White dead nettle flower

White Dead Nettle Flower (Lamium album L.): A Comprehensive Reference

1. Identity and Botanical Profile

Taxonomy and Nomenclature

Lamium album, commonly known as white dead nettle, is a plant in the family Lamiaceae. The formal pharmacopoeial name for the dried flower drug is Lamii albi flos, while the whole herb drug is designated Lamii albi herba. The common name "dead nettle" refers to the superficial resemblance of Lamium species to the unrelated stinging nettles, but unlike those, they do not have stinging hairs and are therefore harmless, or apparently "dead."

Within the family Lamiaceae, the genus Lamium is herbaceous and possesses annual or perennial forms, comprising around 40 species found in temperate and subtropical regions of Africa, Asia, and Europe. Lamium album is the most extensively studied species of the genus and the one addressed by regulatory monographs.

Natural Distribution

Lamium album, commonly known as white dead nettle or non-stinging nettle, is a flowering herbaceous plant native throughout Europe, Western Asia, and North Africa. The International Union for Conservation of Nature (IUCN) European assessment of Lamium album listed it in 2013 as "Least Concern," stating that white dead nettle is a widespread and common species with stable populations and no significant threats.

Botanical Description

Lamium album L. is a perennial herb. Regarding its botanical aspects, the leaves are cordate or reniform, ovate to lanceolate with an acute apex and cordate base, being petiolate on the lower nodes and sessile or uncommon amplexicaule at the upper nodes. It presents inflorescences with verticillasters in the axils of the floral leaves (2–12 flowered). The calyx is campanulate or tubular with subequal teeth.

Drug Part and Common Preparations

Lamii albi flos is a drug obtained from the dried petals with attached stamens. In practice, preparations are made from the flowers or, less commonly, the aerial herb. Nowadays, L. album is used to make beverages such as tea and dietary supplements that claim to detoxify the organism and prevent menstrual disorders, abdominal inflammation, and musculoskeletal diseases. The plant's young shoots, leaves, and flowers are also edible fresh or cooked. The aerial parts have also been used as alternative nourishment during starvation seasons in different countries of Asia and Europe, in particular in Turkey, China, and Japan, where the leaves and flowers are consumed raw or cooked and used as a spice and/or specific ingredient of Mediterranean dishes.

2. Traditional and Historical Use

European Folk and Herbal Medicine

From ancient times, this plant has been endowed with revival, curative, and culinary virtues. In the past, in traditional and folk medicine, white dead nettle was used mainly for its anti-inflammatory, astringent, and antiseptic activity.

In humoral terms, Lamium album was classified by Culpeper as hot and dry, and he astrologically classed it as a herb of Venus, being therefore primarily used by women. Traditional actions attributed to the plant historically include being drying, warming (as noted by Hildegard of Bingen), astringent, expectorant, and haemostatic.

Its anti-inflammatory, astringent, and antiseptic activity is especially utilized in the treatment of menorrhagia, uterine hemorrhage, vaginal and cervical inflammation, and leucorrhoea. For this reason, it is often called the medicine of women's afflictions. However, it is also considered effective in chronic bronchitis or pharyngitis because of its mucolytic and antispasmodic activity. Moreover, Lamii albi flos is applied in skin inflammation, alimentary or urinary tract diseases, and is said to facilitate the removal of harmful products of metabolism.

The German Commission E Monographs list clinical applications of the herb including use for gastro-intestinal ailments such as mucosa irritation, wind, and fullness. In empirical medicine, it was also applied for gastrointestinal complaints, bloating and flatulence, as an expectorant for catarrh, for menopausal disorders, and as a poultice (boiled) for skin swellings, varicose veins, and gouty nodules.

Asian Traditional Medicine

In the traditional medicine of Asia, L. album has been used for the treatment of a number of diseases such as trauma, fracture, paralysis, leucorrhoea, hypertension, women's pain, uterine hemorrhage, menorrhagia, and vaginal and cervical inflammation. Some Lamium plants have been used in folk medicine worldwide as a remedy in the treatment of several disorders, such as trauma, fracture, paralysis, hypertension, menorrhagia, and uterine hemorrhage.

