• Clinical data 90%
  • Efficacy 80%
  • Security 70%
  • Toxicity 30%

Synonyms

T. cordata: T. europaea var. γ L., T. parvifolia Ehrl., T. microphylla Vent., T. microphylla Willd., T. ulmifolia Scop., T. silvestris Scop., Tilia platyphyllos, T. cordifolia Bess., T. europaea var. β L., T. grandifolia (Ehrh.), T. pauciflora Heyne

General appearance

The infl orescence is yellowish-green. The main axis of the infl orescence bears a linguiform bract, membranous, yellowish-green, practically glabrous, the central vein of which is joined to about half its length with the peduncle. Flowers are arranged in clusters of 3–7 on a stalked pendulous cyme (T. platyphyllos) or in clusters of 3–15 on a stalked erect cyme (T. cordata). The diameter of the fl owers is between 1 and 1.5 cm. Sepals are easily detached, oblong-ovate, greyish-green, up to 6 mm long; their abaxial surface is usually glabrous, their adaxial surface and their borders are strongly pubescent. The 5 spatulate or ovate, thin petals are yellowish-white, up to 8 mm long. They show fi ne venation and their borders are only sometimes covered with isolated trichomes. The numerous stamens are free and usually constitute 5 groups. The superior ovary has a pistil with a 5-lobate stigma. The fruits are nutlets, 2 mm in diameter. The cut drug consists of fragments of infl orescences with a diameter 0.5–20 mm.

Major chemical constituents

The major constituents of the dried infl orescences are fl avonoids (1–5%): chiefl y quercetin glycosides (rutin, hyperoside, quercitrin and 3-glucosyl-7-rhamnoside), and kaempferol glucosides (astragalin (kaempferol-3- glucoside), tiliroside (astragalin-6´´-p-coumaroylester), astragalin-3- glucosyl-7-rhamnoside, astragalin-3,7-dirhamnoside). A complex of mucilage (7–10%, particularly from the bracts, mainly arabino-galactans with some uronic acid units) is present. The mucilage is composed of 5 fractions dominated by d-galactose, l-arabinose, l-rhamnose and uronic acid, with smaller amounts of glucose, mannose and xylose. The essential oil (0.02–0.1%) contains farnesol and its acetate, linalool, geraniol, geranyl acetate, germacrene, 1,8-cineole, eugenol, camphor, carvone, citral, citronellol, limonene, kaur-16-ene and some 70 other identifi ed compounds; which gives the drug its characteristic faint odour, more pronounced in the fresh fl owers. The presence of phenolic acids (caffeic, p-coumaric and chlorogenic acids), scopoletin, tannins (approximately 2%, including the procyanidin dimers B-2 and B-4), leucoanthocyanidins, among others, has also been reported.

Medicinal uses

Uses supported by clinical data

No information was found.

Uses described in pharmacopoeias and well established documents

The Commission E approved the internal use of Tilia platyphylos for colds and cold-related coughs. The use of the fl owers as an antispasmodic and diaphoretic agent is indicated.

Uses described in traditional medicine

Flores Tiliae are used to treat insomnia. Traditionally, the fl owers have been used for treatment of migraine, hysteria, arteriosclerotic hypertension, circulatory disorders and swelling of the ankle (50–53), cardiovascular and digestive complaints. Flos Tiliae are also used in urinary infections, infl uenza and anxiety.

Pharmacology

Experimental pharmacology

Action on lymphocyte proliferation

The aqueous extract of Flos Tiliae (1.5 g dried fl owers in 20 ml of water) demonstrated stimulatory effects on lymphocyte proliferation in vitro. The test system consisted of suspensions of lymphoid cells, which were asepti cally removed from the lymph nodes of inbred mice; the fi nal concentration of cells in culture was 2 × 106 cells/ml. The extract was tested at concentrations ranging from 0.5 to 80 µg/ml; control cells were treated with saline solution. The lymphocyte proliferation effect was mimicked by Ro 5-4864, a specifi c agonist of the peripheral benzodiazepine receptor and by Pk 11195, an agonist/antagonist of the same receptor; these agents were used as reference standards at a concentration of 5 × 10-7 M. Maximum stimulation of 170% was observed at a concentration of 20 µg/ml (p < 0.05). The synergistic effect of the extract with Ro 5-4864 suggests that the extract exerted its stimulatory action on cell proliferation by acting as a partial agonist on peripheral-type benzodiazepine binding sites.

Antitumour activity

The antiproliferative action of various extracts: aqueous (1.5 g fl owers in 20 ml of water), dichloromethane (9 g fl owers in 200 ml of dichloromethane) and ethanol (9 g fl owers in 200 ml of ethanol) of Tilia cordata fl owers on BW 5147 lymphoma cells and non-tumour lymphocytes was investigated. All extracts (at different concentrations) showed a selective action on tumour cells, inducing apoptosis. In the case of normal lymphocytes, these extracts suppressed mitogen-induced proliferation. The aqueous, dichloromethane and ethanol extracts inhibited proliferation of tumour and non-tumour cells in a concentration-dependent manner. From EC50 values, the dichloromethane extract proved to be the most active: it showed the greatest inhibition of cell proliferation, as shown by the EC50 values for both tumour cells (4.84 µg/ml) and non-tumour cells (14.12 µg/ml) (p < 0.05). Scopoletin, the main component in the dichloromethane extract had an antiproliferative action on BW 5147 cells, suggesting that it may be at least partly responsible for the activity displayed by this extract.

