Bugleweed

Bugleweed (Lycopus spp.): A Comprehensive Reference

1. Identity, Taxonomy, and Botanical Description

Primary species: The principal North American species is Lycopus virginicus, a member of the mint family (Lamiaceae) known by many common names, including Virginia water horehound, American water hoarhound, sweet bugleweed, water bugle, carpenter's herb, green archangel, purple archangel, wolf foot, and Egyptian's herb. It is native to North America, where it is widespread in eastern Canada and the eastern United States. The closely related European species is Lycopus europaeus, commonly known as gypsywort or European bugleweed.

Other species used medicinally: Other species of Lycopus also go by the common name bugleweed, including L. americanus, L. europaeus, and L. lucidus. Other members of the Lycopus (water horehound), including Lycopus asper Greene, Lycopus unifloris Michx., and Lycopus virginicus L., are also broadly termed bugleweed.

Botanical characteristics of L. virginicus: This is a perennial herb with a hairy, squared stem reaching a meter tall. The oppositely arranged leaves have oval to lance-shaped blades with toothed edges. The leaves are dark green or purple. Clusters of tiny white or pink-tinged flowers occur in the leaf axils. The plant has a mint scent and a bitter taste.

Distinguishing the two primary medicinal species: L. europaeus and L. virginicus are considered by many to be medically interchangeable and share many common traits in appearance, though subtle botanical differences allow them to be distinguished. The smooth stems of L. virginicus may reach between 15–60 cm, in contrast to the longer and slightly hairy stems of L. europaeus, which typically grow to 30–100 cm. L. europaeus also has narrower leaves on a more acutely angled stem.

Interchangeability in practice: Both gypsywort (Lycopus europaeus) and bugleweed (Lycopus virginicus) are often used interchangeably within herbal medicine. The constituent profile and medicinal actions and indications of the two species are almost identical.

Genus name etymology: The genus name Lycopus derives from the Greek lykos, "wolf," and pous, "foot," in reference to the shape of the rhizomes.

Habitat and growth conditions: Bugleweed can grow on all soil types (sandy, loamy and clay) at varying soil pH levels. It needs a moist environment to develop and can grow profusely in flooded soil.

Parts used: The above-ground parts (leaves and flowers) are harvested for medicinal purposes.

2. Common Names and Synonyms

The plant is known by a wide array of common and vernacular names, including: bitter bugle, bugleweed, carpenter's herb, green archangel, gypsywort, northern bugleweed, Paul's betony, purple archangel, rough bugleweed, sweet bugle, Virginia water horehound, water bugle, water horehound, wolf foot, and wolfstrappkraut.

The juice of Lycopus yields a black dye that was supposedly used by gypsies to tan their skin, hence the name gypsywort.

3. Traditional and Historical Use

3.1 North American Traditional Use

Lycopus virginicus is used in the folk medicine of old Europe and by early American herbalists as a sedative and cough remedy and for tumultuous heart action.

The modern applications of bugleweed, unlike many medicinal plants, do not match its traditional use. Historically, bugleweed and related species were used to treat coughs and as a sedative.

Traditional uses of bugleweed include treatment of nosebleeds, heavy menstrual bleeding, and coughs. It has also been used as a sedative, astringent, and mild narcotic, and for tuberculosis characterized by bleeding from the lungs.

Eclectic medicine: Bugleweed was included in the materia medica of the Eclectic medicine practitioners, a movement founded in early 19th century North America. This movement was considered revolutionary at the time for their ethos of using plant-based medicines as an alternative to some of the more extreme medical practices of the day, such as prescribing toxic chemicals and extensive bloodletting. The study of plants native to the Americas compiled by these practitioners validated and recognized the knowledge and experience of traditional herbalists.

Bugleweed was considered by the Eclectics of the time as primarily indicated for conditions of the heart and lungs, specifically "vascular excitement, with rapid, tumultuous action of the heart but lacking power," along with any condition producing those characteristics.

