehensive phytochemical analysis identified a much broader range of phenolics. Using HPLC and ESI-TOF MS methods, researchers identified chlorogenic acid as the free acid and many acids liberated from esters and glycosides including gallic, 4-hydroxybenzoic, protocatechuic, caffeic, ferulic, p-coumaric, and ellagic acids.

A pomace extract study covering 42 characterized compounds found that the major phytochemical groups were organic and phenolic acids, iridoids, quercetin and (epi)catechin derivatives, flavalignans, procyanidins, and anthocyanins.

The plant also contains iridoids — organic molecules from the monoterpenoid group. To our best knowledge, the structure of the V. opulus iridoids has been described in only three publications. The first concerns opulosides I–IV isolated from leaves, the second opulosides I–IV and additionally opuloside X present in fruits. The latest study on fruit pomace revealed the presence of six iridoids including secologanate and viburtioside derivatives.

Comparing plant parts, fruits contained the highest concentrations of fat, organic acids, sugars, soluble dietary fiber, and carotenoids, whereas the bark exceeded the remaining parts in antioxidant capacity, total and insoluble dietary fiber, and phenolic compounds (3.98 ± 0.04 g/100 g DW).

3.3 Viburnum prunifolium — Bark

V. prunifolium's primary constituents include coumarins, biflavones, and phenolic acids. The active components include scopoletin, aesculetin, salicin, 1-methyl-2,3-dibutyl hemimellitate, and viburnin. Tannin is another chemical component. More broadly, the bark contains flavonoids, coumarins (scopoletin), iridoid glycosides, triterpenes, phenolic acids (salicin, chlorogenic acid), tannins, and oleanolic and ursolic acid.

On the basis of phytochemical research, Viburnum species broadly contain iridoids, triterpenoids, coumarins, flavones, tannins, anthocyanins, phenolic acids, and organic acids.

3.4 Established Mechanisms of Action

The predominant pharmacological action supported by experimental data is smooth muscle relaxation and antispasmodic activity. The active principles are not fully established; however, it is thought that at least four active substances, including scopoletin and aesculetin, which have been identified, have uterine spasmolytic activity.

A 2009 Journal of Ethnopharmacology study investigated the mechanism directly. Viburnum prunifolium is used in ethnomedicine because of its spasmolytic, sedative, and anti-asthmatic properties; contrasting results were reported in past literature about its active principles. In both rabbit jejunum and guinea-pig trachea preparations, the order of potency was EtOAc fraction > BuOH fraction > MeOH extract, suggesting that major iridoids of the EtOAc fraction may be considered among the most active compounds. The iridoids were found to play a significant role in the biological activity of the corresponding fractions. Earlier research aimed to obtain complete relaxation of rat uteruses, which both black haw and cramp bark achieved; however, those authors suggested that black haw was not acting sympathomimetically (on adrenoreceptors), but was acting directly on the muscle.

For the antioxidant mechanism in V. opulus, 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. The antiurolithiatic mechanism is linked to hypoglycemic, antihyperlipidemic, anti-inflammatory, and antioxidant activities of chlorogenic acid. Antiurolithiatic activity could be related to the inhibition of oxalate levels and free radical production, as well as diuretic activity probably attributable to phenolic contents.

For the antidiabetic mechanism, among four tested samples, the ethyl acetate fraction not only had the highest content of total phenolics, but also possessed the strongest α-glucosidase inhibition, antiglycation, and antioxidant activities; it contained mainly chlorogenic acid, proanthocyanidin oligomers, and flavalignans. Anti-amylase activity of V. opulus fruits probably occurs due to proanthocyanidin polymers and chlorogenic acids.

For the ureteral smooth muscle mechanism, the relaxant, spasmolytic, and anticholinesterase properties of chlorogenic acid are expected to facilitate the passage of urinary stones.

4. Scientific Evidence by Area of Use

4.1 Dysmenorrhea and Uterine Antispasmodic Activity

This is the most historically prominent application for both species. Classically, V. opulus is used for pain radiating into the thighs and V. prunifolium is specific for severe low back pain with a feeling of bearing down in the pelvis.