Antimicrobial activity

An aqueous extract of a commercial sample of Flos Tiliae demonstrated weak antibacterial activity in vitro against Escherichia coli and Staphylococcus aureus at a median inhibitory concentration (MIC) of 1 mg/ml/ agar plate; Staphylococcus aureus strain Oxford at an MIC of 1.5 mg/ml; and against Bacillus subtilis at an MIC of 3.1 mg/ml. A methanol extract of the dried fl owers exhibited weak antifungal activity against Aspergillus niger in vitro at a concentration of 5 mg/ml/agar plate. A 10% aqueous extract of dried Tiliae fl owers demonstrated antiviral activity against infl uenza virus A2 (Manheim 57) in cell culture

Smooth muscle effects

An aqueous extract of Tiliae fl owers at a concentration of 0.08 g/ml produced a biphasic response in vitro, consisting of transient relaxation of rat duodenum followed by a constriction.

Toxicology

An infusion of Tiliae fl owers (1:10) was assayed for anti-genotoxicity using the somatic mutation and recombinant test in Drosophila melanogaster. The infusion demonstrated desmutagenic activity (100% inhibition) against hydrogen peroxide used as an oxidative genotoxicant. These results could possibly be explained by synergism between phenolic components of the infusion and the hydrogen peroxide due to the known ability of phenols to scavenge reactive oxygen.

Clinical pharmacology

Diaphoretic action

The diaphoretic action of Tiliae fl owers was investigated in an open controlled clinical trial in patients with uncomplicated catarrhal disease. Fifteen patients with catarrhal disease inhaled water vapour from a preparation made with two sachets of Tiliae fl owers in 500 ml of water. Inhalation was maintained for 10 minutes at 40–50 ºC. A control group of 15 patients inhaled vapour from coloured water. Fifteen minutes after inhalation all patients experienced a certain subjective relief with further improvement of their condition in the group that had inhaled the preparation of Tiliae fl owers. In the control group improvement was observed only for the fi rst 120 minutes, and after addition of other symptomatic treatment. In the authors’ opinion the inhalation of a preparation of Tiliae fl owers had an appreciable diaphoretic effect. As there was no statistical analysis of the data, an objective assessment of this investigation is not posible.

Adverse reactions

A case-report of occupational allergy in a 55-year-old woman has appeared in the scientifi c literature. The woman, a non-smoker, who was working as a cosmetician, had experienced recurrent itching and erythematous papulovesicular lesions on the backs of her hands for around 18 months, and had had a history of sneezing, nasal obstruction and watery eyes for some years when she came into contact with depilatory wax or fl owers of Tilia cordata. Clinical examination, as well as routine laboratory parameters, remained normal. Total immunoglobulin E was 13 084 IU/ml and skin-prick tests showed positive reactions to common environmental allergens – grass and tree pollens, and to fl owers. Specifi c immunoglobulin E antibodies for grass and tree pollens were negative. The results of patch tests with Tilia fl owers with a standard series and a series of plant allergens were positive. A bronchial challenge test was performed in an inhalation chamber for 30 minutes. In the fi rst stage, the patient was challenged with placebo (potato fl our); during the second stage (after 7 days), with depilatory wax that had been thermally activated, and after 14 days with dried fl owers. Following such exposures, clinical symptoms of rhinoconjunctivitis appeared, and were observed for 48 hours after the challenges. In addition, increases in eosinophil and basophil proportions in nasal lavage and tear fl uids were observed during the late phase of allergic reaction. A diagnosis of occupational allergy was made based on the positive results of the allergy tests, analysis of the clinical status and medical history, and the positive results of specifi c challenges (64). Over a 5-year period, 1790 paediatric outpatients were observed for suspected allergic symptoms and 371 children were given a skin prick test to check for responses to aeroallergens. Aeroallergen sensitization due to Tilia cordata was observed in 11.4% of the paediatric patients examined.

Contraindications

If signs of hypersensitivity reaction appear (contact dermatitis or rhinoconjunctivitis), Flos Tiliae must not be used again.

Warnings

No information was found.

Precautions

General No information was found

News and Journals

References 
1. USSR pharmacopoeia, 11th ed. Vol. 
2. Moscow, Meditsina, 1990. 2. European Pharmacopoeia, 5th ed. Strasbourg, European Directorate for the Quality of Medicines, 2005. 
3. British herbal pharmacopoeia. Bournemouth, British Herbal Medicine Association, 1996. 
4. Dragendorff G. Die heilpfl anzen der verschiedenen Völker und Zeiten. Ihre anwendung, wesentlichen bestandtheile und geschichte. 
Ein Handbuch für Arzte, Apotheker, Botaniker und Droguisten [The healing plants of various peoples and times. 
Their use, basic healing properties and history. A handbook for doctors, dispensing chemists, botanists and pharmacists]. Stuttgart, Ferdinand Enke, 1898. 
5. Armenian national formulary for herbal medicines. Yerevan, Drug and Medical Technology Agency, Ministry of Health of RA JSC, 2001.etc