3.2 European Traditional Use

Lycopus europaeus has been used in traditional medicine for centuries. Ancient herbalists and physicians, including those in Greek and Roman times, noted its potential for treating ailments related to the thyroid, heart, and blood circulation.

The plant was believed to have astringent properties, helping to reduce excessive bleeding and sweating. During the Middle Ages, it was widely used in European folk medicine to treat hyperthyroidism (notably Graves' disease) due to its mild goitrogenic effect.

Lycopus europaeus was used traditionally to cure coughs, respiratory disorders, and as a natural remedy for sleeplessness. It was also used as a natural treatment for hyperthyroidism and for some symptoms of Graves' disease, such as palpitations. It was also used in vascular excitement; hemorrhage, in small amounts, resulting from determination of blood to the lungs, kidneys, or gastro-intestinal organs; albuminuria with frequent pulse; cough with copious expectoration; and wakefulness with inordinately active circulation.

3.3 Preparation in Traditional Medicine

Herbalists typically use the aerial parts—the above-ground leaves and stems—harvested during flowering and prepared as a tincture, fluid extract, or dried herb.

Alcohol extract appears to be the most efficacious preparation, as it maximizes the amount of phenolic compounds (the constituents associated with the anti-thyroid activity).

4. Phytochemistry: Key Constituents

The active ingredients of Lycopus are not yet exactly identified. Among others, the following constituents have been isolated: hydroxycinnamic and caffeic acid derivatives, lithospermic acid, flavonoids, coumarins, tannins, saponins, sterols, terpenes, alkaloids, and essential oils.

More specifically, the phytochemical profile includes:

• Phenolic acid derivatives: caffeic, rosmarinic, chlorogenic, and ellagic acids; pimaric acid methyl ester, lithospermic acid and other organic acids. Additional compounds include flavone glycosides, volatile oil, tannins, and luteolin.
• Flavonoids: with a predominance of 7-O-β-D-glucuronides of apigenin, acacetin, and luteolin, tannins, rosmarinic acid and other phenolic acid derivatives including caffeic, chlorogenic and ellagic acids.
• Volatile oil content: approximately 0.2% essential oil, alongside fluorides, lithospermic acid, hydroxycinnamic acid derivatives (e.g. ferulic acid), caffeic acid derivatives, and rosmarinic acid.
• Additional constituents: alkaloids, coumarin, tannic acid, phenolic compounds, flavonoids, minerals, essential and volatile oils.

Lycopus contains rosmarinic acid, a phenolic compound derived from caffeic acid and found in several other Lamiaceae plants, all indicated historically for the symptoms of hyperthyroidism.

Rosmarinic acid and lithospermic acid are water-soluble and extracted efficiently in hot water infusions; fat-soluble terpenoids require alcohol extraction (tinctures) for meaningful concentration.

5. Mechanisms of Action

5.1 Antithyroid Activity

When thyroid-stimulating hormone (TSH) binds to the outer membrane of thyroid cells, it triggers a cAMP response on the inside of the cell via adenylate cyclase enzyme activation. Rosmarinic acid, and the related lithospermic and chlorogenic acids, may exert an antithyroid effect in cases of hyperthyroidism.

Rosmarinic acid seems to slow TSH-driven stimulation of thyroid cells via adenylate cyclase inhibition, and whole Lycopus extract may calm excessive thyroid stimulation, as with Graves' disease and autoimmune thyroiditis, via adenylate cyclase blockade. Rosmarinic acid also forms "adducts" with TSH, meaning that owing to particular electromagnetic affinities, rosmarinic acid forms loose bonds with endogenous TSH, thereby reducing its ability to bind and agonize TSH receptors.

Lycopus also inhibits the ability of Graves' autoantibodies to bind to TSH receptors and promote intracellular cAMP responses, thereby reducing adenylate cyclase–driven signal transduction and the resulting increase in thyroid hormone output.