Animal studies demonstrate that both herbs have relaxant effects on the uterus, and this effect has also been described in humans in studies of V. prunifolium. Because of the uterine relaxant and antispasmodic properties, V. opulus bark is used as a traditional medicine in the treatment of premenstrual syndrome to reduce menstrual fluid volume and decrease the pain associated with uterine contractions. Yet, there are no trials evaluating its efficacy in this regard.

Botanical dietary supplements for premenstrual syndrome (PMS) are less commonly used, and rigorous clinical trials have not been done. Examples include Viburnum opulus/prunifolium (cramp bark and black haw).

Evidence strength: The evidence for this application consists primarily of preclinical (in vitro and animal) studies and extensive historical case reports from the 19th century. There are no clinical trials to support these uses. The mechanistic rationale is plausible given established smooth-muscle relaxant activity, but formal human efficacy data are absent.

4.2 Urinary Tract Disease and Kidney / Ureteral Stones

This application has generated the most contemporary clinical research, particularly from Turkey where V. opulus (gilaburu) juice is a traditional remedy for kidney stones.

Preclinical (Animal): 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. Lyophilized juice of V. opulus (LJVO) and lyophilized commercial juice of V. opulus (LCJVO) exerted potential antiurolithiatic activity attributed to its diuretic effect along with the inhibitory action on oxalate levels and free radical production.

Clinical Study 1 (Retrospective): The first clinical trial evaluating the efficacy of V. opulus in the treatment of ureteral stones enrolled 103 patients referred to two different urology clinics due to distal ureteral stones <10 mm between January 2017 and June 2018. Patients were divided into two groups: those given V. opulus 1000 mg per oral 3×2 and diclofenac 50 mg per oral on-demand (n=53), and those given only diclofenac sodium 50 mg per oral on-demand (n=50). The authors concluded that V. opulus is a herbal treatment alternative that facilitates the passage of ureteral stones <10 mm, but prospective, randomized studies are needed to support these results.

Clinical Study 2 (Prospective): A subsequent prospective study compared V. opulus to the alpha-blocker tamsulosin, the standard medical expulsive therapy. The aim was to compare the extract of gilaburu (V. opulus) and tamsulosin as medical expulsive therapy in patients with distal ureteral calculi of 10 mm or less; data of 86 patients were prospectively collected. In the first group, V. opulus 1000 mg per oral 3×2 and diclofenac 50 mg per oral on-demand (n=43); in the second group, tamsulosin 0.4 mg per oral 1×1 and diclofenac 50 mg per oral on-demand (n=43). There was no difference between the groups in terms of stone expulsion rates and time until expulsion in all stones. Additional analgesic requirement and need for emergency admission were found to be lower in the V. opulus group (37.2% vs 65.1%, P=.017 and 11.6% vs 34.8%, P=.02, respectively). In a subgroup analysis of 5–10 mm stones, time until expulsion was shorter, additional analgesic requirement was lower, and need for emergency admission was lower in the V. opulus group than the tamsulosin group (7.1 ± 4.2 vs 11.8 ± 5.2 days, P=.005, 32.2% vs 77.7%, P=.001).

Evidence strength: Preliminary and limited. The prospective study is notable but small (n=86), and the retrospective study has inherent design limitations. The number of clinical studies is quite insufficient to understand the effects of V. opulus on humans.

4.3 Endometriosis

A study demonstrated V. opulus fruit potential in the treatment of endometriosis. In vivo studies performed on Sprague-Dawley rats with induced endometriosis by uterine tissue auto-transplantation were treated with extracts obtained from air-dried fruits at a dose of 100 mg/kg for 28 days. Among the studied samples, the ethyl acetate and methanol extracts decreased the sizes of endometric implants and their adhesion the most effectively.

In rat models with surgically-induced endometriosis, V. opulus significantly decreased the volume of endometriotic lesions and lowered the serum levels of IL-6, VEGF, and TNF-α. These effects were attributed to phenolic compounds, especially chlorogenic acid.

Evidence strength: Preclinical only (rodent models). No human clinical trials have been conducted for this indication.