Regulatory Recognition of Traditional Use

According to the specifications of the German Commission E, the drug is used in herbal medicinal products for the treatment of catarrhal diseases of the upper respiratory tract, mild oral mucositis and pharyngitis, and is also used externally for superficial skin inflammations. In the Commission E Monographs, a distinction is made between the flowers of Lamium album (classified as an approved herb) and the herb (unapproved). Specifically, for internal use the Commission E daily dose is 3.0 g; for external use it is 5.0 g, with Lamii albi flos mostly used in the form of infusions or as a sitz bath (5.0 g per sitz bath).

Preparations from the flowers or herb of the white dead nettle (Lamium album L.) are recommended for the treatment of upper respiratory tract disorders or as a topical medication for mild inflammation of the throat, mouth, and skin.

3. Key Constituents and Active Compounds

Overview of Chemical Classes

A wide range of constituents is found in L. album, including flavonoids and phenolic acids, fatty acids, iridoids, triterpenes, saponins, polysaccharides, essential oils, tannins, phytoecdysteroids, and mucilage. The presence of these chemicals, i.e., hydroxycinnamic acids, iridoids, secoiridoids, flavonoids, anthocyanins, phenylpropanoids, phytoecdysteroids, benzoxazinoids, and betaine, can provide biological activities.

Iridoids

Iridoids are one of the main constituents and potential chemotaxonomic markers in representatives of the genus Lamium. These secondary metabolites are monoterpenes consisting of an iridane skeleton. They mainly occur as glycosides. The following glycoside iridoids have been identified in various Lamium species: lamalbide, albosides A and B, lamalboside and acteoside, hemialboside, lamiol, caryoptoside, shanzhiside methyl ester, barlerin, 5-deoxylamiol, phytoecdysone, 24-epi-pterosterone, and penstemoside.

The most abundant compounds in both aqueous and ethanolic-aqueous extracts of the flower are lamalbid, chlorogenic acid, and verbascoside. In particular, lamalbid appears to be a remarkable chemotaxonomic marker of L. album. Quantitatively, lamalbid was the most abundant compound both in aqueous (39.09 ± 1.02 mg/g dry weight) and ethanolic-aqueous (26.66 ± 0.64 mg/g dry weight) extracts.

A phytochemical study of the aqueous extract of the flowering tops of Lamium album led to the identification of the antiviral iridoid isomers lamiridosins A and B. These compounds were found to significantly inhibit hepatitis C virus entry (IC₅₀ 2.31 µM) in vitro.

Phenylpropanoids

Phenylpropanoids have been established as the most diverse class of compounds in the flowers and herb of L. album. Lamalboside, also named lamiuside A, has been recognized as the most characteristic phenylpropanoid ester of L. album, in addition to verbascoside. Three phenylpropanoid glycosides, verbascoside, cis-acteoside, and lamalboside (lamiuside A), were primarily reported in Lamium album L., while more recent work showed the presence of additional phenylpropanoids such as lamiusides B, C, and E.

Phenolic Acids and Flavonoids

Six types of glandular trichomes were found in the flower which contained flavonoids, phenolic acids, and tannins. Phytochemical studies demonstrated the presence of caffeic, chlorogenic, ferulic, gallic, p-coumaric, protocatechuic, syringic, gentisic, and vanillic phenolic acids, as well as rutoside and isoquercetin. Flavonoids identified include rutin, quercetin malonylhexoside, and tiliroside in aqueous and ethanolic-aqueous extracts of Lamii albi flos.

Phytoecdysteroids

Ecdysteroids from the aerial part of L. album stimulate protein synthesis and immune response, lower blood cholesterol and glucose concentrations, and have antimutagenic, antioxidant, and wound-healing properties.

Other Noteworthy Compounds

The plant contains tannins, and also histamine, choline, and tyramine — biogenic amines that probably explain the anti-haemorrhagic action of the plant and its similarity in this context to Capsella bursa-pastoris. In all Lamium species tested, an unusually high squalene content is detected, which has significant biological activity — including antibacterial, antitumor, and immunostimulatory effects.

4. Mechanisms of Action

Anti-Inflammatory Mechanisms

The aim of one key in vitro study was to screen for the anti-inflammatory bioactivity of compounds isolated from the aqueous-methanolic extract of Lamium album herb in human neutrophils (PMNs), specifically examining the effect of compounds on the inhibition of cytokines (IL-8, TNF-α) released by neutrophils. Phenylpropanoids (verbascoside and phlinoside D), as well as iridoids (lamalbid and shanzhiside methyl ester) and flavonoids, were found to be more significant inhibitors of IL-8 secretion than TNF-α. The compounds at a concentration of 25 µM, except for shanzhiside methyl ester, inhibited secretion of IL-8 in the range from 29.1 to 50.0%.

