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Linden

Scientific Name(s): Tilia cordata Mill., Tilia platyphyllos Scop.
Common Name(s): Basswood, European linden, Lime flower, Lime tree, Linden

Clinical Overview

Use

Linden has been used to induce sweating for feverish colds and infections, reduce nasal congestion, and relieve throat irritation and cough. Linden has sedative effects and has been used to treat nervous palpitations and high blood pressure. It has also been used in lotions for itchy skin. However, there is limited clinical information.

Dosing

Linden is available in several dosage forms. There are no recent clinical studies to support a specific dosage of linden. No more than 2 to 4 g/day of linden from teas or other preparations for internal use should be consumed. Similar dosage regimens can be found on various commercial Web sites.

Contraindications

Although no recent clinical data has been published, the German Commission E monograph concluded that the linden flower is cardiotoxic.

Pregnancy/Lactation

Avoid use due to the lack of data.

Interactions

None well documented.

Adverse Reactions

Reports exist of specific toxicity such as contact urticaria, allergy from certain Tilia fruit oils in rats, seasonal pollinosis, organochlorine pesticide residues in linden-containing beverages, and occupational contact dermatitis with rhinoconjunctivitis from soft wood dust exposure.

Toxicology

There is no documentation supporting the belief that old linden flowers may induce narcotic intoxication. References in the German Commission E report that frequent use of linden flower teas has been associated with cardiac damage.

Botany

The most common species of linden trees are T. cordata (small-leaved linden) and T. platyphyllos (large leaved-linden). They belong to the Tiliaceae family, which consists of nearly 80 species native to Europe and found in northern temperate regions. Linden trees are deciduous and fast growing, typically reaching 15 to 23 m in height and spreading 12 to 15 m wide. The 5-petaled, fragrant, yellow to white flowers are collected after spring bloom and are dried and preserved under low-moisture conditions. The leaves of the tree are heart-shaped, have serrate margins, and grow 5 to 10 cm long. Linden tree bark is smooth, gray, and fibrous. The flowers are the most valued medicinal components of the linden tree.1, 2

History

Since the Middle Ages, the flowers of the linden tree have been primarily used as a diaphoretic to promote sweating. They have also been used for a variety of other medicinal purposes in phytotherapy, including as an expectorant, diuretic, antispasmodic, stomachic, and sedative. In addition, the flowers have been used traditionally for the treatment of flu, cough, migraine, nervous tension, ingestion, various types of spasms, liver and gall bladder disorders, diarrhea, and elevated arterial pressure associated with arteriosclerosis. The linden flower is listed in the German Pharmacopoeia and is approved in the German Commission E monographs. In Germany, it is included in common cold and antitussive preparations, as well as in urological and sedative drugs. In German pediatric medicine, it is included with several other species as a diaphoretic component in a tea used to treat influenza.2, 3 The flavonoid, volatile oil, and mucilage components in linden may contribute to these claimed medical properties.4, 5

Homeopaths use linden for enuresis, incontinence, hemorrhage, prolapsed uterus, and epilepsy.6 Linden has been used for purported antidiabetic activity.7, 8

Infusions of the flowers make a pleasant-tasting tea. Several sources report that linden flowers were believed to be so effective in treating epilepsy that one could be cured simply by sitting beneath the tree.9, 10 Sugar is obtained from the sap of the tree, and the seed oil resembles olive oil.10 In Greek mythology, the nympha Philyra was transformed into a linden tree after begging the gods not to leave her among mortals.2

Chemistry

Linden has numerous medicinal constituents.4, 11 More than 24 additional minor components have been identified in the wood, flowers, and fruits of linden.12 Active ingredients in linden flowers include quercitin, rutin, kaempferol, volatile oils, mucilage, and other flavonoids.13, 14 The flavonoids and p-coumaric acid appear to be responsible for the diaphoretic (sweat-inducing) and antispasmodic properties of the plant. Other constituents include caffeic and chlorogenic acids, as well as the amino acids alanine, cysteine, cystine, and phenylalanine.