Antithyroid activity was initially attributed to lithospermic acid; however, a more complex mechanism has developed since that early work. It has been proposed that the oxidation of phenolics to unstable orthoquinones by plant enzymes is required for antithyroid activity. Thus, caffeic acid, rosmarinic acid, and lithospermic acid are inactive without some form of oxidation.

5.2 Peripheral T4 Deiodination Inhibition

Aqueous extracts from Lycopus have been shown to have antihormonal components that inhibit the enzymatic deiodination processing of thyroxine outside of the thyroid gland, suggesting therapeutic value in the treatment of hyperthyroidism.

Bugleweed has antigonadotropic and antithyrotropic effects. It inhibits the peripheral de-iodination of T4. The phenolic constituents of the drug have an antigonadotropic effect. They cause a lowering of the prolactin level and have a depressant effect on the thyroid as a result of an inhibition of iodine transport and the release of preformed thyroid hormone.

5.3 Antigonadotropic and Prolactin-Modulating Effects

Extracts have been shown to decrease prolactin levels and to inhibit secretion of luteinizing hormone (LH) and follicle-stimulating hormone.

The active principle of Lycopus acts on certain pituitary hormones. In vitro, the effect of gonadotrophic hormones from different sources (adenohypophysis, PMS, HCG) as well as the effects of TSH are diminished or totally abolished by freeze-dried aqueous extracts of Lycopus virginicus.

5.4 Cardiovascular Effects

Bugleweed acts as a peripheral vasoconstrictor and has cardiotonic and cardio-active diuretic effects, increasing force of myocardial contraction and reducing heart rate.

In rats rendered hyperthyroid by administration of thyroxine, the increase in heart rate and blood pressure was significantly reduced, presumably by the reduction of the beta-receptor density in the heart.

6. Scientific Evidence by Area of Use

6.1 Mild Hyperthyroidism (Primary Area of Study)

The German Commission E issued a positive monograph for the drug in slight hyperthyroidism with vegetative-nervous disturbances. The Commission E monograph specifically covers mild hyperthyroidism with vegetative-nervous disorders, and a feeling of tension and pain in the mammary gland (mastopathy).

Animal studies: Extracts of L. europaeus administered to healthy rats reduced the weight of the thyroid, decreased thyroid hormone activity, and increased absorption and storage of iodine. The extract retarded goiter formation in propylthiouracil-treated rats.

High doses caused a reduction of TSH or thyroid hormone levels in animal experiments, whereas in hyperthyroid patients treated with low doses of Lycopus an improvement of cardiac symptoms was reported without major changes in TSH or thyroid hormone concentrations.

In one animal study, Lycopus extract was tested in thyroxine-treated hyperthyroid rats. Co-treatment with a hydroethanolic extract from L. europaeus started one week later than T4-application and lasted 5.5 weeks. Atenolol was used as a reference substance. The raised body temperature was reduced very effectively even by the low dose of the plant extract, whereas the reduced gain of body weight and increased food intake remained unaffected by any treatment. No significant changes of thyroid hormone concentrations or TSH levels were observed.

Key human clinical study (Beer et al., 2008, Phytomedicine): The aim of this prospective two-armed open study was to examine the effect of Lycopi europaei herba on thyroid function and on associated symptoms during a 3-month follow-up phase. The study population consisted of patients with a basal TSH below 1.0 mU/L and hyperthyroidism-associated symptoms. For the first time, the T3/T4 excretion in 24-hour urine was measured as a primary objective parameter. As secondary parameters, further hormones, the general condition and symptoms associated with hyperthyroidism were registered. The urinary T4 excretion was significantly increased in Lycopus europaeus-treated patients (p=0.032). It is supposed that renal mechanisms cause the increased T4 excretion either by a modification within the glomeruli or by impaired reabsorption.