All tested compounds, except for astragalin, at the concentration of 25 µM, significantly inhibited the oxidative burst in stimulated PMNs. The most relevant inhibitors were derivatives of quercetin; cells treated with these compounds generated 16.9 ± 1.2% and 10.0 ± 2.6% ROS, respectively, compared to control cells (104.5 ± 8.3%), results similar to quercetin used as a positive control.

Many bioactivities including antioxidant, anti-inflammatory, immunomodulating, and antimicrobial have been assigned to iridoids. It was shown that lamalbid, at a concentration of 125 µg/mL (corresponding to 296 µM), inhibited ROS generation by 57%, but did not affect iNOS and NF-κB activity.

Antioxidant Mechanisms

Iridoids as a major constituent and as glycosides exhibit biological activity such as antiarthritic, anti-inflammatory, antibacterial, anticancer, antioxidant, antiviral, immunomodulatory, wound-healing, and neuroprotective activities. Aerial parts of white dead nettle have flavonoids which protect normal human skin fibroblasts against oxidative stress–induced cell injury.

Haemostatic Mechanisms

The plant contains histamine, choline, and tyramine, which probably explain the anti-haemorrhagic action of the plant. The flavonols may also contribute to the plant's haemostatic action.

Digestive Mechanisms

White dead nettle contains bitter iridoid constituents, which are responsible for its stimulating effect on digestion and in supporting liver function.

5. Scientific Evidence by Area of Use

5.1 Anti-Inflammatory Activity

In vitro evidence: A study screened for the anti-inflammatory bioactivity of compounds isolated from an aqueous-methanolic extract of Lamium album herb in human neutrophils (PMNs). The effect of compounds on the inhibition of inflammatory markers IL-8 and TNF-α was studied. Molecular masses and purity were determined using HPLC-DAD-MSⁿ. Cytokine production after incubation with the compounds at concentrations of 1–25 µM was measured by ELISA. Phenylpropanoids (verbascoside and phlinoside D), as well as iridoids (lamalbid and shanzhiside methyl ester), and flavonoids proved to be more significant inhibitors of IL-8 secretion than TNF-α.

Experiments have shown anti-inflammatory, weak diuretic, and antimicrobial activity which could be attributed to the iridoids, tannins, and triterpene saponins.

Evidence strength: Current evidence is derived primarily from in vitro cell models and preclinical studies. No dedicated human clinical trials have isolated and confirmed the anti-inflammatory effects of L. album flower preparations alone.

5.2 Antimicrobial Activity

In vitro evidence: The antimicrobial activity of 18 different extracts from in vivo and in vitro grown L. album plants was evaluated against clinical bacteria and yeasts using the well diffusion method. All extracts demonstrated antibacterial activity, whereas only the water extracts from leaves (in vivo) possessed antifungal activity against Candida albicans NBIMCC 72 and Candida glabrata NBIMCC 8673 (14 and 20 mm diameter of inhibition zones and MIC 10 mg/mL, respectively). The methanol and ethanol extracts from in vitro propagated plants had a broader spectrum of antibacterial activity than those from in vivo plants. All tested flower extracts possessed antimicrobial activity.

Evidence strength: Entirely in vitro at this time. No clinical trials have assessed antimicrobial effects of L. album preparations in humans.

5.3 Antioxidant Activity

In vitro / comparative evidence: A study of six Lamiaceae, including Lamium album, Lamium purpureum, and Galeopsis speciosa (commercial dried herb, methanolic extracts), used three in vitro antioxidant assays. Results for each plant varied between the tests, but Lamium album came out well in all three. Results revealed significant antioxidant activity, confirming that Lamium album has high potential for use in phytomedicine. Its methanol extract previously showed antioxidant activity in vivo via Caenorhabditis elegans model, owing to its richness in flavonoids and phenylpropanoids.

Evidence strength: Multiple in vitro assays and one in vivo invertebrate model (C. elegans) support antioxidant potential. Human clinical evidence is absent.