Volatile oil components (0.02% to 0.1%) include alkanes, esters, citral, eugenol, and limonene. Carbohydrates, such as arabinose, galactose, glucose, mannose, and xylose, are also present in the plant, as well as gum and mucilage polysaccharides (3%). The numerous tannins may account for the claimed chemotherapeutic properties of linden.12, 15 The ratio of tannins to mucilage appears to be important in determining the flavor of teas prepared from linden flowers. Teas with a 2% or greater tannin level and low mucilage content produce more flavorful teas. Flowers from T. cordata and T. platyphyllos contain relatively more tannin than mucilage.9

Uses and Pharmacology

Chemotherapeutic effects

Animal/in vitro data

Antiproliferative effects of T. cordata flower extracts have been evaluated.16 An aqueous extract of T. cordata flowers exhibited a stimulatory action on the proliferation of lymphocytes at concentrations ranging from 0.5 to 20 mg/mL. The Tilia extract exerted its stimulatory action on cell proliferation by acting as a partial agonist through peripheral benzodiazepine receptors.17 The immunomodulatory activity of coumarin scopoletin exhibits a cytostatic and cytotoxic effect on tumor lymphocytes.18, 19

Clinical data

Research reveals no clinical studies for the use of extracts of linden as a chemotherapeutic agent.

Relaxant/Antispasmodic

Animal data

Linden has sedative effects in animal models. A report documents isolation of a pharmacologically active benzodiazepine receptor ligand from Tilia tomentosa. Peritoneal administration of a flavonoid complex in mice produced an anxiolytic effect. Kaemferol binds to the benzodiazepine receptor but does not have any sedative or anxiolytic activity.11, 20, 21 Another study documented how freeze-dried aqueous extracts of linden, at doses ranging from 10 to 100 mg/kg, produced sedative effects in mice.22 In another study, both the hexane and methanol extracts of Tilia americana var. mexicana demonstrated anxiolytic and sedative effects in mice.23

Sedative properties may be associated with the volatile oil components citral, citronellal, citronellol, eugenol, and limonene.21 These effects were evident when mice inhaled oil from Tilia species.24 Other sedative effects include relief of sinus headache and migraines, as well as remedies for insomnia, stress, and panic disorder.

Linden has been used to treat nervous palpitations and has lowered high blood pressure brought on by stress and nervous tension in animal models.2 Linden extracts injected into rabbits caused vasodilation, which resulted in decreased diastolic arterial pressure leading to a hypotensive effect.25

Folk medicine has employed linden as an antispasmodic.4 Animal studies in vitro using rat duodenum have supported this claim. The activity was inhibited by atropine and papaverine and increased by acetylcholine. The antispasmodic properties are attributed to p-coumaric acids and flavonoids in the plant.

Clinical data

Research reveals no clinical studies for the use of extracts of linden as a chemotherapeutic agent.

Other uses

Bioadhesion was demonstrated in an assay on buccal membranes, which may account for linden's therapeutic use in relieving throat irritation and cough.26

An extract of Tilia species possessed in vitro antibacterial activity against organisms associated with stomatologic infections, and these extracts have been clinically useful.27 Lime flower has been reported to have antifungal activity.4 Linden may also have inhibitory activity against the growth of foodborne pathogens.28

Water extracts of various Tilia species have antioxidant activity. One study documents a dose-dependent antioxidant activity for Tilia argentea water extract.29, 30

Two main flavonoids, kaempferol and quercetin, in related T. argentea have potent anti-inflammatory activity at 50 mg/kg in a carrageenan-induced hind paw edema model in mice.31

The methanolic extract from the flowers of T. argentea exhibited hepatoprotective effects against d-galactosamine/lipopolysaccharide-induced liver injury in mice. Six flavonol glycosides were isolated from the methanolic extract through bioassay-guided separation procedures. Tiliroside was the principle flavonol glycoside and showed the most potent activity. Astragalin and isoquercitrin also possessed strong activity.32

Tilia has also promoted iron absorption in rats, which may be helpful in iron deficiency anemia.33

Dosing

Linden is available in several dosage forms, but there are no recent clinical studies to support a specific dosage. No more than 2 to 4 g/day of linden from teas or other preparations for internal use should be consumed.5

Pregnancy / Lactation

Avoid use due to the lack of toxicological data.