4.4 Antioxidant Activity

Many of the health-promoting properties of V. opulus are associated with antioxidant activity, which has been demonstrated in both in vitro and in vivo studies. HPLC-DPPH scavenging assays revealed the presence of numerous antioxidants; the pressurized ethanol extract was a stronger antioxidant (equivalent to 0.77, 0.42, and 0.17 g trolox/g in ORAC, ABTS, and DPPH assays, respectively).

Evidence strength: Well-established in vitro and in vivo antioxidant activity, but no direct human clinical trials measuring clinically relevant antioxidant endpoints.

4.5 Antidiabetic / Glycemic Activity

In a published in vitro study, the inhibitory effects against carbohydrate digestive enzymes and non-enzymatic glycation, antioxidant capacity, and phenolic compounds composition of V. opulus fruits were evaluated. Among four tested samples, the ethyl acetate fraction not only had the highest content of total phenolics, but also possessed the strongest α-glucosidase inhibition, antiglycation, and antioxidant activities. LC–MS/MS analysis revealed chlorogenic acid as the major compound, and extracts showed strong α-amylase and α-glucosidase inhibition alongside high radical scavenging in DPPH and ABTS assays. Based on these findings, considering strong anti-glucosidase, antioxidant, and antiglycation activities, V. opulus fruits may find promising applications in nutraceuticals and functional foods with antidiabetic activity.

Evidence strength: Preliminary, in vitro only. No human clinical trials.

4.6 Antimicrobial Activity

The results of in vitro studies show the antimicrobial potential of V. opulus, especially against Gram-positive bacteria. Published in vitro studies indicate antimicrobial, antidiabetic, anti-obesity, anti-inflammatory, and anti-cancer properties of different morphological parts of V. opulus.

Evidence strength: In vitro only; clinical relevance is unknown and no human studies have been conducted.

4.7 Anti-inflammatory Activity

In cell-based studies, V. opulus demonstrated anti-inflammatory, anti-obesity, anti-diabetic, osteogenic, cardio-protective, and cytoprotective properties. Findings underscore the potential of V. opulus fruit phenolics to decrease bone tissue demineralization, and lower the secretion of pro-inflammatory cytokines, such as IL-6 and TNF-α, although they had no discernible effect on vascular endothelial growth factor (VEGF).

Evidence strength: Cell-based and animal data only; no controlled human trials.

4.8 Antiproliferative / Anticancer Activity

Pressurized ethanol extract of V. opulus berry pomace inhibited HT29 cancer cells at non-cytotoxic concentrations. Chlorogenic acid, the main identified phenolic constituent, and its microbial metabolites induced S-phase cell-cycle arrest and activated caspase-3 at 500–1000 µM concentrations in Caco-2 cells.

Evidence strength: Very preliminary, in vitro cell-line data only. No animal or human studies have been conducted specifically for oncologic endpoints.

5. Body Systems and Health Areas of Association

• Female Reproductive System: Uterine smooth muscle antispasmodic; dysmenorrhea, threatened miscarriage, menorrhagia, PMS — the primary historical and most extensively described application.
• Urinary System: Antiurolithiatic (kidney/ureteral stones), diuretic, reduction of urinary oxalate.
• Musculoskeletal System: Smooth and skeletal muscle relaxation for back pain, leg cramps, and general musculoskeletal spasm.
• Cardiovascular System: Hypotensive and vasodilatory activity attributed to scopoletin and salicin-related compounds; cardioprotective effects demonstrated in cell-based studies.
• Respiratory System: Ethnomedicinal use for anti-asthmatic properties.
• Metabolic / Endocrine System: Anti-diabetic (α-glucosidase and α-amylase inhibition) and anti-obesity effects in cell-based research.
• Gastrointestinal System: Antispasmodic for bowel cramping; astringent for diarrhea; historically for ulcers.
• Immune / Inflammatory System: Reduction of inflammatory cytokines (IL-6, TNF-α) demonstrated in cell-based and animal studies.