5.4 Antiviral Activity

In vitro evidence: A phytochemical study of the aqueous extract of the flowering tops of Lamium album led to identification of the antiviral iridoid isomers lamiridosins A and B. These compounds significantly inhibited hepatitis C virus entry (IC₅₀ 2.31 µM) in vitro. Studies of 14 iridoid analogues showed that while the parent iridoid glucosides demonstrated no anti-HCV entry activity, the aglycones of shanzhiside methyl ester, loganin, loganic acid, geniposide, verbenalin, eurostoside, and picroside II exhibited significant anti-HCV entry and anti-infectivity activities.

Evidence strength: Preliminary in vitro findings only. No clinical or animal model studies have translated these results to therapeutic recommendations.

5.5 Anticancer / Antiproliferative Activity

In vitro evidence: The A549 human cancer cell line and normal kidney epithelial cells MDCKII were used in assessing the anticancer effect of L. album plant extracts. Various in vitro and in vivo model systems were used to reveal antiviral, antibacterial, antioxidant, anticancer, cytoprotective, wound-healing, and other significant pharmacological effects. It should be noted, however, that some of the pharmacological effects occur at considerably high concentrations and therefore need to be treated with caution.

Evidence strength: Preliminary in vitro and isolated in vivo model data only. There is no human clinical evidence for anticancer applications.

5.6 Wound Healing

In vitro evidence: Methanol, ethyl acetate, and heptane extracts of Lamium album L. were tested for toxicity or ability to stimulate growth of human skin fibroblasts (HSF) in vitro. The biological effect depended on HSF cell density and on the kind and concentration of extract used. At a density of 1×10⁵ HSF cells/mL, no cytotoxicity of extracts was observed during 24 h of incubation. At a concentration of 25 µg/mL, cells remained intact. When cells were incubated with the heptane extract, there was relatively high viability (>60%) of cells and significant, gradually increasing mitochondrial dehydrogenase activity, measured by MTT assay. Stimulation of human skin fibroblast proliferation by the heptane extract of Lamii albi flos may indicate usefulness for wound healing in vivo and prospects for use in designing new medicinal plant preparations.

Evidence strength: In vitro cell culture models only. No controlled clinical trials have been conducted on wound healing with L. album flower preparations specifically.

5.7 Atopic Dermatitis — Human Clinical Trial

White dead nettle has been used in randomized controlled trials, but the results do not help in formulating recommendations. In a randomized, placebo-controlled trial in Israel, 49 patients with atopic dermatitis were treated for 2 weeks with a proprietary product containing Lamium album, Achillea millefolium, and Eleutherococcus senticosus (dried herb, ethanolic extracts). Patients were monitored for 8 weeks and assessed using the SCORAD scale; 44 people completed the trial. Improvement was similar for the treatment and placebo groups and was maintained after the active treatment period.

The conclusion of this trial was that treatment with the tri-herbal combination for atopic dermatitis does not differ from treatment with placebo. The trial is of interest because there was a significant response to both the treatment and the placebo; details of the placebo were not reported.

Evidence strength: One small double-blind, placebo-controlled, randomized trial (n = 49) using a multi-herb combination — not L. album alone — showed no significant advantage over placebo. The use of a combination product prevents attribution of any effect to L. album specifically. This is currently the most rigorous available clinical evidence, and it is negative.

5.8 Rheumatism and Arthritis

As for the Lamium genus, the evidence that some species can provide benefits in the treatment of rheumatoid arthritis is quite weak and is mostly speculative, based on the antioxidant and anti-inflammatory properties of L. album. In a second randomized controlled trial relevant to the genus, white dead nettle was used as the placebo in a trial of urtication in arthritis (Randall et al., 2000) and proved not as inert as the designers had hoped, illustrating some of the problems of determining a placebo in trials of herbal medicines.

Evidence strength: No dedicated clinical trials exist for L. album in arthritis. Traditional use is documented but scientific support is weak and indirect.

5.9 Antifungal Activity (Fusarium)

A study aimed to evaluate the efficacy of L. album flower extracts in inhibiting in vitro growth and biosynthesis of mycotoxins by Fusarium culmorum and F. proliferatum strains. Extracts were obtained by supercritical fluid extraction using CO₂. Effects of concentrations of 2.5, 5, 7.5, and 10% were assessed on a potato dextrose agar medium. L. album flower extracts reduced mycelium growth by 0 to 30.59% for Fusarium species.