Interactions

None well documented. Linden contains vitamin K; however, at typical dosage regimens, linden should not interfere with warfarin or related anticoagulant therapy.25

Adverse Reactions

Many sources list few adverse reactions from linden. However, reports document specific toxicity such as contact urticaria34 allergy from certain Tilia species fruit oils in rats35 seasonal pollinosis36 organochlorine pesticide residues in linden-containing beverages37, 38 and occupational contact dermatitis with rhinoconjunctivitis from soft wood dust exposure.39, 40

Toxicology

There is no evidence to support the belief that old linden flowers may induce narcotic intoxication.9 References in the German Commission E document that the frequent use of linden flower teas has been associated with cardiac damage.5 This rare event suggests that linden teas should not be ingested by patients with a history of heart disease.5, 9, 10 Further review of medical literature reveals little toxicological data on linden.41

References

1. Tilia cordata. USDA, NRCS. 2017. The PLANTS Database (http://plants.usda.gov, December 2017). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Chevallier A. Encyclopedia of Medicinal Plants. New York: DK Publishing; 1996: 275.
3. Bisset NG, trans-ed. Herbal Drugs and Phytopharmaceuticals. Stuttgart, Germany: Medpharm Scientific Publishers; 1994;496-498.
4. Barnes J, Anderson L, Phillipson J. Herbal Medicines: A Guide for Healthcare Professionals. 2nd ed. London: Pharmaceutical Press; 2002:323-324.
5. Blumenthal M, ed. Herbal Medicine: Expanded Commission E Monographs. Boston, MA: American Botanicals Council; 2000.
6. Ivanova D, Gerova D, Chervenkov T, Yankova T. Polyphenols and antioxidant capacity of Bulgarian medicinal plants. J Ethnopharmacol. 2005;96:145-150.
7. Ashaeva L, et al. Farmatsiia. 1985;34:57-60.
8. Otoom SA, Al-Safi SA, Kerem ZK, Alkofahi A. The use of medicinal herbs by diabetic Jordanian patients. J Herb Pharmacother. 2006;6:31-41.
9. Tyler VE. The New Honest Herbal. Philadelphia, PA: GF Stickley Co.; 1987.
10. Duke JA. Handbook of Medicinal Herbs, Second Edition. Boca Raton, FL: CRC Press; 2003.
11. Toker G, Aslan M, Yesilada E, Memisoglu M, Ito S. Comparative evaluation of the flavonoid content in official Tiliae flos and Turkish lime species for quality assessment. J Pharm Biomed Anal. 2001;26:111-121.11451648
12. U.S. Department of Agriculture, Agricultural Research Service. 1992-2016. Dr. Duke's Phytochemical and Ethnobotanical Databases. Home Page, http://phytochem.nal.usda.gov/ http://dx.doi.org/10.15482/USDA.ADC/1239279
13. Kovac-Besovic EE, Spirtovic S. Comparison of flavonoid contents of Sambuci -, Verbasci -, and Tilia flos (MAPS-P-404). International Pharmaceutical Federation World Congress, Nice, France; August 31, 2002;62:132.
14. Buchbauer G. Lime-flower essential oil: analysis of aromatic substances. Dtsch Apoth Ztg. 1992;132:748-750.
15. Behrens A, Maie N, Knicker H, Kogel-Knabner I. MALDI-TOF mass spectrometry and PSD fragmentation as means for the analysis of condensed tannins in plant leaves and needles. Phytochemistry. 2003;62:1159-1170.12591272
16. Manuele MG, Ferraro G, Anesini C. Effect of Tilia x viridis flower extract on the proliferation of a lymphoma cell line and on normal murine lymphocytes: contribution of monoterpenes, especially limonene. Phytother Res. 2008;22(11):1520-6. PMID: 18688792
17. Anesini C, Werner S, Borda E. Effect of Tilia cordata flower on lymphocyte proliferation: participation of peripheral type benzodiazepine binding sites. Fitoterapia. 1999;70:361-367.
18. Manuele MG, Ferraro G, Barreiro Arcos ML, López P, Cremaschi G, Anesini C. Comparative immunomodulatory effect of scopoletin on tumoral and normal lymphocytes. Life Sci. 2006;79:2043-2048.16860346
19. Barreiro Arcos ML, Cremaschi G, Werner S, Coussio J, Ferraro G, Anesini C. Tilia cordata Mill. Extracts and scopoletin (isolated compound): differential cell growth effects on lymphocytes. Phytother Res. 2006;20:34-40.16397918