Second observational cohort study: Another clinical cohort study evaluated clinical outcomes in groups of hyperthyroid patients using Lycopus extracts in various time frames, compared with a cohort of hyperthyroid patients receiving no treatment. The groups receiving L. europaeus were associated with a statistically significant and clinically relevant improvement of the symptoms in mild hyperthyroidism.

A daily dosage of Lycopi europaei herba 40 mg/day taken in divided doses was used for 3 months in an open-label clinical study for mild hyperthyroidism. Low-dose powdered L. europaeus equivalent to 2 × 5 mg Lycopus extract used in an observational study produced no changes in thyroid hormone levels but was associated with improved cardiac symptoms.

Evidence strength assessment: Scientific research on bugleweed's efficacy and safety, particularly in human clinical trials, is somewhat limited. While traditional use is extensive and anecdotal evidence suggests benefits, more robust and large-scale studies are needed to substantiate its therapeutic claims. In clinical studies, significant changes of thyroid parameters were not seen, though an improvement of cardiac parameters was reported in one observational study. Overall, the available clinical evidence consists of small non-randomized open-label studies, which significantly limits its strength.

6.2 Cardiac Symptoms Associated with Hyperthyroidism

All Lycopus species used medicinally are used in similar ways for hyperthyroid-like symptoms including heart palpitations and tachycardia, chest tightness, tremor, anxiety, and insomnia.

Animal studies have indicated that Lycopus europaeus can reduce elevated heart rate, blood pressure, and hyperthermia in models of hyperthyroidism. However, clinical evidence for isolated cardiac endpoints is limited to symptom observations within the hyperthyroid studies described above.

6.3 Mastodynia (Breast Pain) and Premenstrual Syndrome

Therapeutic efficacy in mastopathy has been reported. The Commission E monograph includes a feeling of tension and pain in the mammary gland (mastopathy) among the recognized indications.

Bugleweed may reduce levels of the hormone prolactin, which is primarily responsible for breast milk production. Elevated levels of prolactin may also cause breast pain in women; based on this finding, bugleweed has been recommended for cyclic mastalgia (breast pain linked to menstrual cycles) and symptoms associated with premenstrual syndrome.

A reduction of prolactin levels in rats following Lycopus extract administration has been observed, while no effect on plasma levels of prolactin was found in a clinical study. This discrepancy between animal and human data limits the strength of the prolactin-lowering rationale for clinical mastodynia.

6.4 Sedative and Nervous System Effects

Lycopus europaeus possesses, among other effects, hypnotic properties along with antimicrobial, antiparasitic, antioxidant, anti-inflammatory, analgesic, antitussive, and anti-diarrheal activities. These have been identified primarily through in vitro and animal pharmacological work; human clinical evidence for sedative endpoints remains absent from published literature.

6.5 Respiratory and Antitussive Effects

Traditionally, the herb has been used to cure coughs and respiratory disorders. It is also thought of as a natural remedy for sleeplessness. These uses are based on historical and folk-medicine records; no dedicated clinical trials of bugleweed for cough or respiratory indications have been identified in the published literature.

7. Body Systems Associated with Bugleweed

• Endocrine system (thyroid): The most extensively studied action; involves TSH receptor antagonism, adenylate cyclase inhibition, inhibition of peripheral T4-to-T3 conversion, and reduction of Graves' immunoglobulin binding.
• Cardiovascular system: Reduction of tachycardia, heart palpitations, and blood pressure elevations associated with hyperthyroid states; peripheral vasoconstriction.
• Reproductive / endocrine system: Antigonadotropic effects with inhibition of LH and FSH; reduction of prolactin; proposed role in mastodynia and PMS.
• Nervous system: Traditional use as a mild sedative and nervine, used for anxiety, insomnia, and nervous tachycardia.
• Respiratory system: Historical use as an antitussive for irritating coughs and respiratory complaints.
• Urinary system: Documented diuretic action.

8. Dosage Forms and Reported Dosages

Bugleweed is commercially available in several forms. Tinctures and fluid extracts are traditionally prepared at 1:2 to 1:5 herb-to-solvent ratios; commercial products vary.