Evidence strength: In vitro food-safety application only. Not directly relevant to human therapeutic use.

6. Body Systems and Health Areas

• Respiratory system: Commission E-approved indications include catarrh of the upper respiratory tract and inflammation of the oral and pharyngeal mucosa.
• Female reproductive system: Traditional uses are especially prominent in menorrhagia, uterine hemorrhage, vaginal and cervical inflammation, and leucorrhoea.
• Integumentary system (skin): The drug is also used externally for superficial skin inflammations. Wound healing activity is supported by in vitro fibroblast proliferation data.
• Immune and inflammatory system: In vitro studies demonstrate inhibition of IL-8 and TNF-α release from human neutrophils by key constituents.
• Digestive system: White dead nettle contains bitter iridoid constituents responsible for its stimulating effect on digestion and support of liver function.
• Musculoskeletal system: The genus is used in folk medicine for hypertension, scrofula, paralysis, and rheumatic conditions. Scientific support remains weak.
• Antimicrobial defense: In vitro antibacterial activity demonstrated against clinical bacteria and some yeasts (Candida species).
• Antiviral: In vitro anti-HCV entry inhibition by lamiridosins A and B at IC₅₀ 2.31 µM.

7. Dosage Forms and Reported Dosages

According to Commission E, for internal use the daily dose of Lamii albi flos is 3.0 g; for external use it is 5.0 g. The drug is mostly used in the form of infusions or as a sitz bath (5.0 g per sitz bath).

In the one available randomized clinical trial, forty-nine patients were recruited for a two-week treatment to test the efficacy of a tri-herbal combination (including L. album as one of three herbs) on atopic dermatitis in a randomized, placebo-controlled trial. The medication was taken orally three times daily for two weeks. Specific doses of L. album alone within this combination were not separately reported.

In in vitro anti-inflammatory research, the level of cytokine production was assessed after incubation with the compounds at concentrations of 1–25 µM. These concentrations pertain to isolated compounds in cell culture and do not translate directly to clinical dosing guidance.

The HPLC–DAD method was developed and validated for the quantification of iridoids (lamalbid), phenolic acids/depsides (chlorogenic acid), phenylpropanoids (verbascoside), and flavonoids (rutin, quercetin malonylhexoside, tiliroside) in aqueous and ethanolic-aqueous extracts of Lamii albi flos, providing a basis for future standardization but not yet translating into standardized clinical dosage specifications beyond the Commission E recommendation.

8. Safety Considerations

General Toxicological Profile

Lamium album is classified as a non-toxic plant, and moderate consumption is considered compatible with breastfeeding. The Commission E Monographs for the herb classification state that pharmacological properties, pharmacokinetics, and toxicology are not comprehensively known.

In Vitro Cytotoxicity Data

In fibroblast cell culture studies, at a density of 1×10⁵ HSF cells/mL, no cytotoxicity of extracts was observed during 24 h of incubation. During 24–72 h of incubation with lower cell density (2×10⁴ HSF cells/mL), significant cytotoxicity was observed for methanol and ethyl acetate extracts at concentrations greater than 125 µg/mL, but at a concentration of 25 µg/mL the cells remained intact. This indicates that cytotoxicity is concentration-dependent and appears at levels considerably above typical exposure from herbal preparations.

Pharmacological Effects at High Concentrations

It should be noted that some of the pharmacological effects occur at considerably high concentrations and therefore need to be treated with caution.

Adulteration and Contamination Risk

Precautions with herbal teas in general include ensuring procurement from reliable sources, as poisoning may occur by confusion with other toxic plants, poisoning from heavy metals, or food poisoning due to contamination with bacteria or fungi.

Evidence Limitations and Overall Evidence Assessment

Even though Lamium album has been widely used both traditionally and currently, there is very little information on its efficacy. Most of the scientific evidence on the Lamium genus has been conducted through in vitro studies over the past 15–20 years. If in vivo studies conducted with herbs belonging to the Lamium genus are few, the RCT studies are even fewer. The sole completed RCT involving L. album used a multi-herb combination product and found no significant advantage over placebo for atopic dermatitis. No well-powered, single-herb, controlled clinical trials have been published for any indication.

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