20. Viola H, Wolfman C, Levi de Stein M, et al. Isolation of pharmacologically active benzodiazepine ligands from Tilia tomentosa (Tiliaceae). J Ethnopharmacol. 1994;44:47-53.
21. Cauffield JS. Supplements used to treat sleep disorders. US Pharm. 2001;6:50-60.
22. Coleta M, Campos MG, Cotrim MD, Proenca da Cunha A. Comparative evaluation of Melissa officinalis L., Tilia europaea L., Passiflora edulis Sims. and Hypericum perforatum L. in the elevated plus maze anxiety test. Pharmacopsychiatry. 2001;34(suppl 1):S20-S21.11518069
23. Aguirre-Hernandez E, Martinez AL, Gonzalez-Trujano ME, Moreno J, Vibrans H, Soto-Hernandez M. Pharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice. J Ethnopharmacol. 2007;109:140-145.16930893
24. Buchbauer G, Jirovetz L, Jager W. Passiflora and lime-blossoms: motility effects after inhalation of the essential oils and of some of the main constituents in animal experiment. Arch Pharm. 1992;325:247-248.1530457
25. Abascal K, Yarnell E. Nervine herbs for treating anxiety. J Altern Complement Med. 2004;12:309-315.
26. Schmidgall J, Schnetz E, Hensel A. Evidence for bioadhesive effects of polysaccharides and polysaccharide-containing herbs in an ex vivo bioadhesion assay on buccal membranes. Planta Medica. 2000;66:48-53.10705734
27. Sucice G, Hodisan V, Ban I, Chiorean V, Pop D. Pharmaceutical preparations from plant products employed in stomatologic diseases [in Romanian]. Rev Chir Oncol Radiol O R L Oftalmol Stomatol Ser Stomatol. 1988;35:191-194.
28. Gonul S, Karapinar M. Inhibitory effect of linden flower (Tilia flower) on the growth of foodborne pathogens. Food Microbiol. 1987;4:97-100.
29. Proestos C, Chorianopoulos N, Nychas GJ, Komaitis M. RP-HPLC analysis of the phenolic compounds of plant extracts. Investigation of their antioxidant capacity and antimicrobial activity. J Agric Food Chem. 2005;53:1190-1195.15713039
30. Yildirim A, Mavi A, Oktay M, Kara AA, Algur OF, Bilaloglu V. Comparison of antioxidant and antimicrobial activities of tilia, (Tilia argentea Desf Ex DC), sage (Salvia triloba L.), and black tea (Camellia sinensis) extracts. J Agric Food Chem. 2000;48:5030-5034.11052773
31. Toker G, Kupeli E, Memisoglu M, Yesilada E. Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden). J Ethnopharmacol. 2004;95:393-397.15507365
32. Matsuda H, Ninomiya K, Shimoda H, Yoshikawa M. Hepatoprotective principles from the flowers of Tilia argentea (linden): structure requirements of tiliroside and mechanisms of action. Bioorg Med Chem. 2002;10:707-712.11814859
33. el-Shobaki FA, Saleh ZA, Saleh N. The effect of some beverage extracts on intestinal iron absorption. Z Ernahrungswiss. 1990;29:264-269.2080638
34. Picardo M, Rovina R, Cristaudo A, Cannistraci C, Santucci B. Contact urticaria from Tilia (lime). Contact Dermatitis. 1988;19:72-73.3180773
35. Cristescu E, et al. Farmacia. 1969;17:531-538.
36. Derbes V. The linden (Tilia) as a factor in seasonal pollinosis. J Allergy. 1941;12:502-506.
37. Fernandez N, Sierra M, Garcia JJ, Diez MJ, Teran MT. Organochlorine pesticide residues in black tea, camomile, and linden. Bull Environ Contam Toxicol. 1993;50:479-485.8467130
38. Lino CM, Silveira MI. Loss of organochlorine pesticide tesidues during the infusion processes of linden (Tilia cordata Mill.). J Agric Food Chem. 1997;45:2718-2722.
39. Jiang ZC, Su YL, Zhang J, Deng YF, Ma ZH, Dong OL. Study on micronucleus frequency in peripheral lymphocytes in workers of match factories. Biomed Environ Sci. 1994;7:150-153.7946011
40. Krakowiak A, Krecisz B, Pas-Wyroslak A, Dudek W, Kiec-Swierzynska M, Palczynski C. Occupational contact dermatitis with rhinoconjunctivitis due to Tilia cordata and colophonium exposure in a cosmetician. Contact Dermatitis. 2004;51:34.15291831
41. Romero-Jimenez M, Campos-Sanchez J, Analla M, Munoz-Serrano A, Alonso-Moraga A. Genotoxicity and anti-genotoxicity of some traditional medicinal herbs. Mutat Res. 2005;585:147-155.16005256

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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