German Commission E recommendation: The German Commission E monograph recommends 1–2 grams of the whole herb per day. Intake of tincture should be limited to 1–2 ml three times a day. Bugleweed is often combined with other herbs used to treat mildly overactive thyroid function, including lemon balm (Melissa officinalis) and gromwell (Lithospermum ruderale).

Dosages from clinical studies (as reported in sources):

• A daily dosage of Lycopi europaei herba 40 mg/day taken in divided doses was used for 3 months in an open-label clinical study for mild hyperthyroidism.
• Low-dose powdered L. europaeus equivalent to 2 × 5 mg Lycopus extract was used in an observational study.
• Lycopus is generally considered safe and can be taken at doses ranging from 100 to 400 mg at a time for two to three times each day. Higher doses of 2 g or more a day have been well tolerated.

Bugleweed is used to treat mild hyperthyroidism, premenstrual syndrome, and breast pain; however, quality clinical studies are lacking to support these uses. Clinical trials are lacking regarding dosages for specific clinical applications.

Alcohol extract appears to be the most efficacious preparation as it maximizes the amount of phenolic compounds.

9. Safety Considerations and Interactions

9.1 General Tolerability

The few clinical studies that have been done report Lycopus to be well tolerated and without significant side effects.

9.2 Long-Term Use and Abrupt Discontinuation

Long-term use of bugleweed can cause an enlarged thyroid gland. Discontinuing bugleweed abruptly can result in high levels of thyroid and prolactin, which might cause physical symptoms.

Bugleweed should not be abruptly discontinued; instead, gradually tapering down dosage is recommended if treatment is to be stopped for any reason.

9.3 Contraindications

Bugleweed is contraindicated in underactive thyroid (hypothyroid conditions such as Hashimoto's disease), cases of thyroid enlargement with no functional disorder, pregnancy, and lactation.

It is contraindicated in pregnancy and lactation because of the potential for antigonadotropic and antithyrotropic effects, as demonstrated in animal experiments.

Bugleweed is not considered safe for use during pregnancy or whilst breastfeeding. Along with herbs such as sage (Salvia officinalis), it may decrease milk supply in breastfeeding people. Due to the lack of clinical data, it is also advised that bugleweed not be given to children due to its antithyroid and antigonadotropic actions.

Bugleweed should not be given to children. Persons with thyroid tumors, hypopituitarism, pituitary adenoma, hypogonadism, congestive heart failure, or hypothyroidism should avoid the use of this herb.

9.4 Fertility Concerns

Women who are trying to conceive are cautioned against taking preparations containing bugleweed, as there is evidence to suggest it may possess contraceptive effects with longer-term usage.

9.5 Drug Interactions

Lycopus decreases the effects of levothyroxine by pharmacodynamic antagonism; this interaction is considered contraindicated. The mechanism is blockade of peripheral conversion of T4 to T3.

Lycopus increases the effects of radioactive iodine by pharmacodynamic synergism. This interaction requires caution and monitoring, as Lycopus blocks peripheral conversion of T4 to T3.

Bugleweed should not be taken concurrently with any thyroid-modulating drugs, as it may reduce the intended therapeutic effects. It may also interfere with thyroid diagnostic procedures that use radioactive isotopes.

Lycopus increases the effects of methimazole by pharmacodynamic synergism, requiring close monitoring.

Bugleweed might lower blood sugar. If someone has diabetes, bugleweed should be used cautiously, with careful monitoring of blood sugar.

References

• Beer AM, Wiebelitz KR, Schmidt-Gayk H. Lycopus europaeus (Gypsywort): Effects on the thyroidal parameters and symptoms associated with thyroid function. Phytomedicine. 2008;15(1-2):16-22. ScienceDirect.
• Vonhoff C, et al. Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats. Life Sciences. 2006;78(10):1063-70. ScienceDirect.
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