6. Dosage Forms and Reported Dosages

Dosages reported in the scientific and herbal medicine literature vary by species, plant part, and preparation:

Viburnum opulus (Cramp Bark)

• Tincture: 5 to 10 mL (1:5) three times per day. Encapsulated or decocted crude herb: 2 to 4 g three times per day.
• The bark of V. opulus is recommended for internal administration at the dose of 1–2 tablespoons of the decoction (10 g in 200 mL of water), taken 3–4 times per day as a diuretic or an antiseptic.
• In clinical trials (ureteral stones): V. opulus extract 1000 mg per oral 3×2 (i.e., 2000 mg three times per day) with diclofenac 50 mg on-demand.
• In antiurolithiatic animal studies: Lyophilized ethanol extract administered orally at a dose of 100 mg/mL.

Viburnum prunifolium (Black Haw)

• Tincture: (1:3 to 1:5) 5 to 10 mL three times per day.
• Decoction: 1 tablespoon per cup of water, 1–2 cups three times per day. Tincture (1:5; 60%): 5–10 mL three times per day. Powder: 2–5 g three times per day.
• There is no clinical evidence to provide dosing recommendations for black haw.

7. Safety Considerations and Interactions

7.1 General Safety Profile

The toxicity and safety of V. opulus juice have not been systematically studied until recently. In acute toxicity tests, a single administration of 2000 mg/kg body weight of extract to rats exhibited no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) was over 2000 mg/kg. In subacute tests, repeated administration for 28 days at 0 (control), 500, and 2000 mg/kg doses of extract in mice did not display adverse clinical signs or deaths. However, in the 2000 mg/kg subacute group, platelet counts were significantly elevated, which correlated with histopathological analyses.

V. opulus: There is not enough reliable information to know if it is safe to use or what the side effects might be. Black haw root bark is possibly safe when taken as a medicine.

7.2 Salicylate Content

Both species contain salicin, a salicylate precursor. Theoretically, salicylism — acute overdose of salicylates — can produce toxicity symptoms ranging from mild nausea, vomiting, abdominal pain, lethargy, tinnitus, and dizziness, depending on the dose consumed. Salicin and chlorogenic acid have been detected in V. opulus leaves and branches; dried leaves contained 0.90% of salicin and 0.68% of chlorogenic acid, while dried branches had more salicin (1.25%) but less chlorogenic acid (0.36%). Individuals with aspirin hypersensitivity or those taking anticoagulant medications should be aware of the salicylate content.

7.3 Oxalate Content

Black haw contains oxalates, but is generally given in doses far too low to warrant caution in patients with calcium oxalate nephrolithiasis. The oxalate content should nonetheless be noted for patients with a history of calcium oxalate kidney stones who are taking high doses.

7.4 Hypotensive Potential

Caution is warranted regarding V. prunifolium's use in hypotensive patients, as it is also used to treat hypertension. The scopoletin content of both species is understood to exert vasodilatory and hypotensive effects.

7.5 Pregnancy

It is possibly unsafe to use black haw when pregnant. Despite the historical use of both species to prevent miscarriage and manage pregnancy complications, this application carries inherent pharmacological ambiguity: the same uterine-relaxant activity invoked for miscarriage prevention could theoretically have adverse effects on uterine tone in late pregnancy. Large doses are reported in historical sources to sometimes produce nausea and vomiting, and by some observers are said to produce contraction of the uterine muscular tissue.

7.6 Overall Limitations of Safety Data

In the literature, no clinical safety data for V. opulus bark are reported from controlled clinical studies. The information available regarding chemical and pharmacological effects of the bark is insufficient, and the bark should be studied in greater detail. For V. prunifolium, contraindications have not been formally identified in the scientific literature.

8. Summary of Evidence Status

Viburnum species occupy a well-documented place in ethnobotanical history across North America, Europe, and Russia. The antispasmodic and uterine-relaxant uses of both V. opulus and V. prunifolium are supported by plausible phytochemical mechanisms and preclinical data but lack rigorous human clinical trials. The most clinically developed area of investigation is the use of V. opulus fruit extract for ureteral stone expulsion, where two small prospective and retrospective trials have yielded preliminary positive signals. The presence of secondary metabolites with different structures is reflected in pharmacological activity propped by in vitro and in vivo studies; its distinctive pharmacological activities include antioxidant, anti-inflammatory, antimicrobial, anti-obesity, antidiabetic, osteogenic, cardioprotective, and cytoprotective features. However, the number of clinical studies is quite insufficient to understand the effects of V. opulus on humans.

References

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